Salvatore La Rosa, Ph.D.
Annette Bakker, Ph.D.
Marco Nievo, Ph.D.
Developers are coming up with alternative ways to research and develop therapeutics that don’t involve buying Boardwalk.
Until very recently, it was easy to think of drug discovery and development as a competition, a game something like Monopoly, the Hasbro classic.
In Monopoly, the top hat, Scottie dog, and flat-iron raced to snap up Park Place and Boardwalk. In pharma, Roche, Novartis, and Lilly vied for market share in oncologics or antihypertensives. Monopoly had deeds for properties; pharma had patents for drugs. Monopoly players built houses and hotels; pharma companies discovered candidates, ran clinical trials, launched products, and built franchises on their intellectual property. Pharma played by rules made by FDA, EMEA, Centers for Medicare & Medicaid Services, private health insurers, the FTC, SEC, and Sarbanes-Oxley; families played Monopoly by the rules that came in the box. Monopoly players tried to amass all of the cash in the bank and drive the other players into bankruptcy; pharma marketers competed for market dominance. The winner won at the loser’s expense.
Time for a New Game
This pharmaceutical game is no longer sustainable, and a widening community of drug developers is looking for alternatives. (So, for that matter, are some board game players. Consider, for example, the popularity of the award-winning Pandemic, in which teams from the Centers for Disease Control and Prevention band together to stop the spread of deadly diseases—everybody wins, or everybody loses.) In these new games, new players are using new models of cooperation, in which everyone can win if they work together.
In drug development, we are finally recognizing that these new players—most notably the patients, the ultimate customers of the drug discovery chain—are critical to developing and commercializing new drug candidates. Patient-reported outcome studies are increasingly vital to any medicine evaluation and can make the difference between approval and nonapproval, especially in disease areas where hard clinical facts may not tell the entire story.
In the process, foundations and other collaborators have become vital partners for for-profit drug companies. Medical foundations bring to the table scientific expertise, an understanding of the patients, a valuable historical perspective, and essential connections to academia, government, and industry. Today, more medical foundations have begun to take an active role in finding gaps in research and directing their considerable funding power to recruit researchers to fill those gaps.
This support is critical to developing treatments for rare diseases. Rare-disease economics have made pharmaceutical companies gun shy about investing in treatments for conditions that affect only a few tens of thousands of people, even if the FDA has been extremely helpful in this process by implementing reforms under the Orphan Drug Act of 1983.1 Yes, policy changes have made it easier—and less expensive—to win approval for orphan drugs. But R&D costs are still high—sometimes too high to reasonably recoup from a small patient population. Despite these strictures, the Pharmaceutical Research and Manufacturers’ Association 2013 report on “Medicines in Development: Rare Diseases” lists more than 450 compounds under active development, including 85 aimed at genetic disorders.2
In this environment, where collaboration spreads the risk and amplifies the effort, the foundation partner has to do more of the early heavy lifting. Good data from one animal model and a Phase I safety trial are not a strong enough foundation for a commercial partnership. A good Phase IIb package is today’s minimum ticket for admission to serious alliance talks.
Foundation Leadership
Vigorous foundation leadership can make cooperation among the various players not only possible, but mandatory for entry into the game. As Pfizer’s president of worldwide R&D noted recently, foundation partners help pharma companies “de-risk early stages of research, prioritize endpoints, support clinical trial recruitment, and provide insight into disease.”
Over the past six years or so, many rare-disease medical foundations have stepped up their scientific activism, and government funders have started to embrace the cooperative model. We may be witnessing the end of “just funding research” and the start of a new era of broad collaboration.
Cooperative initiatives include the federally funded Patient-Centered Outcomes Research Institute (PCORI, chartered in 2010); new ecosystems of research cooperation, such as initiatives like SU2C (the American Association for Cancer Research’s Stand up to Cancer), Synodos (the Children’s Tumor Foundation dream team model named for the Greek for “on the same path”)3 and NIH’s collaborative SPORE grants; a recently announced public-private venture between pharma and nonprofits to collaborate with the NIH and FDA to pool information to find candidates for treating Alzheimer’s disease, lupus, rheumatoid arthritis, and diabetes;4 a growing number of research “dream teams” taking on specific cancers; real-time data-sharing infrastructures, like Sage Bionetworks’, that create information communities; and a growing number of nonprofit medical foundations moving full-tilt into drug development.
Basic Tools: Programs and Infrastructure
The activist foundations have two key tools: programs and infrastructure. “Programs” include grants, of course, but foundations are managing their giving in a new way. Where they were once miniature National Institutes of Health, foundations are now using their experience and expertise to direct research more vigorously (more in tune, perhaps, with the model of the Defense Advanced Research Projects Administration, DARPA, which gives project managers significant discretion to define and pursue particular research goals).
