Policy and Medicine

May 2013 Update on Medical Innovation

 As the weeks go by, we try to collect stories and news coverage regarding physician-industry collaboration and the breakthroughs and successes that come from such relationships.  Below is a short summary of some recent physician-industry-academic-government collaborations and the impact they have had on individual patients, the U.S. healthcare system, and beyond.

In light of the recently proposed budgets for FY 2014, numerous scientific and medical groups have urged Congress and the Obama Administration to increase funding for research.  The Pharmaceutical Manufacturers and Researchers of America (PhRMA) recently noted that its member companies have invested approximately $550 billion since 2000 in the research and development of new therapies for a wide range of diseases such as diabetes, heart disease and HIV/AIDS.  PhRMA members alone invested an estimated $49.5 billion in 2011 in discovering and developing new medicines.

Diabetes

In mid-February of this year, NIH announced that “More people are meeting recommended goals in the three key markers of diabetes control, according to a study conducted and funded” by NIH and CDC. 

The report, published online February 15 in Diabetes Care, shows that, from 1988 to 2010, the number of people with diabetes able to meet or exceed all three of the measures that demonstrate good diabetes management rose from about 2 percent to about 19 percent.  Each measure also showed substantial improvement, with over half of people meeting each individual goal in 2010.

Improved cholesterol control was likely due to the increase in the use of statins, a type of cholesterol-lowering drug, from about 4 percent of people with diabetes during 1988-1994 to 51 percent during 2007-2010.  Glucose control was worse in Mexican-Americans and in younger adults.  Only 44 percent of Mexican-Americans met A1C goals, versus 53 percent of whites and blacks in 2007-2010 data. People between 20-49 years old were less likely to meet A1C goals than older people.

On Friday, March 29, 2013, FDA approved Invokana (canaglifozin) tablets, used with diet and exercise, to improve glycemic control in adults with type 2 diabetes. Type 2 diabetes is the most common form of the disease, affecting about 24 million people and accounting for more than 90 percent of diabetes cases diagnosed in the United States. Over time, high blood sugar levels can increase the risk for serious complications, including heart disease, blindness, and nerve and kidney damage.

“Invokana is the first diabetes treatment approved in a new class of drugs known as sodium-glucose co-transporter 2 (SGLT2) inhibitors,” said Mary Parks, M.D., director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research. “We continue to advance innovation with the approval of new drug classes that provide additional treatment options for chronic conditions that impact public health.”

Invokana, manufactured by Janssen Pharmaceuticals, a Johnson & Johnson company, works by blocking the reabsorption of glucose by the kidney, increasing glucose excretion, and lowering blood glucose levels in diabetics who have elevated blood glucose levels. Its safety and effectiveness were evaluated in nine clinical trials involving over 10,285 patients with type 2 diabetes. The trials showed improvement in hemoglobin A1c levels (a measure of blood sugar control) and fasting plasma glucose (blood sugar) levels.

The FDA is requiring five postmarketing studies for Invokana: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the Pediatric Research Equity Act (PREA), including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study.

Rare Diseases

National Institutes of Health (NIH) Director Francis Collins recently wrote in a blog post about Alex Barton, a recently turned 17-year-old boy, who was born with Neonatal-Onset Multisystem Inflammatory Disease (NOMID).  NOMID is the most severe form of an autoinflammatory disease spectrum called Cryopyrin-Associated Periodic Syndromes (CAPS). In 2001, researchers discovered the cause: a genetic mutation in a gene called NLRP3, which makes a protein called cryopyrin. Cryopyrin is part of a sensor in white blood cells that detects bacteria, harmful chemicals, and proteins produced by stressed, damaged, or dying cells. When the sensor detects these danger molecules, it launches an inflammatory response by activating a potent inflammatory protein called interleukin-1β.

When Alex came to the NIH in 2003 at age six to participate in a clinical trial, he was covered in a head to toe rash, had partial hearing loss, vision problems, and couldn’t walk.  Dr. Raphaela Goldbach-Mansky, a rheumatologist at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, launched a clinical trial together with other NIH specialists to test a drug called anakinra (Kineret^®), which the FDA had approved for rheumatoid arthritis (RA). Anakinra hadn’t been very effective for RA, but Goldbach-Mansky knew its mechanism should allow it to block cells from responding to IL-1β, curbing the inflammation that was destroying Alex’s body.

Just a few hours after Alex got his first injections of anakinra, the rash disappeared. Six days later, Alex was back on his feet and walking out of the NIH Clinical Center, where he recently came back to visit for his 10-year checkup. Goldbach-Mansky says that the results are truly astonishing. Of the estimated 80 or so children with NOMID in the United States, 53 are in her clinical trial on the NIH campus. Many of these patients were in such severe pain that they needed daily pain medication to sleep. After just a couple days of anakinra injections, these children were pain-free.

Based on Goldbach-Mansky’s trial data, the FDA approved the use of anakinra for NOMID. Collins noted that “anakinra and other related drugs are now also being tested for conditions like gout, type 2 diabetes, and heart disease—diseases that also involve inflammation and that together affect tens of millions of people nationwide. If IL-1β triggers inflammation in these diseases, as it does in NOMID, then anakinra and other IL-1β blockers might prove to be an effective treatment.”

HIV/AIDS

Back in early March of this year, NIH announced that “A two-year-old child born with HIV infection and treated with antiretroviral drugs beginning in the first days of life no longer has detectable levels of virus using conventional testing despite not taking HIV medication for 10 months, according to findings presented today at the Conference on Retroviruses and Opportunistic Infections (CROI) in Atlanta.”

This is the first well-documented case of an HIV-infected child who appears to have been functionally cured of HIV infection — that is, without detectable levels of virus and no signs of disease in the absence of antiretroviral therapy.  Further research is needed to understand whether the experience of the child can be replicated in clinical trials involving other HIV-exposed children, according to the investigators.  The case study was presented at the CROI meeting by Deborah Persaud, M.D., associate professor of infectious diseases at the Johns Hopkins Children’s Center in Baltimore, and Katherine Luzuriaga, M.D., professor of pediatrics and molecular medicine at the University of Massachusetts Medical School in Worcester. These two pediatric HIV experts led the analysis of the case.

In July 2010, the child was born prematurely in Mississippi at 35 weeks, to an HIV-infected mother who had received neither antiretroviral medication nor prenatal care.  Because of the high risk of exposure to HIV, the infant was started at 30 hours of age on liquid antiretroviral treatment consisting of a combination of three anti-HIV drugs: zidovudine, lamivudine, and nevirapine. The newborn’s HIV infection was confirmed through two blood samples obtained on the second day of life and analyzed through highly sensitive polymerase chain reaction (PCR) testing. PCR tests conducted on separate occasions that indicate the presence of HIV in an exposed infant are considered to have confirmed the diagnosis of infection. 

The baby was discharged from the hospital at 1 week of age and placed on liquid antiretroviral therapy consisting of combination zidovudine, lamivudine and co-formulated lopinavir-ritonavir. This drug combination is a standard regimen for treating HIV-infected infants in the United States.

Today, the child continues to thrive without antiretroviral therapy and has no identifiable levels of HIV in the body using standard assays.  The child is under the medical care of Hannah Gay, M.D., a pediatric HIV specialist at the University of Mississippi Medical Center in Jackson. Researchers will continue to follow the case.  “This case suggests that providing antiretroviral therapy within the very first few days of life to infants infected with HIV through their mothers via pregnancy or delivery may prevent HIV from establishing a reservoir, or hiding place, in their bodies and, therefore, achieve a cure for those children,” said Dr. Persaud.

In related news, NIH announced that “For children who have had HIV-1 infection since birth, the combination drug therapies now used to treat HIV appear to protect against the heart damage seen before combination therapies were available, according to researchers in a National Institutes of Health network study.”

In the early 1990s, children with HIV were not treated with anti-HIV therapy or were treated with only one drug. In recent years, children, like adults, have been treated with combinations of three or more anti-HIV medications. This combination approach is called highly active antiretroviral therapy, or HAART.  Before the widespread use of HAART, many children with HIV had chronic heart disease. In fact, heart failure was the underlying cause of death for 25 percent of HIV-infected children who died after age 10.

"We know that before today's robust treatments were available, HIV-positive children were more likely to have heart infections and inflammation; many also died from heart failure," said Dr. Lipshultz. "This research followed a rigorous protocol, and the findings suggest that HAART, in addition to being good for treating HIV, does not appear to adversely affect the heart’s function."

Parkinson’s Disease

Lastly, the Michael J. Fox Foundation recently announced a $1 million grant to Addex Therapeutics, a Swiss-based company, to help fund continued human clinical testing of dipraglurant for the treatment of Parkinson’s disease levodopa-induced dyskinesia (PD-LID) this morning. The Fox Foundation has been a pioneer in funding research for an effective treatment for levodopa-induced dyskinesia, as this is an area of significant unmet need for PD patients and could greatly improve the quality of patients’ lives. The Foundation has invested more than USD $26 million in dyskinesia-targeted research to date.

