Rare Diseases in Children Pose Unique Challenges

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

Rare diseases – those that affect fewer than 200,000 people in the United States but collectively affect 30 million Americans – are often chronic, progressive, debilitating, and life-threatening. Because most are genetic in origin, they disproportionately affect children. The agency is strongly committed to advancing safe and effective therapies for these young patients.

Gayatri R. Rao, M.D., J.D., is Director of FDA's Office of Orphan Products DevelopmentIn recognition of International Rare Disease Day on February 28, 2014, we are focusing on pediatric rare diseases.

While developing products for any rare disease poses challenges, in part because of the small patient populations, developing products for children raises unique considerations.  Historically, pediatric care has involved the use of off-label therapies that are unstudied or under-studied in children. For example, pediatric drug dosing often involved adjusting adult doses based on a child’s decreased weight, without considering potential age-based differences in drug metabolism and toxicities. Similarly, many medical devices used in children have been adapted – in homes, clinics, and operating rooms – to solve problems quickly, with little time to consider the long term consequences of a device’s effect on a growing child’s physiology and development.

And while incentives currently exist to promote the development of products for pediatric rare diseases, development in this area continues to lag due to the compounded challenges associated with studying both a rare and pediatric population.

In recognition of these challenges, Congress directed FDA to issue a report and strategic plan focused on accelerating and encouraging the development of therapies for pediatric rare diseases. In response, FDA convened a series of public meetings from January 6 – 8, 2014 to discuss the many challenges in developing treatments for rare diseases, specifically for children with rare diseases, and how to overcome those challenges.  These meetings generated a great deal of interest in the rare disease and pediatric communities. Hundreds of people attended either in person or via webcast and represented a wide swath of these overlapping communities, including patients, academicians, researchers, clinicians, industry, and governmental agencies, many of whom were noted experts in their respective fields.

There were frank, robust and productive conversations on a wide range of topics. A few common themes emerged, especially the important role that patient advocacy groups, including parents of pediatric patients, play in furthering drug development, such as participating in the development of robust patient registries and natural history studies, and providing their perspectives on the risks and benefits of specific treatments. Another common theme was the need for strong collaborations between patients, researchers, industry, and government.

My office, the Office of Orphan Products Development (OOPD), is now coordinating a cross-agency effort with Center for Drugs Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), the Center for Devices and Radiological Health (CDRH), and the Office of Pediatric Therapeutics (OPT) to develop a report and strategic plan to encourage and accelerate the development of therapies for pediatric rare diseases. The goal of this report is to incorporate the valuable insights gained from these public meetings to inform and tailor ongoing and future agency initiatives to more effectively advance the development of such therapies.

OOPD, in collaboration with CDER, is also launching a web-based educational tool for rare disease patients, advocacy groups, researchers and industry on various FDA-related topics. Current topics include the essentials of interacting with FDA and expanded access to products under development. The goal is to continue to add to this educational resource over time. For the new educational tool, as well as additional information, visit the OOPD Educational Resources web page. In addition, FDA and the National Institutes of Health (NIH) will jointly celebrate Rare Disease Day with a one-day program at NIH Masur Auditorium highlighting various rare diseases programs, research activities, and initiatives. For more information about this event that is free and open to the public, and available via webcast, visit the OOPD web page.

The needs of rare disease patients and the pediatric population are complex and pose challenging issues. We are committed to working with the pediatric rare disease community to face those challenges head-on and to accelerate the development safe and effective therapies for these diseases.

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

FDA Commemorates 30th Anniversary of the Orphan Drug Act

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

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

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.

The 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

Advocating for Patients with Rare Diseases

By: Debra Y. Lewis, OD MBA

This week we commemorate the fifth annual Rare Disease Day, a global campaign to raise awareness of the millions of people worldwide who suffer from rare diseases. In the United States, about 30 million Americans have rare diseases, so in reality, rare diseases are not so rare when viewed together as a group.  Because of the recognition of the need for therapies for rare diseases, today FDA held our first-ever Rare Disease Patient Advocacy Day.  

Rare Disease Patient Advocacy Day at FDA March 1, 2012 Stick figures of familes with the in front of the earthFDA designed Patient Advocacy Day to help patients and caregivers engage with us on issues related to drug and medical device development for rare diseases and conditions. Today gives rare disease patient advocates the opportunity to meet with FDA staff and learn more about how FDA works. And, as we come together with colleagues, families, patients and advocacy groups, it gives FDA a moment to reflect on recent news in helping people with rare diseases. 

We often talk about how important the Orphan Drug Act has been in bringing treatments to people with rare diseases – notably children with rare diseases. And we can see its impact. A new study published this week in Pediatrics highlights the progress we’ve made over the past 10 years in bringing treatments to children with rare diseases. The study reports that from 2000 to 2009, 1138 “orphan” drugs were designated and 148 received FDA approval, of which 38 were for pediatric diseases. The proportion of approvals for pediatric products increased from 17.5% in the first half of the decade, to 30.8% in the second. Orphan Drug Act incentives have led to increased product availability for rare diseases overall, with an increasing number of marketing approvals for children in the past decade.

And in 2011, FDA approved 26 drugs and biological products for rare diseases.  About one-third of all new molecular entities approved by the agency were for rare diseases. FDA also approved six medical devices for rare conditions under the Humanitarian Device Exemption program in 2011. We are very proud of the collaborations between industry, patient advocates and FDA that have made this a reality.  

There are over 400 drugs and devices approved for rare diseases and conditions, and millions of lives have been saved or improved with these new products. However, we still have much to do to meet the rare diseases challenge – there are 7000 rare diseases and most are without a current treatment available. Meeting this challenge is the focus of FDA’s Patient Advocacy Day today and will continue to be in the coming years as we strive to improve the lives of all Americans impacted by a rare disease.

Debra Y. Lewis, OD MBA, is Deputy Director of FDA’s Office of Orphan Products Development