It is hoped that new laws and partnership-building will increase the number of drugs approved for the over 7,000 diseases given orphan status. [© Dalibor Zivotic - Fotolia.com]
On signing the Orphan Drug Act into law on January 4, 1983, President Ronald Reagan lamented, “I only wish with the stroke of this pen I could also decree that the pain and heartache of people who suffer from these diseases would cease.” More than a quarter-century later, the prospect of Washington relieving that pain and heartache any time soon remains elusive.
The orphan drug law served its initial purpose of facilitating R&D, and ultimately treatments, focused on rare diseases. However, as drug developers and patient advocates correctly note, much more remains to be done. Some 25 million Americans have one of the more than 7,000 diseases given orphan status. Only 2,400 drugs have orphan designations, though, and 367 have been approved, Timothy R. Coté, M.D., who until recently headed FDA’s Office of Orphan Products Development, told GEN.
There are some encouraging signs for rare disease research, from proposed new laws to ongoing efforts by NIH and FDA to unite researchers, patient advocates, and companies focused on developing therapies.
“It’s just amazing how things are coming together for many of the rare diseases,” Stephen C. Groft, Pharm D., director of NIH’s Office of Rare Diseases, said to GEN. “Before there really was not a lot of hope, and I think now we’re seeing with this coordinated effort that you can identify potential compounds. You can move compounds forward, and they can be made available to patients and their practitioners. But it does require a lot of coordination.”
On the legislative front, in March Senator Robert P. Casey Jr. (D-PA) introduced the Creating Hope Act (Senate Bill 606). The Creating Hope Act has five co-sponsors—three democrats and two republicans. The measure would enable drug developers who submit an orphan drug for review to receive a “priority review voucher.” The bill would also allow for vouchers to be sold or transferred more than once.
As of May 31, the only action by the Senate on the bill was a referral to the Committee on Health, Education, Labor, and Pensions. A Casey spokesman did not return a message from GEN about the prospects for action on the bill.
“We are hoping to have it introduced in the House of Representatives in the next two months, but unfortunately support is not airtight at this point, so I can’t give assurance as to a specific date,” Nancy Goodman, founder and executive director of Kids v Cancer, a patient advocacy group that has endorsed the Creating Hope Act, told GEN.
As with the Senate measure, Goodman said, supporters are seeking a bipartisan group of House sponsors. So far two Republicans have emerged.
The Creating Hope Act reflects greater activity by advocates, as does the re-establishment of the dormant Congressional Rare Disease Caucus. Twenty U.S. representatives are members of the coalition, which is co-chaired by a republican and a democrat.
“It’s really just getting started now, and we’re encouraging our members to ask their Congressional representatives to join,” Mary Dunkle, a spokeswoman for the National Organization for Rare Disorders (NORD), told GEN. NORD is a nonprofit umbrella group for organizations that represent patients with rare diseases.
NORD also joined with its European counterpart EURORDIS-Rare Diseases Europe to encourage FDA and EMA “to look at their interface and policies and procedures and see whether there may be any unnecessary duplication or ways to accelerate the development of treatments.”
Stateside, Dunkle said, NORD and other advocates are working to build support for renewing three bills whose authorizations will expire next year:
- Best Pharmaceuticals for Children Act (2002): Grants six months of additional marketing exclusivity and patent protection to drug companies that agree in return to provide FDA with data from children on dosaging, labeling, and pharmacokinetics with respect to pediatric diseases. But incentives, first offered in the Food and Drug Administration Modernization Act (1997), do not apply to biologics.
- Pediatric Research Equity Act (2003, reauthorized 2007): Requires drug developers to test a new drug in a pediatric population if the agency determines the product is likely to be used in a substantial number of children or provide meaningful benefits for children over existing treatments.
- Prescription Drug User Fee Act (1992, reauthorized 1997): Authorizes FDA to collect user fees from drug companies for drug products.
Perhaps, however, the brightest hope for aiding orphan drug development rests with the budget for the coming fiscal year, which starts October 1. The $3.8 trillion budget proposed by President Obama includes the creation within NIH of a new institute designed to promote translational medicine. The National Center for Advancing Translational Sciences (NCATS) would concentrate in one place $700 million allocated for existing NIH units scattered across the agency, including the Office of Rare Diseases Research.