“Dyskinesia is a top priority for our Foundation because of its significant negative impact on patients' quality of life," said Todd Sherer, Ph.D., Chief Executive Officer of The Michael J. Fox Foundation.  “Candidates such as dipraglurant and other innovative therapies in development offer the possibility of improved quality of life through better symptomatic treatment of Parkinson’s. Dipraglurant targets a molecular mechanism that our Foundation has been investing in since 2005 and we are pleased to take part in its continued progress to the clinic.  We are enthusiastic about funding this work and hopeful that it may offer patients relief from a longstanding issue with the treatment of their disease.”

 “We are extremely pleased to receive this grant from The Michael J. Fox Foundation supporting the further development of dipraglurant,” said Bharatt Chowrira, Ph.D., Chief Executive Officer of Addex Therapeutics. “We believe the successful completion of the Phase 2a study offers some promise that dipraglurant has the potential to significantly change both the way patients are treated as well as their quality of life.  The work we will be able to pursue with this grant is critical to our continued advancement of this important approach to the treatment of PD-LID. Ultimately, we hope to see dipraglurant become the first drug to alleviate all PD-LID symptoms.”

Dipraglurant is an oral, small molecule allosteric modulator that inhibits selectively the metabotropic glutamate receptor 5 (mGluR5), a Class C G-Protein Coupled Receptor (GPCR). Dipraglurant holds potential to be used in combination with levodopa or dopamine agonists, or as a standalone treatment for PD-LID, PD-related motor symptoms, dystonia, non-motor symptoms of PD and other movement disorders. Data from a Phase 2a showed that dipraglurant met the primary objective of the study by exhibiting a good safety and tolerability profile.

Dipraglurant also demonstrated a statistically significant reduction in LID severity with both 50 and 100 mg doses. Dipraglurant appears to reduce dystonia severity in addition to chorea, the two major LID components. In a double-blind, placebo-controlled study conducted in the US and Europe, the primary objective was to demonstrate safety and tolerability in PD-LID patients. In addition, the trial was designed to evaluate exploratory efficacy as a secondary objective. Efficacy was measured using the modified Abnormal Involuntary Movement Scale (mAIMS), patient diaries documenting "off-time" (impaired voluntary movement), "on-time" (with or without dyskinesia) and sleep. The trial was supported by a grant from The Michael J. Fox Foundation for Parkinson's Research.

 

Twenty Academic Industry Alliances of 2012

Over the past few years, we have written about the critical partnerships that the pharmaceutical and medical device industries have created with academic medical centers and medical schools.  Most recently, we wrote about a partnership between Novartis and the University of Pennsylvania to bring to market a new approach to fighting cancer that has shown promising results in early trials.

Previously, we wrote about a new drug research collaboration was announced between pharmaceutical giant Pfizer and the University of California San Diego, which could deliver up to $50 million to local scientists over the next five years, speed the delivery of promising therapies to patients and help refill the fast-depleting pipeline of the world’s largest pharmaceutical manufacturer.   

Earlier this year, Merck announced a collaboration to create the California Institute for Biomedical Research (Calibr), an independent, not-for-profit organization--501(c)(3).   We have also written several times about the University of California, San Francisco Chancellor Susan Desmond-Hellmann, who advocates for establishing closer relationships with industry in order to spark new ideas, fund research, access high-tech equipment and speed medical advances to patients.   

 Consequently, FierceBiotech recently ran a story describing 20 Major Pharma-Academic Alliances in 2012.  We located descriptions of most of these alliances and provided background and links.  It is interesting that many of the alliances are with institutions outside of the United States including Australia, Canada, Germany, Hong Kong, Singapore and the UK 

UCSF and Sanofi  

The University of California, San Francisco (UCSF) has signed an alliance with Sanofi to share expertise in diabetes research and identify drug targets that could lead to new therapies for both type 1 and type 2 diabetes.  The $3.1 million collaboration will bring together scientists in three UCSF labs with deep understanding of the biology of beta cells – insulin-producing cells that are destroyed in type 1 diabetes and often produce too little insulin in type 2 – with Sanofi researchers who are experienced in developing potential drug candidates into actual therapies. 

The alliance is the University’s third collaboration with Sanofi, alongside brain trauma and oncology research launched last year, since the two signed a master agreement in January 2011 to work together in translating academic science into potential new therapies. Master agreements lay out the fundamental terms of research collaborations, align with the University's academic mission including broad publication rights, and form part of a core strategy for the UCSF Office of Innovation, Technology and Alliances to expedite that “bench-to-bedside” research. 

The University of Queensland, Australia and Johnson & Johnson  

Johnson & Johnson and the University of Queensland will co-develop drugs using components of spider venom as a treatment for chronic pain.  The maker of Ultram painkillers will work with Queensland’s Institute of Molecular Bioscience drug development program, the university said in a statement. Financial terms of the 12-month project were not disclosed.  Spider venoms have peptides that may “substantially reduce or block the pain,” Richard Lewis, professor at the institute, said in a phone interview. 

The University of Hong Kong, National University of Singapore, Pfizer, Lilly and Merck 

Scientists at the Genome Institute of Singapore (GIS) have unraveled the mechanism that causes liver cancer (hepatocellular carcinoma, HCC), one of the most common solid tumors worldwide. This genome-wide research was done in collaboration with colleagues from the National University of Singapore (NUS), University of Hong Kong, Eli Lilly & Co. USA, Merck Research Laboratories USA, Pfizer Oncology USA and Beijing Genomics Institute China 

Novo Nordisk and the University of Oxford 

Departing from its core competence, diabetes, Danish insulin giant Novo Nordisk (NOV: N) and the Kennedy Institute of Rheumatology at Oxford University have entered into a new partnership to develop promising new drug candidates and identify novel biomarkers and treatment targets for rheumatoid arthritis and other autoimmune inflammatory diseases.  Novo Nordisk will fund 10 Oxford researchers at the Kennedy Institute of Rheumatology to work within the partnership. A Joint steering committee with members from both parties, including Per Falk and Prof Feldmann, will oversee the partnership and assess research proposals from scientists at both organizations. 

University of Oxford and UCB 

The University of Oxford and UCB have signed a partnership worth £3.6M to work together on cutting-edge pharmaceutical research projects. The new collaboration will see scientists from industry and academia working together to develop innovative medicines to treat serious diseases in the areas of immunology and neurology. 

Novo Nordisk and the Juvenile Diabetes Research Foundation (JDRF) 

To address the underlying autoimmune process that is central to type 1 diabetes (T1D), JDRF and Novo Nordisk are partnering to discover and develop novel immunotherapies to prevent, treat, and help cure the disease.  Type 1 diabetes occurs when the body's immune system attacks and destroys the glucose-responsive, insulin-secreting beta cells of the pancreas, resulting in a lifetime requirement of insulin replacement therapy.  The collaboration between JDRF and Novo Nordisk will focus on research originating from academia and biotechnology companies, as well as from internal research projects at Novo Nordisk. 

Bristol-Myers Squibb and Vanderbilt University 

Vanderbilt University and Bristol-Myers Squibb Company announced a collaboration agreement for the discovery, development and commercialization of novel therapies acting on the mGluR4 glutamate receptor, known as positive allosteric modulators or PAMs, for the treatment of Parkinson’s disease.  Under the collaboration, the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD) will identify drug candidates from its existing program, which obtained major support from The Michael J. Fox Foundation for Parkinson’s Research (MJFF). Bristol-Myers Squibb will have the right to develop and commercialize products resulting from the collaborative research program.  

Under the terms of the agreement, Vanderbilt University will receive an upfront payment and multi-year research funding to continue to discover additional compounds. Vanderbilt is eligible to receive milestones and royalties based on developmental success and worldwide sales of the drugs emerging from the collaboration.  “The long-term commitment of and collaboration with the MJFF were critical to advancing this program to the stage where it is now perfectly positioned to work closely with Bristol-Myers Squibb for further development,” said P. Jeffrey Conn, Ph.D., VCNDD director and Lee E. Limbird, Chair in Pharmacology. “Partnering with Bristol-Myers Squibb is a real win for Vanderbilt and for Parkinson’s patients.”  

Novartis and the University of Pennsylvania 

See our story linked above in the introduction. 

Sanofi, Brigham and Women’s Hospital, and Harvard Medical School 

Sanofi SA, the French drug giant that bought Cambridge-based Genzyme Corp. for $20.1 billion last year, announced a new research collaboration with Brigham and Women’s Hospital, a teaching and research affiliate of Harvard Medical School.  The collaboration is focused on the immunology of type 1 diabetes.  Under the terms of the agreement, researchers from both organizations will undertake studies for a novel approach to treat type 1 diabetes. Sanofi has an option to exclusively license intellectual property emerging from this collaboration.  

Merck and California Institute for Biomedical Research 

Merck announced that it is putting $90 million over the next seven years into a new nonprofit biomedical research institute in San Diego called the California Institute for Biomedical Research (Calibr). The new institute will be led by Peter Schultz, the prominent chemist and biotech entrepreneur at The Scripps Research Institute, who previously ran The Genomics Institute of the Novartis Research Foundation.  The driving concept of the institute is different than just being a branch of Merck’s $8.5 billion global R&D enterprise. By remaining at arm’s length, the company can put in some of its own money, and allow researchers to amplify it with other grant support from academic collaborators. Once a project has reached “preclinical proof of concept,” Merck then has the option to swoop in to in-license drug candidates for further development. 

