Another tool helping developers navigate the difficult road to approval of drugs for rare diseases

By: Jonathan Goldsmith, M.D., F.A.C.P.

If you personally know 100 people living in the U.S., chances are that almost 10 will suffer from some form of a rare disease. If that makes it sound like rare diseases are not actually very rare in this country, that’s because there are 7,000 different rare diseases, 80% of which are caused by faulty genes. A rare disease is defined as a condition that affects fewer than 200,000 people living in the U.S., a country with almost 320 million people. When we do the math, it turns out there are roughly 30 million Americans who suffer from a rare disease. And sadly, about 50% are children.

Dr. Jonathan GoldsmithWith the vast majority of rare diseases still without FDA-approved treatments, we have recently released a new resource for drug developers — a draft guidance document — designed to help them navigate the difficult and unique challenges of developing and bringing to market new FDA-approved drugs to treat rare diseases.

When it comes to finding ways to test new treatments for rare diseases, we often cannot rely on the same methods that we use for testing treatments for more common, well-known diseases, such as diabetes or high blood pressure. Here’s why: In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease, the lack of medical understanding of the disorder (because relatively few people suffer from it), and the lack of well-defined study results (endpoints) that can demonstrate that a potential treatment for a rare disease is safe and effective.

The new draft guidance is intended to help drug developers create more accurate and timely drug development programs by encouraging

  • a focus on understanding a disease’s “natural history,”
  • creation of study designs with clinically meaningful endpoints,
  • development of evidence needed to establish safety and effectiveness,
  • and the establishment of drug manufacturing specifications to ensure quality.

It is also important to note that FDA regulations provide flexibility in applying regulatory standards because of the many types and intended uses of drugs. Such flexibility is particularly important for treatments for life-threatening and severely-debilitating illnesses and rare diseases.

Our guidance document will help us build on the gains we’ve made in helping patients with rare diseases. Since the passage of the Orphan Drug Act in 1983, the number of new requests for orphan designation has continued to rise. In 2014 we saw 469 requests, the highest number of new requests in one year. Also in 2014, an unprecedented 41 percent of all novel new drugs (17 of 41) approved by FDA’s Center for Drug Evaluation and Research were for the treatment of rare diseases.

Our guidance document is intended to encourage drug developers to think early on in the process about all aspects of their program — and encourages careful planning which includes a foundation in strong science. Drug developers for rare diseases are often pioneers. Pioneers need maps and tools to guide them. We see this guidance as another important resource to help support their efforts.

FDA is committed to working with all drug developers and stakeholders to establish successful drug development programs that include regulatory flexibility, creative approaches and a scientifically sound basis.

Jonathan Goldsmith, M.D., F.A.C.P., is FDA’s Associate Director, Rare Diseases Program, Center for Drug Evaluation and Research

Rare Diseases at FDA: A Successful Year for Orphan Products

By: Gayatri R. Rao, M.D., J.D.

2014 was a strong year for rare disease product development at FDA. It was also a year of significant firsts.

Dr. Gayatri RaoIn recognition of Rare Disease Day, February 28th, we want to reflect on the progress we have made thus far as we renew our commitment to rare disease patients. A rare disease is generally defined as a disease which affects fewer than 200,000 Americans a year. At FDA, the commitment to increase access to diagnostics and treatments to change the day-to-day reality of those living with rare diseases began over 30 years ago with the passage of the Orphan Drug Act.That commitment has steadily increased since then.

In 2014, we received our highest number to date of new requests for orphan drug designation. We received over 440 requests while just 7 years ago, we received less than half of that. We designated and approved more orphan drugs in 2014 than we had in previous years – nearly 300 drugs were designated and 48 were approved, including both novel and repurposed drugs. In 2014, 41% of all novel new drugs approved by the Center for Drug Evaluation and Research were for the treatment of rare diseases. Many of these orphan drug approvals were new and innovative, including Sylvant, to treat Castleman’s disease, which results in excessive lymph node growth, and Impavido, to treat forms of the tropical disease, leishmaniasis.

