Building a 21st Century FDA: Getting new treatments out of the pipeline and into the hands of patients requires more than just good research

By Gillian Parrish, Manager, Alliance Development and Communications

Every day, hundreds of thousands of lives are indefinitely on hold – patients waiting for effective treatment options to become available, families waiting for their loved ones to start having a better quality of life, the list goes on. At a standstill – and that’s if they’re lucky – because research that promises to curb their disease has yet to translate into new drugs or devices they can utilize.

Often, when a new molecular entity or biomarker is discovered that has promising implications for disease treatment, it gets waylaid for years in a needless web of outdated regulatory processes that are under-resourced and ill-equipped for modern scientific review. According to a report by Nature Reviews Drug Discovery, the number of new molecular entities approved by the FDA has dropped steeply in the last 15 years – from 53 in 1996 to 19 in 2009, over a period when the budget for National Institutes of Health (NIH) nearly doubled. And most patients living with serious illness can’t wait the 10-15 years it takes to move a new discovery through the current development, testing, and regulatory review process.

While increasing funding for NIH research is a critical step in finding cures, it’s only part of the equation. The remaining part depends on improving the regulatory process, building capacity—both financial and scientific—at the Food and Drug Administration (FDA) so it can carry the baton of innovation from the research community across the regulatory “finish line” to patients. One vehicle for speeding review and access is the Prescription Drug User Fee Act (PDUFA), which is due for its fifth Congressional reauthorization in 2012.

The advocacy community’s role in reauthorizing an effective PDUFA was the focus of a panel hosted by BIO and PhRMA last week. Panelists Marc Boutin (National Health Council), Marcie Bough (American Pharmacists Association) and Jeff Allen (Friends of Cancer Research) called upon advocates to step up and be disruptive, working collaboratively with each other and with industry to speed product reviews and ensure the right balance between safety and access. Margaret Anderson (FasterCures) who moderated the discussion summarized the key themes at the end of the briefing:

• Making sure the patient perspective is heard throughout the reauthorization process
• Applauding FDA’s efforts to be more transparent, and taking them up on their willingness to have a two-way dialogue
• Working together across sectors and diseases to find and leverage commonalities like:
  - Improving REMS – Creating a standard Risk Evaluation and Mitigation Strategies (REMS) template, involving patients in the evaluation process, and establishing clearer metrics
  - Incorporating Regulatory Science – Though user fees aren’t typically applied to scientific programs, reviewing drugs is a complex process that requires a complex way of thinking, and process science should be incorporated into PDUFA to increase efficiencies
  - Advancing Public Education – Helping patients and consumers understand what FDA can do for them, and mobilizing them to act
  - Balancing Fees and Appropriations – The appropriated base of human drug review has not kept pace with FDA’s workload (currently ~65% is paid for by user fees); a consistent, multi-year funding approach is necessary to operate a modern-scientifically based regulatory program

“Partnering with Patients” at the Biotech Industry Organization Convention

by Kristin Schneeman, Program Director, FasterCures

All I can say is, I wish I’d read Maureen Martino’s FierceBiotech blog before I left for Chicago.

A week and a half ago I was gearing up to moderate a panel discussion at the Biotechnology Industry Organization’s annual convention in Chicago about venture philanthropy and the impact it’s having in accelerating the development of new treatments for patients. We’ve chaired panels similar to this one at BIO in the past, highlighting the financial resources patient organizations can bring to the table and the partnerships they’re increasingly forming with companies to develop products. This year we decided to focus in a little more on the non-financial assets these organizations also bring -- the “patient capital” in the form of tissue banks, medical data, and participation in clinical trials – as well as their ability to serve as “systems integrators” bringing all of the stakeholders together and smoothing over the information and funding gaps in the research process.

We assembled a phenomenal panel - passionate patient advocates, but also serious and successful R&D professionals -

many of whom had come from industry, started companies, and consulted with companies. They included:

• Howard Fillit, Executive Director of the Alzheimer’s Drug Discovery Foundation (ADDF);
• Dick Insel, Vice President for Research at the Juvenile Diabetes Research Foundation (JDRF);
• James O’Leary, Chief Innovation Officer at Genetic Alliance (GA);
• Louise Perkins, Chief Scientific Officer at the Multiple Myeloma Research Foundation (MMRF); and
• Steve Perrin, Chief Executive Officer and Chief Scientific Officer at the ALS Therapy Development Institute (ALS TDI).

Their organizations have invested more than a billion dollars in medical research, have global reach, have supported hundreds of drug discovery programs and scores of clinical trials, and have played a critical role in development of products that are helping patients today.