GlaxoSmithKline and Yale University  

GlaxoSmithKline (GSK) and Yale University will partner to design a new class of molecules to target disease-causing proteins.  This is the latest in a string of deals between Yale’s academic researchers and global pharmaceutical companies.  Under the agreement, the company is granted first chance to license promising protein-destroying drug candidates discovered in a research collaboration between GlaxoSmithKline and the laboratory of Craig Crews, the Lewis B. Cullman Professor of Molecular, Cellular, and Developmental Biology, and professor of chemistry and of pharmacology at Yale. 

The deal comes on the heels of other agreements signed by Yale with Gilead Sciences Inc., which is working with Yale to identify novel cancer therapeutics, and with Johnson & Johnson, which is also interested in drug candidates being developed at Yale’s West Campus. 

AstraZeneca and Broad Institute 

AstraZeneca and the Broad Institute in Cambridge, Massachusetts announced a collaboration to identify new chemical compounds targeting bacterial and viral infections that could speed the development of new antibacterial and antiviral drugs.  Under the agreement, screening and hit-to-lead chemistry will take place in the Broad’s Chemical Biology Platform and AstraZeneca will optimize, develop and commercialize potential compounds from identified, high-quality leads. 

Pfizer, AZ, Janssen, J&J, Boehringer Ingelheim, GSK, Merck, and the University of Dundee 

The five pharma’s will provide £14.4 ($23.1) million to fund a research consortium at the university for an additional four years.  The Division of Signal Transduction Therapy (DSTT) consortium, which was founded in 1998, is studying cell signaling and developing inhibitors of kinases and phosphatases to treat diseases such as cancer, arthritis and lupus. Pharmas share access to unpublished results, technology, reagents and first license to IP.  The DSTT includes 15 research teams based at the University of Dundee. Thirteen of the teams are based within the MRC Protein Phosphorylation Unit and Scottish Institute for Cell Signalling (SCILLS) at the College of Life Sciences. Together, consortium scientists will continue early-stage research in multiple areas, including cancer, arthritis, lupus, hypertension and Parkinson’s disease. 

Abbott, AZ, Lilly, Bayer, Sanofi, Merck, Texas A&M University, Cornell Medical School, and Bill & Melinda Gates Foundation 

Seven pharmaceutical companies have opened up compound libraries and agreed to share data with each other and the research institutions under the Gates Foundation's TB Drug Accelerator program. The program shifted last year to implementing assays and tools into a drug discovery effort from building the assays and tools. The foundation hopes to have proof-of-concept for a one-month, three-drug regimen within 10 years. The structures of lead compounds identified will be placed in the public domain. 

AZ, Genentech, Merck, and Washington University in St. Louis, School of Medicine 

Pfizer, Lilly, Roche, Servier, J&J, Janssen, and Kings College, London 

Five-year research project on autism to develop and validate translational research approaches for autism therapies and establish European clinical sites for autism trials. The project hopes to produce validated cellular assays, animal models, functional MRI (fMRI) methods, PET radioligands and biomarkers 

Accuray and Rupercht-Karls, Universitat Heidelberg 

Accuray Incorporated, the premier radiation oncology company, announced the signing of a multi-year master research and collaboration agreement with the University of Heidelberg, a luminary research institution located in Heidelberg, Germany that contributes to the city’s top international position in therapy, research and science. Accuray and the University of Heidelberg will collaborate on cutting-edge research in radiation oncology to advance treatment technology and provide health care professionals with the most advanced tools for treating patients. 

AZ, Washington University in St. Louis, School of Medicine, Cornell Medical School, The Feinstein Institute for Medical Research, and The University of British Columbia 

AstraZeneca and Dr. Steven Paul of Weill Cornell Medical College announced a first of its kind research alliance that brings four leading academic research laboratories together with AstraZeneca to study a major risk factor for Alzheimer’s disease, the apolipoprotein E4 genotype (ApoE). The newly established collaboration with AstraZeneca is called the A5 alliance.  The A5 alliance members represent a team of academic scientists with expertise in ApoE biology who will focus on identification, validation, and risk reduction of drug targets for treatment of Alzheimer’s disease.

President’s Council of Advisors on Science and Technology: Propelling Innovation in Drug Discovery, Development, and Evaluation

Due to biomedical innovations—including advances in medicines, medical procedures, and public health, life expectancy at birth has risen from around 47 years at the turn of the 20th century to 78 years today, and many diseases that were once fatal or debilitating can now be prevented, delayed, or ameliorated.   

In fact, pharmaceutical therapies have helped lead to vaccines that have eradicated or controlled many devastating infectious diseases including polio, small pox, and measles.  HIV is now treated with over 20 Food and Drug Administration (FDA)-approved drugs.  Multi-drug regimens effectively control HIV infection, preventing the development of AIDS.  Pharmaceutical therapies have led to cures for multiple malignancies that were once universally fatal; for example, childhood leukemia is now cured in 80 percent of cases, testicular cancer in over 90 percent of cases, and Hodgkin’s lymphoma in over 90 percent of cases.  Along with a reduction in smoking and better medical care, cholesterol-lowering therapy, blood-pressure-lowering drugs, anti-platelet agents, and diabetes treatment have contributed to a substantial decrease in death from heart attacks (70 percent decline over the past 60 years). 

A recent report recognized that in addition to academic researchers who “have unlocked secrets of basic biology and revealed mechanisms that underlie disease,” these innovations have been brought forth by a “a robust bio-pharmaceutical industry, which has developed molecules to treat disease and conducted clinical trials to demonstrate their efficacy.”  Despite this progress, challenges remain.   

To address these challenges, “The United States should set a goal of doubling the output of innovative new medicines that meet critical public health needs over the next 10 to 15 years, while continuing to increase drug safety,” a presidentially appointed council of experts advised in a report released in late September.  The council recommends a number of actions involving industry, academia, and the Federal Government.  

“While basic biomedical sciences have seen stunning progress in past decades, challenges remain in translating those scientific advances into practical solutions,” according to the report—Propelling Innovation in Drug Discovery, Development, and Evaluation—produced by the President’s Council of Advisors on Science and Technology (PCAST).  The report assesses the reasons for that long-term trend.  

To support innovation and accelerate the development of new therapies, the report makes a number of detailed recommendations aimed at  

• bolstering the discovery and development of new therapeutic compounds;
• optimizing processes used by the Food and Drug Administration (FDA) to evaluate the safety and efficacy of candidate drugs;
• enhancing long-term monitoring of approved medicines; and
• enhancing public understanding about the benefits and risks of medicines.  

“With improved collaboration among all the participants in the drug development ecosystem and optimization of drug-evaluation pathways, American researchers and companies should be able to accelerate the development of safe and effective drugs while also strengthening the U.S. economy,” said Eric Lander, who co-chairs PCAST.  

The report notes that heart disease and stroke remain leading causes of mortality, many common cancers are still incurable unless they are caught in the earliest stages, and the vast majority of rare diseases lack effective therapies altogether.  Infectious diseases, including those caused by antibiotic-resistant bacteria and viruses with pandemic potential, pose a constant threat of large-scale mortality. And treatments for psychiatric diseases, which impose a tremendous burden on society, are frustratingly limited in their efficacy, as are treatments for neurodegenerative diseases such as Alzheimer’s.  

All three major components of the drug development ecosystem—basic biomedical research in universities and research institutes, clinical research in hospitals, and drug discovery and development in the biopharmaceutical industry—are facing growing challenges as the time, complexity, and cost of developing drugs have gone up, the report states.  The rate of new-drug applications submitted by industry to the FDA, as well as new drug approvals, has remained relatively constant for 20 years.  In an encouraging sign, however, the FDA approved 35 new medicines in the past year—among the highest totals in the past decade. 

The report concludes there are two critical needs related to drug discovery and development that must be addressed to advance innovation:  

(1)  Scientists need better methodologies and tools for translating basic biological insights into validated therapeutic targets and leads—a gap in the drug discovery and development pipeline that academic scientists often view as “too applied” and pharmaceutical companies often eschew as “too basic” to justify private investment.  

(2) Pharmaceutical developers and regulators need to incorporate new efficiencies into clinical trials of candidate medicines—complex and costly human studies that today constitute fully 40 percent of the biopharmaceutical industry’s R&D budget.  

To achieve some of the report’s broader goals, PCAST recommends the creation of a public-private “Partnership to Accelerate Therapeutics,” involving representatives from the bio-pharmaceutical industry; the academic biomedical research and ethics community; physician societies and pharmacists; patient-focused research foundations and advocacy groups; healthcare providers and insurers; and the Federal Government. The Partnership would help identify and plan collaborative actions to speed drug development while balancing competing stakeholder interests and minimizing duplication of efforts.  

This report should be applauded for such a recommendation.  We have long praised industry collaboration, and with such a large and diverse group of stakeholders, we are hopeful that this report will lead to more progress and innovation.  The report recognized that “development of innovative medicines … remains essential for progress in the prevention and treatment of human disease.” 

In addition, the report concludes that the return on investment in certain disease domains may be too low to justify their pursuit by companies, even though the potential benefits for public health in these domains may be large.  It recommends that the Department of Health and Human Services (HHS) commission a study to assess potential mechanisms to encourage companies to tackle important medical challenges that may be financially unattractive.  

“There is a tremendous need for new antibiotics, for example, but the potential market share for such medicines is typically small and their duration of use is typically short,” said PCAST member Christine Cassel, a physician who—with Lander and PCAST members Ed Penhoet and Rick Levin—oversaw a group of 30 outside experts who helped inform PCAST in its work.

