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FDA Insight: Rare Diseases and Orphan Products

Dr. Shah welcomes Dr. Janet Maynard, director of FDA’s Office of Orphan Products Development, for a discussion on the agency’s work advancing evaluation and development of products that demonstrate promise for the diagnosis and treatment of rare diseases.

FDA Insight: Episode 20 – Transcript

>> Anand Shah: Welcome back to another episode of FDA Insight. I'm Dr. Anand Shah, the Deputy Commissioner for Medical and Scientific Affairs here at the FDA. Thank you so much for joining us for another great episode.

This week, we'll be discussing FDA efforts to facilitate the development of treatments for rare diseases.

My guest today is Dr. Janet Maynard, the director of the Office of Orphan Products Development, or OOPD, as it's known at FDA. Dr. Maynard oversees the legislatively mandated designation and grant programs intended to promote the development of products for rare diseases, including orphan drug, rare pediatric disease, and humanitarian use device designation programs, as well as clinical trial, natural history study and pediatric device consortia grant programs.

In her role, she serves as FDA's lead in coordinating crosscutting rare disease issues and engages extensively with patients, sponsors, and other key stakeholders.

Dr. Maynard, welcome to FDA Insight.

>> Janet Maynard: Thank you for having me.

>> Anand Shah: Well, let's jump right in. This week's podcast is about rare diseases and the orphan product process. Can you explain to our listeners what is a rare disease and what are some examples of rare diseases?

>> Janet Maynard: Sure, the law and FDA define a rare disease or condition as one that affects less than 200,000 persons in the United States or meets cost recovery provisions described in the law. Scientists have identified nearly 7,000 rare diseases, ranging from rare cancers to metabolic diseases. In the United States, it is estimated that up to 30 million people, or one out of every 10 Americans, have at least one rare disease.

Thus, while rare diseases are individually rare, collectively they are not. Tragically, more than half of these people are children. There are many different types of rare diseases, and while many rare diseases are thought to be genetic, other rare diseases are not inherited, and may result from a variety of causes, such as infections or environmental causes. Some examples of rare diseases include cystic fibrosis, sickle cell disease, systemic sclerosis, Duchenne muscular dystrophy, and tenosynovial giant cell tumors.

Rare diseases can be serious and life threatening and have profound impact on people and their families.

>> Anand Shah: What is the Orphan Drug Act and why is it needed?

>> Janet Maynard: The Orphan Drug Act, also known as the ODA, incentivizes the development of medical products to treat rare diseases. Specifically, part of the Orphan Drug Act provides for granting a special designation status to a drug or biological product to treat a rare disease or condition upon request of a sponsor. The orphan drug designation status is a key link to the ODA incentives.

Thirty-eight years ago, there were few drugs and fewer devices to treat rare diseases. Some rare disease treatments had been orphaned or discontinued because there was not enough incentive to continue development or production. Thus, to spur drug development, congress enacted the Orphan Drug Act and it was signed into law in 1983. In 1990, separate legislation was passed establishing a rare disease path to market for medical devices.

>> Anand Shah: So, Dr. Maynard, when and how does a drug receive orphan drug designation?

>> Janet Maynard: Any time before a sponsor submits a marketing application to FDA, the sponsor can request orphan drug designation, and FDA will grant such designation if the request meets specific criteria. The criteria include factors such as adequate documentation that the disease is rare, and sufficient scientific rationale to establish a medically plausible basis for expecting the drug to be effective in the rare disease. Orphan drug designation requests are first evaluated by our OOPD intake staff members and then reviewed by OOPD medical professionals and scientists, such as physicians and pharmacists, to see if the drug designation request meets all the criteria.

When reviewing a request for orphan drug designation, the FDA considers the mechanism of action of the drug to determine what distinct disease or condition the drug is intended to treat, diagnose, or prevent. Whether a given medical condition constitutes a distinct disease or condition for the purposes of orphan drug designation, depends on several factors assessed together, including the clinical development of the disease or condition, the likely course of the disease or condition, and resistance to treatment. During review of an orphan drug designation request, OOPD may consult with the medical product centers at FDA. If a drug receives orphan drug designation, the designation is included on FDA's external website.

>> Anand Shah: What are the incentives associated with an orphan drug designation?

>> Janet Maynard: Orphan drug designation qualifies the drug sponsors for various development incentives, including tax credits for qualified clinical testing, a waiver of the prescription drug application user fee, and the potential to receive seven years of orphan drug market exclusivity upon approval. This orphan drug exclusivity means that FDA will not approve that same drug for that same approved orphan indication. However, FDA can approve that drug for other indications and can approve other drugs for that specific rare disease indication. In addition, clinically superior drugs will not be blocked by that orphan drug exclusivity.

>> Anand Shah: Let's discuss outcomes and results. Has the Orphan Drug Designation Program incentivized companies to develop treatments for rare diseases?

>> Janet Maynard: Yes, it has. Since the passage of the Orphan Drug Act, we've made significant progress. Over the last 38 years, drugs and biologics have been developed and approved for over 900 rare disease indications. As a side note, under the Humanitarian Use Device Program, over 75 devices have received approval to treat or diagnose a disease or condition that affects not more than 8,000 people in the U.S. per year.

Thus, we have made progress in the development of treatments for rare diseases. However, the majority of rare diseases still do not have approved therapies, and more work is needed to help people with rare diseases. FDA's work to advance treatments for rare diseases remains a top and important priority.