Here are just a couple of examples of foundations taking the reins.
Start with 2008, when the Huntington’s disease community, the Hereditary Disease Foundation, and the Huntington’s Disease Society of America succeeded in a decade-long effort to get the U.S. Food and Drug Administration to amend the label of tetrabenazine (Xenazine) to include treatment of the chorea associated with Huntington’s disease.5,6
The Alzheimer Drug Discovery Foundation’s ACCESS program strongly supports collaborations between academic groups and contract research organizations. The Leukemia & Lymphoma Society worked with Celgene in its first “Targets, Leads & Candidates Program” to build a new venture partnership. The Children’s Tumor Foundation has adopted a business model aimed at accelerating the path from basic discovery to clinical benefit, by strategically investing in building bridges between all stakeholders.
These efforts can clearly show results. In 2012, the Cystic Fibrosis Foundation (CFF) and Vertex Pharmaceuticals won approval of Kalydeco (ivacaftor), the groundbreaking “first drug…that targets the underlying cause of CF” by reversing the protein malformations produced by specific, diagnosable mutations in the CF gene. The treatment was discovered, developed, and approved with “significant scientific, clinical, and financial support throughout … including a $75 million investment,” from CFF.7
Support Platforms
Foundations can make this kind of targeted financial support and scientific guidance even more effective by giving researchers badly needed research support tools. The beauty of these infrastructure systems is that each component platform comes as a standalone piece and can be built at any time. Each piece fills a gap and leverages the investment; in combination, the effect can be exponential.
These research support tools include:
- Patient registries, to increase the speed and lower the cost of clinical trial recruitment.
- Patient tissue repositories available to qualified researchers with specific questions about the disorder’s biology.
- A safe information ecosystem in which research teams can freely share data.
- “On demand” services and tools, including compound scouting, data visualization, project management, medicinal chemistry resources, intellectual property intelligence, model materials transfer agreements, market analyses, and help with contract negotiation.
- Regular, high-quality worldwide conferences that bring together researchers for scientific exchange and other stakeholders for community-building.
- Networks of clinics specializing in the disorder, able to provide expert treatment and support to patients, and accurate, up-to-date information to families.
Rules of the New Game
So all a modern major medical foundation needs to do is forge strategic alliances, enlist, and empower top scientists, identify and fund top research, build the necessary infrastructure, plot out a research strategy, address specific tasks, acquire industrial knowledge, and deal with every aspect of the disease.
That’s the new game.
We believe this is just the beginning of a new era. The basic rule for an alternative research game is simple, though: share and collaborate.
Achieving big results requires big investments. Realizing great discoveries demands great coalitions. Tackling a complex disease alone is like playing a symphony on a kazoo: It will never come out right.
Yes, maybe Monopoly once was the only game in town. Today, though, there are better ways to play. Everyone who can make a meaningful contribution deserves a place at the board. And redesigning the research landscape is the prize.
Salvatore La Rosa, Ph.D. ([email protected]), is director of research and development, and Annette Bakker, Ph.D., is the president and CSO of the Children’s Tumor Foundation (CTF). Marco Nievo, Ph.D., is a European patent attorney in the pharmaceutical industry who collaborates with the CTF in implementing IP policies.
Works Cited:
1 21CFR36: Orphan Drugs. Electronic Code of Federal Regulations. [Online] [Cited: March 26, 2014.] http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&SID=51cf70689d51f0ea4147c0a8ac649321&rgn=div5&view=text&node=21:5.0.1.1.6&idno=21.
2 PhRMA, Pharmaceutical Research and Manufacturers of America. Medicines in Development: Rare Diseases–a report on orphan drugs in the pipeline. Washington, DC : PhRMA, Pharmaceutical Research and Manufacturers of America, 2013.
3 Children's Tumor Foundation. Synodos: A turning point for NF2. Children's Tumor Foundation. [Online] [Cited: March 26, 2014.] http://www.ctf.org/Research/Synodos.html.
4 Reardon, Sara. Pharma firms join NIH on drug development. Nature. February 4, 2014.
5 Rubin, Rita. Doctors, families fought for approval of Huntington's drug. USA Today. 2008, 28 October 2008.
6 U.S. Food and Drug Administration. Xenazine. Drugs@FDA. [Online] [Cited: March 26, 2014.] http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails.
7 Cystic Fibrosis Foundation. Kalydeco. Cystic Fibrosis Foundation. [Online] [Cited: March 26, 2014.] http://www.cff.org/treatments/therapies/kalydeco/.