R&D Under Stress

The report recognized, contrary to some critics assertions, that there is evidence that industry R&D investment, a major component of this innovation ecosystem, is under significant stress: 

• The pharmaceutical industry is facing the largest “patent cliff” in its history: drugs with annual sales exceeding $200 billion will come off patent in the period 2010-2014, resulting in a loss of more than $100 billion in sales to generic substitutions; only a small fraction is expected to be replaced by new product revenues.
• Venture capital to start new biotechnology firms and fund innovative drug development activities appears to be declining, due not only to general economic conditions but to what are cited as concerns about unfavorable returns in the drug-innovation sector.
• Many companies are exiting important fields of critical public health need. For example, despite the growing health care and economic burden of neurodegenerative diseases, such as Alzheimer’s disease and psychiatric diseases, many major pharmaceutical companies are closing down or severely curtailing drug discovery programs. 

The report identified two critical areas related to drug discovery and development that must be addressed to advance innovation: 

1. 1.    Scientific knowledge gaps between basic research and commercial projects.
2. 2.    Inefficiency in clinical trials.  

The report also highlighted multiple issues and opportunities that relate to the evaluation of new drugs for approval:   

1. There are opportunities to accelerate the approval of a broader range of truly innovative drugs for patients who need them. Such acceleration should be supported by stronger tools for and enforcement of post-approval study 
2. The FDA requires methods to rapidly approve drugs for narrow populations for which there is a favorable benefit-risk balance, while protecting the broader population from drugs that have an unknown or unfavorable benefit-risk balance 
3. Stronger post-marketing surveillance and communication tools are needed to generate evidence on the benefits and risks of drugs and to communicate those benefits and risks to the public 
4. Innovators require greater clarity about general regulatory pathways for innovative products and approaches 
5. Innovators require greater consistency, efficiency, and communication with respect to their individual drug applications 

These recommendations are encouraging.  We have seen the pharmaceutical and medical device industry significantly maligned for their attempts to create wealth from medical products.  Reports like these go a long way to dispelling the myth that creating new products is easy and can cost as little as a million dollars.  The truth drug development is around $3 billion per new product which in the end may not be sustainable.  A little encouragement from the Whitehouse on the need for reduced regulations will go a long way to encouraging future investment.

Ten BioPharmaceutical Companies Launch TransCelerate BioPharm, Inc. to Accelerate Product Development

Ten leading biopharmaceutical companies announced that they had formed a non-profit organization to accelerate the development of new medicines. Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Pfizer, Genentech a member of the Roche Group, and Sanofi launched TransCelerate BioPharma Inc. ("TransCelerate") , the largest ever initiative of its kind, to identify and solve common drug development challenges with the end goals of improving the quality of clinical studies and bringing new medicines to patients faster. 

Each of these company’s should be applauded for their efforts to solve these very real problems.  As we noted last year, the “valley of death” for most companies developing drugs can be brutal.   

Through participation in TransCelerate , each of the ten founding companies will combine financial and other resources, including personnel, to solve industry-wide challenges in a collaborative environment.  Together, member companies have agreed to specific outcome-oriented objectives and established guidelines for sharing meaningful information and expertise to advance collaboration. 

“There is widespread alignment among the heads of R&D at major pharmaceutical companies that there is a critical need to substantially increase the number of innovative new medicines, while eliminating inefficiencies that drive up R&D costs,” said newly appointed acting CEO of TransCelerate BioPharma , Garry Neil, MD, Partner at Apple Tree Partners and formerly Corporate Vice President, Science & Technology, Johnson & Johnson. “Our mission at TransCelerate BioPharma is to work together across the global research and development community and share research and solutions that will simplify and accelerate the delivery of exciting new medicines for patients.” 

Other companies, including smaller ones, will be able to join, Mr. Neil said.  The companies will contribute money and personnel to work on the various projects.  While TransCelerate will have a headquarters in Philadelphia, the employees from different companies will not all work together at that location, instead meeting as necessary, Mr. Neil said. 

Members of TransCelerate have identified clinical study execution as the initiative's initial area of focus.  Five projects have been selected by the group for funding and development, including:  

1. Development of a shared user interface for investigator site portals,
2. Mutual recognition of study site qualification and training,
3. Development of risk-based site monitoring approach and standards,
4. Development of clinical data standards, and
5. Establishment of a comparator drug supply model. 

Forbes expanded on this list:

1. Creating clinical data standards, as with the case of notation of gender, so that all clinical trials note things like gender, changes in blood pressure, and such in the same way.
2. Standardizing the way that risk to patients is measured in studies, so that side effects are always handled in the same way.
3. Building a common Web site for doctors enrolling patients in clinical trials to use, so that each company isn’t running its own portal with a different look and feel.
4. Standardizing the process of training doctors and qualifying clinical trial sites, so that a physician doesn’t need to go through separate but similar training programs in order to work in clinical trials run by two companies.
5. Standardizing the process by which companies strike deals to do clinical trials that compare an experimental drug to a standard regimen made by another company. 

As shared solutions in clinical research and other areas are developed, TransCelerate will involve industry alliances including Clinical Data Interchange Standards Consortium (CDISC), Critical-Path Institute (C-Path), Clinical Trials Transformation Initiative (CTTI), Innovative Medicines Initiative (IMI), regulatory bodies including the US Food and Drug Administration (FDA) and European Medicines Agency (EMA), and Contract Research Organizations (CROs). 

Janet Woodcock, MD, director of FDA's Center for Drug Evaluation and Research, said, “We applaud the companies in TransCelerate BioPharma for joining forces to address a series of longstanding challenges in new drug development. This collaborative approach in the pre-competitive arena, utilizing the collective experience and resources of 10 leading drug companies and others to follow, has the promise to lead to new paradigms and cost savings in drug development, all of which would strengthen the industry and its ability to develop innovative and much-needed therapies for patients.” 

“These leading pharmaceutical companies are in a position to significantly influence changes in the way that clinical trials are done, so that better answers about the benefits and risks of drugs and other therapies are provided in a more efficient manner,” said Robert Califf, MD, Co-Chair of CTTI and Director of the Duke Translational Medicine Institute.  “This initiative is complementary to efforts of CTTI, and we look forward to working with TransCelerate BioPharma to improve the conduct of clinical trials.” 

TransCelerate BioPharma evolved from relationships fostered via the Hever Group, a forum for executive R&D leadership to discuss relevant issues facing the industry and solutions for addressing common challenges. TransCelerate was incorporated in early August 2012 and will file for non-profit status this fall. The Board of Directors includes R&D heads of ten member companies. Membership in TransCelerate is open to all pharmaceutical and biotechnology companies who can contribute to and benefit from these shared solutions. TransCelerate 's headquarters will be located in Philadelphia, PA.

Glen Giovannetti, Ernst & Young Global Biotechnology, Leader says today’s announcement encouraging because it is unique.  “We haven’t seen one quite like this before where 10 pharmaceutical companies paired up of sort of their own volition in a way,” he says. “They join other consortia. This seems to be more of a real commitment of their resources and their effort. I think it’s great. They’re going to concentrate on getting some standardization around the clinical trial process. Perhaps more important in the long term, how data is gathered and assembled it really could move toward greater standardization of data so that trial results downstream could be more easily pooled and shared and investigated for insights.”

Harvard and Pfizer Announce Industry-Academic Partnership

The collaboration between industry and academia has produced significant improvements in science and medicine for almost a century.  From the mid 1920’s when Frederick Banting and his assistant Charles Best isolated insulin in 1921 at the University of Toronto, academic-industry collaborations has led to tremendous breakthroughs that have saved and improved the health of millions. 

A new academic-industry partnership was recently discussed in an article in Bloomberg News.  The collaboration first began when Hal Dvorak, a Harvard scientist, helped spur the advance of targeted cancer drugs.  He then sought a partner to help him develop new treatments.  His partner—Pfizer, Inc.—is spending $100 million to open a state-of-the-art laboratory in Boston. For Dvorak, teaming with Pfizer “is an ideal arrangement,” he said, providing convenience and expertise bringing research into the clinic. 

“Pfizer, Sanofi, Merck & Co. (MRK) and other drug companies are putting a new twist on the arrangement by stepping up their level of collaboration with universities.  In the case of Pfizer, the world’s largest drug company is embedding operations in Boston, San Francisco, New York and San Diego, often in the very same buildings where famed academic institutions have labs. 

“No matter how much money you have, nothing compares to the innovation going on out in the world,” said Jose Carlos Gutierrez-Ramos, the director of the Pfizer lab, in an interview. “We want to be here, integrated into this fabric.” 

This new collaboration represents Pfizer’s future, as it sees uncertain times for its blockbuster drugs Lipitor and the painkiller Lyrica.  By establishing these academic relationships, Pfizer can “buy” promising ideas later down the road.  In two to three years, Pfizer plans to have 50 drug development projects running in their centers around the country, all of which have been opened since late 2010, Gutierrez-Ramos said. 