>> Anand Shah: After a drug receives orphan drug designation, does the drug become available at pharmacies for patient use?

>> Janet Maynard: Thanks for asking that question. A new drug does not become available at pharmacies for patient use immediately after it receives orphan drug designation. Orphan drug designation will provide incentives for sponsors to study promising new drugs for rare diseases. However, it is after the new drug has been studied and approved by the FDA, that the approved drug becomes available for the rare disease use.

>> Anand Shah: Let's talk about some of your office work at the FDA. How is the agency modernizing the orphan drug process?

>> Janet Maynard: Well, first, the focus of our technological enhancements is to support the development of safe and effective treatments for rare disease patients and families. The enhancements improve collaboration, which is essential to supporting rare disease product development.

For example, collaboration through our outreach activities is an important aspect of our work in OOPD. In addition, technology is an essential tool to support collaboration both with our FDA colleagues and with those submitting designation requests. Orphan drug technology modernization effort will strengthen the information technology processes and review in OOPD. These efforts include the implementation of a new internal orphan drug designation workflow management tool and an orphan drug designation portal.

The portal, which just went live, allows electronic submission of a new orphan drug designation request through a cloud-based online submission portal. Moving from a paper-based process to a cloud-based submission portal provides drug developers with enhanced direct communication with the FDA regarding each submission. The orphan drug technology modernization efforts allow for more connected information technology system, advanced analytics, and improvements in knowledge management.

Technological enhancements are important to supporting FDA's mission to advance the evaluation and development of safe and effective treatments for people with rare diseases.

>> Anand Shah: Are there other ways by which the FDA supports rare disease medical product development?

>> Janet Maynard: Developing a treatment for a rare disease is a team sport and a team effort. At FDA, we work with both internal and external rare disease stakeholders to ensure optimal rare disease product development. FDA has many initiatives and programs that support rare disease product development, and I will focus on programs in the Office of Orphan Products Development.

The Office of Orphan Product Development has three core program areas: designations, grants, and outreach.

Today, we are discussing the first two core programs, designations and grants. The designation program has three components, orphan drug designation, rare pediatric disease designation, and humanitarian use device designation. We've already discussed orphan drug designation and briefly mentioned humanitarian use devices. The rare pediatric disease designation program uses a different incentive approach that is related to a pediatric voucher program. The program is intended to encourage development of new drugs and biological products for rare pediatric diseases. The Humanitarian Use Device Program designates medical devices intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year. Humanitarian use device designation will allow the sponsor to apply for a different marketing approval path, called the Humanitarian Device Exemption Pathway.

Our grant program has three components. The Orphan Products Clinical Trials and Natural History Program provides funding for clinical trials and natural history studies that advance rare disease medical product development. The Pediatric Device Consortia, or PDC Grant Program, provides funding to develop nonprofit consortia to facilitate pediatric medical device development.

>> Anand Shah: With the label rare disease, how busy is OOPD? Do you just focus on a few diseases?

>> Janet Maynard: OOPD work covers the full spectrum of rare diseases, not just a few diseases. This year has been extremely busy in terms of the volume of orphan drug and rare pediatric disease designation requests. Year to date, in October, OPD had approximately a 50 percent increase in orphan drug designation requests and an approximately 500 percent increase in rare pediatric disease designation requests compared to the prior year at the same time.

In addition to our designation work, we continue our important work related to funding rare disease research. This October, the FDA awarded six new clinical trial research grants to principal investigators from academia and industry, totaling over $16 million over the next four years. These grants will enhance the development of medical products and treatments for people with rare diseases. These awards focus on unmet needs, including for diseases such as Stargardt disease, pancreatic cancer, and graft versus host disease.

>> Anand Shah: Dr. Maynard, how is FDA supporting rare disease product development during the COVID-19 pandemic?

>> Janet Maynard: Developing a product for a rare disease is challenging. While the current public health emergency is adding additional challenges, FDA is working on strategies and solutions to address these challenges. Rare disease therapy development remains a priority at FDA during COVID-19. This year, researchers studying rare diseases and their treatments face new challenges and may face increased costs for clinical trials due to the COVID-19 pandemic. To help alleviate this, OOPD provided existing grantees with additional funding. These new resources allow ongoing studies to implement necessary steps to allow their research to continue, and assure the safety of study participants, to maintain compliance with good clinical practice, and to minimize risk to trial integrity.

We know the rare disease community, including people with rare diseases and their families, have been profoundly impacted by COVID-19. During this challenging time, FDA remains committed to supporting the development of treatments for people living with rare diseases and continues to work with rare disease stakeholders.

>> Anand Shah: Dr. Maynard, you've shared a ton of helpful information for our listeners. As we wrap up, I want to thank you for taking the time to join us this week on FDA Insight. And thank you for all that you do to support public health.

>> Janet Maynard: Thank you again for having me. I've had a great time.

>> Anand Shah: In the weeks ahead, we'll be covering a variety of topics that are important to public health. As always, we'll be providing you insight in plain language to help you understand the products that we regulate, the issues that we face, and the processes that we follow.

We hope you enjoyed this episode of FDA Insight. Please subscribe on your favorite podcast app, such as Apple Podcasts, Google Podcasts, Spotify, and Pandora. Thanks for listening.

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