Among the many impressive nuggets I jotted down during the session:

• MMRF has demonstrated its ability to activate clinical trials 30-40% faster than the industry standard, through its powerful consortium of 13 leading academic research institutions.
• JDRF is pursuing more than 20 development efforts in partnership with companies -- many of which have been picked up by large industry players – including novel agreements with Johnson & Johnson and Novartis to help those companies fill their product pipelines.
• ADDF has been instrumental in the creation of several startup companies that have gone on to leverage enormous amounts of follow-on investment.
• GA is providing resources to help patient groups in rare genetic diseases marshall the patient assets they need to help them engage companies in developing treatments for those diseases.
• ALS TDI has created a new model, a “nonprofit biotech company,” that is shaving millions of dollars off the development process and de-risking industry investment “by keeping patients in mind from the very start.”
  
  

• • At the end of the session, I offered a question for further reflection and discussion: What are the implications of putting the patient (intermediated by organizations like these) at the center of the research and development process – not as research subjects or consumers, but as partners and decisionmakers?

After I left Chicago I came across a blog posted by FierceBiotech’s Maureen Martino from BIO earlier in the week. In it she recounts her chance conversation with three breast cancer survivors in an airport shuttle. She asked them what they would say if they could talk to the companies developing breast cancer treatments: “A whole lot, as it turns out.”

Among their frustrations was the lack of true communication among patients, their physicians, and particularly the companies developing drugs to help them. “They should pay us to come talk to them,” commented one. She may have said it half in jest, but I suggest we take that idea seriously. And invite the FDA to listen in.

Kudos to Maureen Martino for trying to present a “human face [to] the drug industry.” We’ve been trying to do the same thing for a number of years by supporting the work of innovators like our BIO panelists, who are the trusted intermediaries for meaningful participation by patients in the research process. As a participant at a recent FasterCures meeting has said, “Patients are the only unique resource in the entire continuum … they can create the ultimate bargaining unit.” Where’s Norma Rae when you need her?

Leveraging Existing Resources and Crown Jewels

By Margaret Anderson, Executive Director, FasterCures

On my way to participate in a meeting of the NIH Scientific Management and Review Board (SMRB)—formed in 2006 to advise NIH on the use of organizational authorities given to it by the NIH Reform Act—I walked through the lobby of the Clinical Center. It’s an incredible facility, the largest dedicated research hospital in the country, housing some of the nation’s best imaging equipment and clinical research expertise. In the lobby area of the Clinical Center, I saw clusters of people, many of them families and friends of patients, their faces reflecting two things: fear and hope.

Our nation’s research crown jewel ignites hope – it features some of the greatest scientific minds using the most advanced medical technologies. And yet, when we checked on its utilization a year and a half ago as part of our Task Force on NIH’s Intramural Research Program, it was far from fully utilized. Recognizing this untapped potential, the SMRB invited experts (such as Robert Califf, Art Levine, Bill Crowley and Samuel Silverstein, among others) to advise them on opportunities and challenges for expanding the use of the Clinical Center to external researchers.

They agreed that while intellectual property and conflict of interest issues would need to be addressed and operationalized, there was no major impediment to outside investigators using the clinical center, and noted that many academics and nonprofit disease research foundations were, in fact, ready and eager to start utilizing the Center’s many training and research resources immediately.

Last year, FasterCures issued a white paper developed by our Task Force on NIH’s Intramural Research Program that recommended an enhanced and expanded role for and use of the NIH Clinical Center so we were particularly pleased the SMRB decided to take this issue on. And we were not alone. In advance of the SMRB meeting, we circulated a letter within the patient advocacy community to gauge support for the premise that the Clinical Center be made available to the external research community. Within days, 86 other organizations signed-on. In the letter to Director Collins and the SMRB, the patient community recommends the NIH:

• Create streamlined mechanisms by which external researchers can more fully use the Clinical Center for projects in collaboration with the IRP (for example, giving the Clinical Center and/or Institutes the flexibility and authority to negotiate broader collaborative agreements or public-private partnerships, taking into consideration ethics rules and intellectual property rights).
• Explore the possibility of the Clinical Center controlling a pool of funds to make use of the facility feasible for investigators who otherwise could not afford it (for example, through a program similar to the existing Bench-to-Bedside Awards).

At the end of the meeting, Director Collins charged the SMRB with a new and potentially path-breaking task, to advise him on how NIH could create what he referred to as a more “integrated therapeutics program” that pulls existing NIH resources—like TRND, RAID, the CTSAs, and the newly authorized Cures Acceleration Network (CAN)—into an efficient pipeline for therapeutic development. “It’s not about shifting emphasis away from basic research, which will be more important now than ever,” Collins assured Board members. Instead, he said it’s about reorganizing NIH to better support the translation of those discoveries into medical solutions patients can use.