Part of these new collaborations come from the leadership of Pfizer Chief Executive Officer Ian Read, who has begun cutting back the size of the company, selling one non- pharmaceutical unit, planning to spin off another and trimming expenses.  He has said he wants to rebuild Pfizer into a smaller, faster-moving company that focuses on development of new drugs.  “It makes sense to outsource anything that someone else can do better than you and that you don’t consider a core competency or source of competitive advantage,” Erik Gordon, a professor of business at the University of Michigan in Ann Arbor, said in an e-mail. 

Pfizer is turning to executives like Gutierrez-Ramos, whose job is to create strong connections within one of the world’s most creative hotbeds for biotechnology innovation.  In Boston, the Pfizer lab is located in the same building as offices of renowned research centers of Boston Children’s Hospital and Beth Israel Deaconess Medical Center, which would make some potential partnerships just an elevator ride away. 

The Boston lab has reviewed 400 partnership proposals in the last year and is working on projects involving chronic kidney disease, osteoporosis and cancer, Tony Coyle, chief scientific officer for the Pfizer center, said in an interview.  Gutierrez-Ramos said he is trying to create an atmosphere at the lab where outside researchers easily come and go, and Pfizer’s scientists visit neighboring academicians on their turf. 

Pharmaceutical companies, which historically are highly secretive about their work because of competition, need to be willing to take more risks in the future, he said, creating access to its inner sanctums to develop drugs earlier. 

What Pfizer offers academic researchers are “extraordinary” resources for drug development that nearby university labs can’t match, said Harvard’s Dvorak.  Dvorak, in 1983, was one of the first scientists to demonstrate that cancer cells secreted vascular endothelial growth factor, or VEGF, the initial idea behind development of drugs, such as Roche Holding AG (ROG)’s Avastin, that cut off the blood supply to tumors to stop their spread. 

“An academic lab can only go so far,” Dvorak said in a telephone interview from Boston. “We’re good at identifying targets, but if you want to make monoclonal antibodies or take this to the clinic, we have no experience in that.  That’s not our bag.”   Coyle, of Pfizer’s center, agrees. “We’ve cured diabetes in mice so many times” in the laboratory, Coyle said. “But there’s been a very poor appreciation from the academic community” about how to develop drugs for use in the clinic. 

An example of the advantages for academics can be seen in a single machine located on the lab’s 18th floor.  Separated by a wall of glass from an open-plan suite for the group’s top managers, the machine has the ability to rapidly test thousands of compounds against Pfizer’s own chemical library to see if they match with known disease pathways or proteins that have been identified as possible targets.  Past rows of lab benches, two rooms full of complex imaging equipment are used to identify how proteins interact. 

Universities and research institutes need all the help they can get, according to a report by the Tufts Center for the Study of Drug Development released in April.  Funding from the U.S. National Institutes of Health has been unchanged for a decade, at about $31 billion for 2013.  At the same time, pharmaceutical companies have cut their early-stage research budgets in a tough economy to focus on late-stage clinical development and marketing, the report said. 

The partnership model now being pursued by Pfizer and a few other large drugmakers, “represents the most significant change in the innovative landscape we’ve seen in three decades,” said Ken Kaitin, director of the Tufts center.  “With academic centers, with the reduction in NIH support, there’s almost a desperation that they must, must find new revenue streams,” Kaitin said in an interview in Boston. “That, in most cases, means working with industry.”

Sanofi (SAN), based in Paris, has its own collaboration program, with Harvard, the University of California, San Francisco, and several others, the company said.  In March, Merck, the second-biggest U.S. drugmaker, announced it was joining the party.  The Whitehouse Station, New Jersey-based company said it will spend as much as $90 million over seven years to help fund a new California Institute for Biomedical Research it will run in San Diego. 

Ultimately, these companies and academic medical centers should be applauded for their collaboration and more partnerships such as these should be encouraged.  As the article recognizes, the tough economic times have resulted in less scientific grant money from the federal government and tighter budgets for pharmaceutical companies.  These partnerships have the promise of changing the current business structures of companies and finding new treatments and drugs that will cure chronic disease and help reduce health care costs.  Like the first collaboration that produced insulin over 90 years ago, these collaborations may be the ticket for curing diabetes and other serious illnesses.

The Office of the National Coordinator for Health IT: Using Real Time Data and Education to Prevent Prescription Drug Abuse

The Centers for Disease Control (CDC) has declared that the United States is in the midst of an epidemic of prescription drug overdose deaths. Deaths from prescription drugs now outnumber deaths from heroin and cocaine combined. Over the past decade, prescription drug-induced deaths have approached motor vehicle deaths as the leading cause of all injury deaths.  Programs that test collaborative efforts such as the PDMP will help identify best practices to help health care professionals combat prescription drug misuse at the moment of care. 

The Office of the National Coordinator for Health IT (ONC) recently announced the launch of a pair of pilots to test the effects of expanding state programs designed to prevent abuse of prescription drugs.  The pilots in Indiana and Ohio will find out how health IT (HIT) can help increase the effectiveness of prescription drug monitoring programs (PDMPs). 

PDMPs are statewide electronic databases that providers can use to identify and intervene with prescription drug abusers.  The databases collect, monitor and analyze electronically transmitted prescribing and drug dispensing data. 

Forty-nine states have these programs or have passed legislation authorizing them. However, the databases are not being used enough, according to the U.S. Department of Health & Human Services (HHS).  The ONC initiative is designed to increase providers’ real-time access to the data. 

“The PDMP pilot projects being launched today will help hospital staff identify a patient’s controlled substance history at the point of care to enable better targeting appropriate treatments and reduce the potential of an overdose or even death,” Farzad Mostashari, National Coordinator for Health IT, said in the announcement.”"We are not creating new systems, we are adding value to those that exist.” 

The Enhancing Access to PDMPs Project stems from joint efforts of public sector and private industry experts that participated in the White House Roundtable on Health IT and Prescription Drug Abuse in June 2011. In turn, the HHS Prescription Drug Abuse and Health IT Work Group of the Behavioral Health Coordinating Committee created the Action Plan for Improving Access to Prescription Drug Monitoring Programs through Health Information Technology. 

The project is funded by the Substance Abuse and Mental Health Services Administration (SAMHSA) and managed by ONC in collaboration with SAMHSA, the CDC, and the ONDCP. 

In the Indiana pilot, emergency departments will receive patients' controlled substance histories from the Regenstrief Medical Records System, a unit of the Wishard healthcare system that is also used by other area hospitals. In some states, the press release stated, EDs are responsible for almost 25 percent of controlled substance prescriptions. 

In the Ohio pilot, drug risk indicators will be included in the electronic health record at the Springfield Center for Family Medicine in Springfield, Ohio. The researchers will measure how that effects clinical decision making. 

The Enhancing Access to PDMPs Project grew out of a White House Roundtable on health IT and prescription drug abuse in June 2011. The project is funded by the Substance Abuse and Mental Health Services Administration (SAMHSA). ONC is managing it in collaboration with SAMHSA, the Centers for Disease Control and Prevention, and the Office of National Drug Control Policy. 

Under a New York bill recently passed by the state legislature, physicians will have to write electronic prescriptions for painkillers within three years and will also have to check online records before prescribing them. The measure mandates the creation of a database for controlled substances and requires pharmacists to report when they fill such prescriptions. 

Conclusion 

“Technology plays a critical role in our comprehensive efforts to address our nation’s prescription drug abuse epidemic,” said Gil Kerlikowske, director of National Drug Control Policy (ONDCP).  “Together with education, proper disposal practices, and enforcement, improving existing prescription monitoring programs is a priority for this administration.  We hope these innovative pilots will help usher in an era of ‘PDMPs 2.0’ across the nation to improve real time data sharing among, increase interoperability of data among states, and expand the number of people using these important tools.” 

As Kerlikowske recognized, “education” will play a key role in reducing prescription drug abuse.  Continuing medical education (CME) can offer a critical solution to offering healthcare professionals education. 

FDA: Food and Drug Administration Safety and Innovation Act (FDASIA) and Patient Focused Drug Development

Last week, President Obama signed into law the Food and Drug Administration Safety and Innovation Act (FDASIA). Among the numerous provisions contained in this Act are several provisions that will enhance and increase patient participation in medical product regulation.  Specifically, Sec. 1137 of the new law will allow the agency to develop and implement strategies to solicit the views of patients during the medical product development process and consider the perspectives of patients during regulatory discussions.  This will include: 

• Fostering participation of FDA Patient Representatives as Special Government Employees in appropriate agency meetings with medical product sponsors and investigators; and,
• Exploring means to provide for identification of FDA Patient Representatives who do not have any, or have minimal, financial interest in the medical products industry. 

Consequently, Theresa Mullin, Ph.D. Associate Director for Planning and Informatics FDA Center for Drug Evaluation and Research (CDER) recently gave a presentation on “Patient-Focused Drug Development.” 

Presentation 

Mullin first outlined FDA’s benefit-risk (B-R) framework, which looks at five (5) key considerations: 

1. Severity of Condition
2. Unmet Medical Need
3. Benefit
4. Risk
5. Risk Management 

Severity of Condition and Unmet Medical Need provide regulators with the clinical context for weighing benefits and risks and the associated uncertainties. 

Benefit and Risk incorporate expert judgments based on evaluation of the efficacy and safety data. 

Risk Management incorporates expert judgments on the expected impact of efforts to reduce and further characterize risks. 