2014 was also a year of firsts for rare disease product development:

There were firsts in device development. For example, the Center for Biologics Evaluation and Research approved its first device through the Humanitarian Device Exemption (HDE) pathway. This device, CliniMACS CD34 Reagent System, helps to mitigate potentially serious immune reactions associated with stem cell transplantation in patients with acute myeloid leukemia.

FDA produced in 2014 its first agency-wide blueprint to accelerate the development of therapies for pediatric rare diseases – a report and strategic plan outlining how to address issues for developing products for this population.

2014 saw the issuance of the first rare pediatric disease priority review voucher for the treatment of mucopolysaccharidosis type IVA (Morquio A syndrome), a rare lysosomal storage disease which affects about 1000 patients in the United States and can lead to debilitating and life-threatening abnormalities of bones, joints and the heart.

In recognition of Rare Disease Day 2015, the international rare disease community is coming together to pay tribute to the millions of individuals impacted by rare diseases all over the world. Through the solidarity and commitment of many stakeholders – patients and families, healthcare professionals, researchers, companies, and policy makers – the awareness of the daily challenges that are unique to each rare disease and the efforts to create solutions has risen exponentially in the past several decades. As members of the rare disease community, we are proud of our collective accomplishments but remain acutely aware of how much more there is still to be done. Given how 2015 is already shaping up, we expect that by working together, we will continue to make great strides in developing much needed products for the millions of patients living with rare diseases.

Gayatri R. Rao, M.D., J.D., is FDA’s Director for The Office of Orphan Products Development

FDA Commemorates 30th Anniversary of the Orphan Drug Act

By: Gayatri R. Rao, M.D., J.D.

When President Reagan signed the Orphan Drug Act 30 years ago, he enacted a critically important piece of health care legislation. The passage of this Act on January 4, 1983, was monumental because it created—for the first time—incentives to develop desperately needed medical products for Americans suffering with rare diseases. Until that point, development of such products was very limited. For instance, in the decade leading up to the passage of the Orphan Drug Act, only 10 industry-supported products for rare diseases were brought to market.

Gayatri Rao 0215The Office of Orphan Products Development (OOPD) was formed at FDA more than 30 years ago, prior to the passage of the Orphan Drug Act, because FDA recognized that rare diseases, when taken together, posed a significant national public health issue. Once the Orphan Drug Act was passed, OOPD became responsible for administering the incentive programs created to spur the development of medical products for rare diseases, namely the Orphan Drug Designation Program and the Orphan Products Grants Program. These products include drugs, biologics, medical devices, and medical foods for the treatment of rare diseases.

As FDA commemorates the passage of this important legislation, we look back over the last 30 years with pride. Since its passage, over 2700 products in development have been designated as orphan drugs through the Orphan Drug Designation Program and over $290 million has been awarded to clinical studies through the Orphan Products Grants Program.  These programs, along with the critical, collective efforts of the Center for Drug Evaluation and Research’s (CDER) Rare Diseases Program, and those of many individuals across FDA, have helped to bring over 400 orphan products for rare diseases to the market.

We also commemorate the more than 30 years of dedicated service from every member of the rare disease community:

  • the patient advocates, who spurred national awareness about the challenges that people with rare diseases face and who continue to support families, educate the community, and drive research into their diseases;
  • the legislators who heard the voices of rare disease advocates and worked to champion the passage of the Orphan Drug Act;
  • the research community, which continues to leverage resources and foster collaborations among academia and industry stakeholders;
  • the clinicians, who support the medical needs of families with rare diseases and work to advocate on behalf of the community;
  • and industry, including pharmaceutical and biotech companies, angel investors, and venture capitalists who, in the spirit of the Orphan Drug Act, have come together to develop products for rare diseases.

Our many successes give us a reason to celebrate 30 years of hard work to provide diagnostic or treatment options to those with rare diseases. But we are keenly aware that there is still a challenging road ahead. We at FDA remain firmly committed to working with the rare disease community to tackle those challenges and to find new diagnostic tools and treatments for the millions of patients with rare diseases.

Gayatri R. Rao, M.D., J.D., is Director for The Office of Orphan Products Development