Christopher P. Austin, M.D., senior advisor to the director for translational research at NIH, described NCATS’ strategy for orphan diseases as orthogonal. “The center will look at the similarities in 1000s of rare diseases and look at therapeutic approaches that may affect multiple of them simultaneously, instead of going down the traditional route, which is to pick a disease, pick an approach, and then push very hard on that one very narrow approach.”
NCATS would oversee the Therapeutics for Rare and Neglected Diseases (TRND) program, a $24 million NIH initiative launched in 2009 to stimulate collaborations with academic scientists. Dr. Austin said TRND currently has five pilot projects, with plans to ramp up to 10 projects at various stages of preclinical research.
NIH Director Francis S. Collins, M.D., Ph.D., said he hoped to open NCATS on October 1. That assumes lawmakers will have approved a budget by then, a risky supposition at best given that Congress is already sharply split on various issues.
Until the budget became a major issue, Washington had been ramping up spending for rare diseases. In addition to launching TRND, NIH expanded its Rare Diseases Clinical Research Network in 2009. It spent just over $117 million over five years to fund 19 research consortia and a Data Management Coordinating Center, with the goal of studying the natural history, epidemiology, diagnosis, and treatment of more than 95 rare diseases.
NIH and FDA Initiatives
NIH and FDA also came together in asking the Institute of Medicine of the National Academies to study the opportunities and obstacles for developing treatments for orphan diseases. The resulting report “Rare Diseases and Orphan Products: Accelerating Research and Development,” issued last year, called for an “integrated national strategy to accelerate research and product development for rare diseases” as well as several specific action recommendations:
- NIH should develop a comprehensive action plan for rare disease research that would cover research program planning, grant review, training, and coordination of all phases of research.
- NIH should increase its capacity and flexibility to support all phases of clinical research related to rare diseases, including clinical trials of new and repurposed therapeutic agents.
- FDA should expand its Critical Path Initiative to define criteria for the evaluation of surrogate endpoints for use in trials of products for rare conditions.
- FDA’s Center for Drug Evaluation and Research (CDER) should evaluate the extent to which studies submitted in support of orphan drugs are consistent with advances in the science of small clinical trials and associated analytic methods.
“It’s fair to say that this whole effort in rare diseases and orphan diseases is dramatically under-resourced, underfunded, and uncoordinated,” Dr. Austin said. “To have the National Academies say that is the case was very helpful, frankly. In an environment of tough competition for budgets, it helps to have the National Academy come out and say, ‘We think this is a very important problem, and here’s what you ought to do to help solve it.’”
Dr. Groft cautioned, however, that the report’s findings are unlikely to be carried out quickly: “Many of these recommendations are just not things you can accomplish within six months or nine months, but they do take years both of planning and then of implementation.”
NIH and FDA are in their third year of co-sponsoring a course in the design of small clinical trials. The joint activity has proven valuable, Dr. Groft said, by shedding light on the sheer complexity of studying rare diseases, which requires researchers from NIH’s numerous institutes to develop therapies by working together and building partnerships with patient advocates and industry.
FDA early last year created a new associate director for rare diseases position within CDER’s Office of New Drugs that would be “a focal point for the rare disease drug development community” by helping drug and biologic developers and others with a stake in creating orphan drugs navigate the agency’s complex regulatory requirements.”
Also last year, FDA launched the Rare Disease Repurposing Database, listing products that have received orphan status designation and are already market-approved for the treatment of some other diseases.
“It’s going slowly, but it’s going forward,” Dr. Coté told GEN. He said FDA has spoken to “a number of” prospective sponsors interested in supporting the repurposing of drugs for orphan diseases,” but couldn’t disclose details.
The emergence of those sponsors, along with new laws, continued partnership-building, increased advocacy, and NIH-FDA initiatives are all likely to help people with orphan diseases find the treatments they need. But like the FDA database, while progress may be indeed going forward, it’s also going slowly.