Assessment of a drug’s benefits and risks involves analysis of severity of condition and current state of the treatment armamentarium.  Patients who live with a disease have a direct stake in drug review process and are in a unique position to contribute to drug development.  As a result, FDA noted that its review process could benefit from systematic approach to obtaining patient perspective on disease severity or unmet medical need. 

Mullins noted how FDASIA – the provisions reauthorizing the Prescription Drug User Fee Act (PDUFA) – provides resources to support additional program staff to expand activities dedicated to providing review divisions with patient input.  FDA will convene meetings with participation from review divisions, the relevant patient advocacy community, and other interested parties. 

FDA will hold four public workshops per year—a total of 20 meetings over 5 years.  Each meeting will focus on a different disease area, reviewing the armamentarium for that indication, and identifying areas of unmet need. 

Benefit‐Risk Assessment Framework: Analysis of Condition 

Assessing Evidence and Uncertainties– for a given drug for a given indication‐questions FDA considers include: 

• What is the treated (or prevented) condition?
• What are its clinical manifestations (i.e., symptoms that are either reported or observed)?
• What is known about the natural history and progression of the condition, including in specific subpopulations?
• How severe is the condition for those who have it?
• How does severity vary across the sub‐populations we have defined? (Note specific subpopulations and nature of differences.)
• What is the basis for our assessment of the condition and its severity? (Note any relevant literature, clinical experience, expert opinion, etc.)
• What are the major uncertainties in the available information? What are their implications? 

Benefit‐Risk Assessment Framework: Unmet Medical Need 

Assessing Evidence and Uncertainties –for a given drug for a given indication‐FDA considers: 

• What other pharmacological therapies are approved for this condition?
• How effective are these alternative therapies?
• How does their effectiveness vary by sub‐population?
• How well tolerated are these alternative therapies?
• How does tolerance vary by sub‐population?
• What off‐label pharmacological therapies might be considered?
• How effective and how well tolerated are they reported or believed to be?
• What non‐pharmacological therapies might be considered?
• How effective and how well tolerated are they reported or believed to be?
• What kinds of evidence are available about the use of alternative treatments for this condition?
• What is the strength of evidence in each case?
• What are the major uncertainties in the evidence? What are their implications? 

The presentation then discussed Patient‐Reported Outcome (PRO) Measures, which FDA defined as “any report of the status of a patient’s health condition coming directly from the patient, without interpretation by physicians or anyone, about how the patient functions or feels in relation to a health condition and its treatment.”  FDA reviews PRO instruments and looks at whether the instrument measures the concept it is supposed to measure.  FDA looks at whether the instrument is: 

• Well‐specified and reliable
• Specific for target population
• Specific for target indication
• Adequate measurement properties (e.g., content validity) 

The presentation then noted that qualitative research can be used to establish PRO content validity.  This might include: 

• Focus groups to generate a pool of patient outcome‐related domains and their components (e.g., What symptoms and functions or activities impacted by disease that are most important to patients)
• Surveys including a larger and more diverse sample patients with a given condition (e.g., examine the importance and relevance of domains identified by literature review, expert opinion or among a smaller set of patients, to validate these items and perhaps explore other measurement characteristics) 

Mullins then used the example of people with chronic pain.  Focus groups conducted with patients who experience chronic pain identified 19 aspects of their lives (outcome domains) that are significantly impacted by the presence of their symptoms and for which improvements were important criteria that they use in evaluating the effectiveness of any treatment. 

Next Steps Patient‐Focused Drug Development 

Throughout the rest of this summer, FDA will develop preliminary list of 20 disease areas for public comment to inform planning for the set of 20 PDUFA V meetings.  FDA will also develop a basic roadmap that could be used by patient groups interested in pursuing need for and development of PRO measures in a specific disease area.  This roadmap will identify important but currently unaddressed aspects of their disease experience to potentially be considered in evaluating new therapies. 

In September 2012, FDA will publish an FR notice with the preliminary list of 20 disease areas for public comment.  In October 2012, FDA will plan to hold public meeting to: 

• Discuss the proposed list of disease areas for the PDUFA meetings and get public input;
• Discuss strategies for getting broader public input and basic roadmap for identification of important patient outcomes and strategies for collaborative development PRO measures 

FDA Patient Representative Program 

The Patient‐Focused Drug Development initiative will also add to the existing FDA programs designed to integrate patients’ perspectives.  FDA’s patient advocacy programs are run by FDA’s Office of Special Health Issues.  One of their main programs is the FDA Patient Representative Program. 

Patient Representatives provide FDA with the unique perspective of patients and family members directly affected by serious or life‐threatening disease.  Patient Representatives serve in the several ways, including: 

• On Advisory Committees, where they offer the patient perspective, ask questions, and give comments to assist the committee in making recommendations.
• As consultants for review divisions –the clinicians and scientists who review data submitted to determine whether the product’s benefits outweigh the potential risks
• As presenters at FDA meetings and workshops on disease‐specific or regulatory and health policy issues 

The Programs activities include:

 

• Recruitment of New Patient Representatives
• Selection of Patient Representatives for:
  • Advisory Committees
  • Consultation with Review Division
  • Conducts Training For Patient Representatives
    • Individual FDA 101 Training
    • Monthly Webinars
    • Annual Workshop for Newly Recruited Patient Representatives 

In choosing Patient Representatives, FDA looks for someone who brings a personal viewpoint to the process and communicates a collective patient perspective.  A patient perspective is created when a person goes through personal experience with the disease.  A collective patient perspective is created when the person has knowledge of others’ disease experiences and conveys this collective patient perspective.

 Patient Representatives provide Advisory Committee and FDA insight on issues, problems, and/or questions pertinent to the viewpoint of patients and family members living with a specific serious or life‐threatening disease. 

• Personal experience with/knowledgeable about the specific illness
• Ability to articulate the perspective of patients
• Experience as a patient advocate
• Formal affiliation with a patient advocacy organization
• The ability to identify issues through communication with patient constituencies 

Patient Representatives serve on an Advisory Committee when a product or therapy related to specific illness is under review, as either voting or non‐voting member 

• Voting: must be appointed as special government employees (SGEs); requires disclosure of personal financial information to the FDA in order to determine whether their financial interests pose a possible conflict of interest on an advisory committee
• Non‐voting: may only vote on procedural matters concerning the conduct of the meeting
• In both cases: expected to provide the patient perspective, ask questions, and offer comments to assist the committee in making recommendations 

Drug Development Patient Consultant Program 

FDA also uses patients in its Drug Development Patient Consultant program.  This program incorporates the perspective of patient advocates into the drug development process; allows opportunity to participate in the FDA drug review regulatory process. 

Patients are selected to participate in meetings by matching a specific illness and proposed indication for the new therapeutic drug being developed.  Patients may participate in meetings (via telephone ) between the FDA and drug companies. 

The newly selected patient consultant receives training and participates in monthly telephone lecture series in preparation for these meetings.  To provide consultation to both FDA and the drug company, it is important that the patient consultant have background information on the drug under review.  About three weeks before each meeting, the patient consultant is mailed the meeting package containing the meeting issues and questions. The patient consultant reviews the meeting package in preparation for the meeting.

The National Dialogue for Healthcare Innovation: The State and Future of Physician-Industry Collaborations

 
The National Dialogue for Healthcare Innovation (NDHI) recently announced its inaugural event: the NDHI Summit on Physician-Industry Collaboration.  This summit, the first-of-its-kind, will include a cross-disciplinary dialogue on the issue of collaboration between physicians, industry, and other stakeholders in the U.S. healthcare ecosystem that drives innovation for the benefit of patients.  We previously wrote about NDHI last year and provided an update as well. 

NDHI was formed by the Healthcare Leadership Council, a coalition of chief executives representing all sectors of American healthcare, as an interactive forum where leaders from across the healthcare industry can work toward consensus on the most important issues affecting healthcare innovation, and ultimately, patient care. 

During the summit, one of the programs, entitled “The State and Future of Physician-Industry Collaborations: Spreading Some Sunshine on the Outlook for Innovative Patient Care,” will focus on the Physician Payment Sunshine Act.  This session will be held on June 13, 2012 from Noon – 1:00 p.m. in the Cannon Caucus Room at the House of Representatives, in Washington, D.C.  To attend, email auherek@hlc.org. 

While the Affordable Care Act (ACA) included “sunshine” provisions to ensure transparency and public disclosure, the dialogue on what’s best for patients continues.  This discussion will focus on how to ensure principled collaboration that serves the public interest and furthers the discovery of new cures, treatments, and medical technologies.  This panel will generate discussing surrounding the following questions:   

Is collaboration between physician and industry vital to innovation?

• What is the impact on patients and medical innovation if government goes too far in restricting or discouraging collaboration?
• How do we ensure a balance?

Confirmed Speakers Include:

• William Silverman, DO, Family Practice Physician & former Trustee, American Osteopathic Association
• Phyllis Greenberger, President and CEO, Society for Women's Health Research
• Mary Grealy, President, Healthcare Leadership Council
• Dr. Richard Murray, Vice President of External Medical & Scientific Affairs, Merck & Co.
• Dr. David Charles, Chief Medical Officer, Vanderbilt University Clinical Neurosciences Institute 

 

White House: National Bioeeconomy Blueprint – Encouraging Collaboration

“Economic activity that is fueled by research and innovation in the biological sciences, the “bioeconomy,” is a large and rapidly growing segment of the world economy that provides substantial public benefit.”  As noted in President Obama’s recently published National Bioeconomy Blueprint, “The U.S.bioeconomy is all around us: new drugs and diagnostics for improved human health, higher-yielding food crops, emerging biofuels to reduce dependency on oil, and biobased chemical intermediates, to name just a few.” 

The public benefit gained through bio­logical research can be seen through the eyes of a patient who receives a critical medication that did not exist a decade ago.  The bioeconomy allows Americans to live longer, healthier lives, reduce our dependence on oil, address key environmental challenges, transform manu­facturing processes, and increase the productivity and scope of the agricultural sector while growing new jobs and industries. 

The National Bioeconomy Blueprint describes a number of key elements that will contribute to achiev­ing the potential of the U.S.bioeconomy.  Input from government, industry, and the public has helped to define them. They are: 

• a full spectrum of basic and applied R&D activities performed by academic, government, and private sectors
• public-private partnerships
• a supportive commercialization system for bioinventions
• innovative regulatory policies that reflect government awareness of needs for and impediments to progress
• a skilled and creative workforce
• public support for technological advances
• flexibility to accommodate the evolving needs, discoveries, and challenges 

The Blueprint has two purposes: to lay out strategic objectives that address the key elements to help realize the full potential of the U.S.bioeconomy, and to highlight early achievements toward those objectives.  The Blueprint makes several important recommendations that federal agencies, academia and industry should pay close attention to: 

1. Integrating entrepreneurship and industry involvement into the university research experience will facilitate the path from research to commercialization and help innovative ideas reach the marketplace. 
2. Encouraging federal agencies to pursue “opportunities for effective public-private partner­ships in health to leverage Federal investments and industry investments and expertise.”
3. The need for federal agencies to focus on building new, and augmenting existing, stakeholder collaborations to inform efforts, stream­line processes, and reduce costs and response times, while preserving safety and ensuring substantive benefit to public health.  We recently have seen actions such as this when the Centers for Medicare and Medicaid Services (CMS) decided to postpone data collection under the Physician Payment Sunshine Act and created a collaborative industry/stakeholder workgroup to address the challenges of implementing this section of the Affordable Care Act.  

Background 

Decades of life-sciences research and the development of increasingly powerful tools for obtaining and using biological data have brought us closer personalized medical treatments based on a patient’s own genomic information.  Increasingly, scientists and engineers are looking to augment biological research with approaches from other scientific disciplines for solutions to our most demanding scientific and societal challenges and seeing exciting options that will profoundly affect our future. 

The growth of today’s U.S.bioeconomy is due in large part to the development of three foundational technologies: genetic engineering, DNA sequencing, and automated high-throughput manipulations of biomolecules.  While the potential of these technologies is far from exhausted, a number of impor­tant new technologies and innovative combinations of new and existing technologies are emerging.  Tomorrow’s bioeconomy relies on the expansion of emerging technologies such as synthetic biology (the direct engineering of microbes and plants), proteomics (the large-scale study and manipulation of proteins in an organism), and bioinformatics (computational tools for expanding the use of biological and related data), as well as new technologies as yet unimagined.  There is also a set of emerging trends in recent research that foreshadow major advances in the areas of health, biological-based energy production, agriculture, biomanufacturing, and environmental clean-up. 

In recognition of the potential of the U.S. bioeconomy, in 2010 the Obama Administration included, in its science and technology priorities to inform Federal agency budget submissions, a priority for Federal agen­cies to “support research to establish the foundations for a 21st century bioeconomy.”  Agencies began focusing their efforts accordingly, and have made significant early progress in building a foundation for the future bioeconomy.  In addition, strategic objectives that would help to enable a future vibrant U.S. bioeconomy with potential to deliver major economic and social benefits began to emerge. 

On September 16, 2011, President Obama announced that his Administration would release a National Bioeconomy Blueprint as part of his commitment to supporting scientific discovery and technological breakthroughs to ensure sustainable economic growth, improve the health of the population, and move toward a clean energy future. 

Five Objectives of The National Bioeconomy Blueprint 

The National Bioeconomy Blueprint describes five strategic objectives for a bioeconomy with the potential to generate economic growth and address societal needs.  Although progress is being made in all of these areas, much work remains if the United States is to remain competitive in a changing world.  Summarized below (and described in more detail in the second chapter) are the strategic objectives and the next steps that will help realize the full potential of the U.S. bioeconomy. 

1. Support R&D investments that will provide the foundation for the future U.S. bioeconomy. 

Although many studies show that research provides a healthy return on investment, a major justification for government investments in science and technology is to overcome market failures; these occur when private investors invest less in technology than the socially optimal level because they cannot reap the full benefits of their investment.In this context, scientific discovery is a public good that benefits all. 

The pursuit of a greater understanding of natural systems yields knowledge, ideas, and technologies that the private sector can build on, sparking economic growth by giving rise to new products, services, and jobs.  Coordination of Federal bioeconomy-related research activities can improve the efficiency and effectiveness of those investments and is especially important when budget growth is constrained.  Coordinated strategic programs and targeted investments will accelerate progress in biological research and technology areas, and this in turn will drive discovery for an American bioeconomy.

Moving Forward: Coordinated, integrated R&D efforts will help strategically shape the national bioeconomy R&D agenda. 

Expand and Develop Essential Bioeconomy Technologies – Foundational technologies have made possible unprecedented discoveries in biological research.  Multiagency collaborations for emerging foundational technologies such as synthetic biology, biology-related information technologies, pro­teomics, and others are being fostered in order to grow the bioeconomy. 

Integrate Approaches across Fields – The complexity of modern research questions requires that traditional boundaries between fields of study become permeable and programs concentrate expertise from diverse disciplines around societal challenges where it is needed most.  The Administration will pri­oritize additional multidisciplinary efforts to enable biological research at the boundaries of fields, such as physics, chemistry, engineering, computer sciences, and mathematics, that support the bioeconomy. 

Implement Improved Funding Mechanisms – Creating or modifying funding mechanisms to support creative, high-risk/high-reward research can enable researchers to pursue daring—and potentially groundbreaking—research that may be constrained by typical funding mechanisms or approaches.  Agencies should further explore the use of new or modified funding mechanisms in and across agencies to stimulate the discovery of new bioinventions with potential to grow the bioeconomy. 

2. Facilitate the transition of bioinventions from research lab to market, including an increased focus on translational and regulatory sciences. 

If it is to be successful and thrive, the bioeconomy will be based on a steady flow of new products and services that address American needs.  To ensure this flow, policies must be developed and taxpayer dollars must be used responsibly to foster an ecosystem that supports discovery, innovation, and commercialization.  Moving Forward: A dedicated commitment to translational efforts will accelerate movement of bioinventions out of laboratories and into markets. 

Accelerate Progress to Market – An increased focus on entrepreneurship, translational sciences, regulatory science, and technology transfer can help ensure that ideas with potential for application move beyond the laboratory.  Strategic, coordinated investments in translational and regulatory sciences will accelerate progress in many sectors of the bioeconomy.  To capitalize on the promise of the newly reauthorized Small Business Innovation Research (SBIR) program, agencies should evaluate and update SBIR programs.  Some relevant objectives include reducing application response times, hiring/training program staff to enhance relevant in-house experience, and increasing the use of industry experts as peer reviewers to evaluate industry proposals. 

Enhance Entrepreneurship at Universities – Academic research is traditionally disconnected from its economic implications, making it difficult for innovative ideas to progress beyond the lab.  Integrating entrepreneurship and industry involvement into the university research experience will facilitate the path from research to commercialization and help innovative ideas reach the marketplace.  As an additional benefit, students can be exposed to the broader benefits of academic pursuits, as well as introduced to potential future careers in areas outside of academia.  Innovative programs that enhance entrepreneurial activities at universities are needed to help academic discoveries become commercial realities. 

Utilize Federal Procurement Authority – The purchasing authority of the Federal government offers opportunities to help drive some aspects of the bioeconomy.  By procuring biobased and sustainable versions of products used in agency missions, the Federal government supports markets and promotes innovation, while creating jobs in rural America where many of these businesses are located and bio­products are manufactured.  To drive the creation and growth of new bioeconomy markets, Federal agencies should prioritize procurement of biobased and sustainable products where appropriate and cost-effective. 

3. Develop and reform regulations to reduce barriers, increase the speed and predictability of regulatory processes, and reduce costs while protecting human and environmental health. 

Regulations are essential for protecting human health and the environment and reducing safety and security risks associated with potential misapplications of technology.  When they are not carefully crafted or become outdated, however, they can become barriers to innovation and market expansion and discourage investment.

Moving forward: Improved regulatory processes will help rapidly and safely achieve the promise of the future bioeconomy. 

Improve Regulatory Processes and Regulations – Agencies should improve predictability and reduce uncertainty in their regulatory processes and requirements.  To reduce costs and impediments to invest­ments but without compromising safety and efficiency, attention should be given to application review times, sequential reviews by multiple agencies should be coordinated to allow parallel reviews, and specific guidance should be issued in response to stakeholder needs.  When an emerging technology enters the regulatory process, Federal agencies must have a robust framework that identifies lead agency responsibilities, clarifies supporting agency roles, and delivers timely, specific guidance for applicants. 

Collaborate with Stakeholders – Improved agency regulatory processes rely on productive stakeholder collaborations to identify needs and impediments to progress and investment.  Federal agencies should focus on building new, and augmenting existing, stakeholder collaborations to inform efforts, stream­line processes, and reduce costs and response times, while preserving safety and ensuring substantive benefit to public health. 

4. Update training programs and align academic institution incentives with student training for national workforce needs. 

Many jobs in science and technology-related businesses remain unfilled despite high rates of local unemployment.  Opportunities exist to enhance training efforts at all levels to keep pace with chang­ing career pathways.  At the K-12 and undergraduate levels, the Administration has made significant progress in developing approaches to improve science, technology, engineering, and mathematics (STEM) education, and to increase the number and diversity of STEM students.  For example, in 2009, the President launched the Educate to Innovate campaign to move American students from the middle to the top of international rankings in STEM achievements over the next decade.  Building upon and expanding these efforts, particularly with regard to graduate-level training enhancements, would help to align academic institution incentives with training for future workforce needs.  Also needed is the development of metrics to measure progress over time.  Moving forward: Federal agencies should take steps to ensure that the future bioeconomy has a sustainable and appropriately-trained workforce. 

Employer-Educator Partnerships – Foster increased industry participation in the development of programs and in training students at all levels for the future bioeconomy workforce. 

Reengineer Training Programs – Incentives for academic institutions to enhance entrepreneurship and restructure training programs would better prepare the future bioeconomy workforce, whether individuals are bound for careers in industry or academia.Federal agencies should develop incentives for institutions to adapt training to meet the needs of the 21st-century bioeconomy workforce.Following reengineering of training programs, agencies should consider convening industry stakeholders from various sectors to assess the success of training programs to meet the needs of employers. 

5. Identify and support opportunities for the development of public-private partnerships and precompetitive collaborations—where competitors pool resources, knowledge, and expertise to learn from successes and failures. 

Partnerships enable private industry, government agencies, and academic institutions to pool resources and expertise around an idea, dramatically improving chances for success.  Many companies do not invest in early ideas because they are unlikely to pay off immediately.  This is one place where the government can play a crucial role.  The President has emphasized that the Federal government, universities and companies should work together to invent, deploy, and scale the cutting-edge technologies that will create new jobs, spark new breakthroughs, and reinvigorate America today and in the future.  Moving forward: Federal agencies should provide incentives for public-private partnerships and precompetitive collaborations to benefit the bioeconomy broadly. 

Catalyze Public-Private Partnerships – Great potential exists for partnerships and collaborations where sharing information about successes and failures is anticipated to generate transformative outcomes.  Federal agencies are encouraged to broadly pursue opportunities for effective public-private partner­ships in health, energy, agriculture, and manufacturing to leverage Federal investments and industry investments and expertise. 

Conclusion 

While the Blueprint has some notable goals and recognizes the importance of public-private partnerships as part of a broader strategy to stimulate the economy and realize the full promise of biomedical research, in practice, we have not seen much progress on this part in health care.  For example, the Food and Drug Administration (FDA) still has prohibitive policies for including members on their Advisory Committees who work with industry and the National Institutes of Health (NIH) also have significant restrictions on the involvement of investigators in clinical trials who collaborate and work with industry. 

More importantly, we have Congress passing, and CMS implementing, the Sunshine Act, which paints industry-physician/academia collaboration as inherently unethical and wrong by posting such payments publically online so that media and sensationalist critics can continue their careers bashing doctors and professionals for developing new treatments and educating their peers about them.  

How can the Obama administration be calling for more collaboration, more interaction with industry, more investment and resources to be shared with industry, while at the same time, labeling these relationships as “conflicts” and forcing doctors to disclose their work as if they should be ashamed for saving the lives of millions of patients?  The Obama administration cannot plan to recruit doctors, physicians and scientists to enter into these new collaborations and partnerships and reduce the regulatory burdens while also placing a red target on industry’s back.  

Consequently, a telling quote on page 13 sums up public and congressional frustration with the current model of life sciences R&D: “One issue that government and industry must address is that increased investment in research has not resulted in a concomitant increase in approved drugs.”  In a break from the usual call for industry and academia to align primarily along technical and scientific lines, the Blueprint repeatedly calls for deeper engagement, including academic participation in commercialization.  This document is an example of the multiple and seemingly contradictory messages emanating from various policy centers.

Moving forward, there needs to be a more consistent message throughout the Administration and federal health agencies, which recognizes the important role of industry in navigating through the Bioeconomy, one which does not send mixed messages, and demonize relationships.  Instead, the government must begin to recognize that achieving the objectives of this Blueprint will require significant involvement of industry and private stakeholders who have the patients best interest in mind, and are looking to provide important jobs to hardworking Americans and reinvest their earnings in new technologies and resources.

 

Europe Undermining Innovation by Cutting Drug Prices

A significant part of the health care reform debate and subsequent legislation and implementing regulations is how America can control health care costs.  One of the main purposes of the Patient Protection and Affordable Care Act (ACA) is to address the rising costs and sometimes poor quality of the U.S. health care system. 

Within the legislation and resulting regulations, there have been numerous discussions about how to control costs, while improving quality and patient outcomes.  New payment and reimbursement models, such as bundled payments and accountable care organizations (ACOs) have been proposed, yet it is too soon to know their financial impact.  

During the negotiation phases of the ACA, the life sciences industry promised billions of dollars in the forms of new rebates, discounts and coupons in order to close the Medicare Part D “doughnut hole.”  

More recently, Congress is set to consider the Generic Drug User Fee Act (GDUFA), which would give the Food and Drug Administration (FDA) more money and resources to improve the speed at which they can approve generic drugs.  The implementation of this program could save the federal government billions of dollars since generics cost a fraction of their brand name equivalents. 

Despite all of the promises and negotiations, there has been a constant stream of criticism aimed at the drug industry for charging high prices.  Congress and federal health agencies have targeted drug makers as a main priority to control costs, even though prescription medicines account for only 10 cents out of every dollar spent on healthcare and over 75% of drugs prescribed in the U.S. are already generics.  

In light of all this confusion, a recent lesson in Europe suggests that all of the focus Congress and the media are spending on lowering drug cuts and cutting prices may have a detrimental impact on drug innovation in America. 

Specifically, Pfizer CEO Ian Read explained how “Europe is undermining drug innovation by cutting prices, raising barriers to new medicines and freeloading" off others in Asia and the United States who are more willing to pay.  “European governments are sacrificing the long-term future of science in their countries for the sake of short-term budget cuts.” 

"There is a disconnect in Europe between the marketplace for pharmaceuticals and the desire of European governments to have innovation and research," he said in an interview.  "Europe is not paying its fair share of innovation."  This is extremely disturbing considering the costs to develop new lifesaving treatments can exceed $1 billion and take over seven years to reach the market.   

Tensions between large drug companies and European governments have been rising for several years as administrations across the region face the challenge of curbing the rising costs of healthcare in tough economic times.  Governments are by far the biggest buyers of medicines in Europe, allowing them to dictate prices. 

The article explained that, “The common European practice of cross-referencing to medicine prices in other countries means that exceptional price cuts in Spain or Greece will trigger knock-on cuts elsewhere.” 

Read hit out at governments who have slashed drug prices and racked up close to $20 billion in unpaid bills for medicines, largely in southern Europe, saying their increasing reluctance to pay up for innovative therapies would come back to haunt them.

"The pharmaceutical industry requires a vibrant marketplace.  It's a high-risk business ... and a high-risk business needs the potential for high returns.  So in the end, European leaders are sacrificing the long term for the short term," Read said. 

GlaxoSmithKline Plc Chief Executive Andrew Witty said last month he now ranked Europe behind the United States and Japan as a market where he would want to launch new products.  Bayer AG CEO Marijn Dekkers has also expressed concern about Europe's direction, noting in a recent results presentation that the money earned from today's drugs was needed to pay for developing the medicines of tomorrow. 

Pfizer's Read singled out Germany for particular criticism, pointing to Berlin's recent decisions to extend drug price freezes from 2010, which were initially designed as an emergency measure, and to use a basket of countries including Poland and Greece as a benchmark for how much it will pay for drugs.  Since Germany is one of Europe's wealthiest countries, Read questioned whether referencing its prices to Greek or Polish levels would offer drugmakers a fair return. 

"What is the fundamental message there?  They are saying ... investment in innovation is at a level that Greek prices can support.  That's not a recipe to create an innovative industry that can compete on the world stage,” Read said.  Instead, he wants European government to take a longer-term view and engaging on the issue of who should pay for the research and development costs of cutting-edge medicines. 

Conclusion 

Given the difficulty, drug companies are facing in Europe regarding government reimbursement, Congress and other health officials in charge of policymaking for reimbursement and other payment related decisions should look to these events as an example.  If the Centers for Medicare and Medicaid Services (CMS) begins cutting reimbursement rates for innovative new drugs or the ACA, through the Independent Payment Advisory Board (IPAB) or the Patient Centered Outcomes Research Institute (PCORI), companies may begin to send even more jobs and products overseas. 

The high-risks of developing drugs, in the particularly rigorous regulatory environment set by FDA, warrants high-returns for companies.  Without reinvestment, companies will not be able to find cures or the next greatest breakthroughs and patients will suffer.