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Predicting the Rare Disease Pipeline: FDA Panel Identifies Trends & Challenges

A panel of members from the US Food and Drug Administration (FDA) sat down to discuss the influential factors and projective trajectory of the rare disease pipeline.

Predicting the pipeline for upcoming therapies is an area of focus for the rare disease community, which is why a panel of members from the US Food and Drug Administration (FDA) sat down to discuss the influential factors and projective trajectory of the rare disease pipeline at this year’s National Organization of Rare Diseases’ Rare Diseases & Orphan Products Breakthrough Summit (NORD Summit 2018).

A heavy focus at the summit in general, patient involvement in the drug development process was reiterated by the panel.

“Patients are our partners, and they are our customers,” Jefferey Shuren, MD, JD, director of the Center for Devices and Radiological Health, said.

To this end, the FDA staff strives to engage with patients as much as possible. In fact, 3 years ago, the FDA set a goal to have 90% of its staff participate in engagement efforts with patients over a 2-years timespan. They were able to do even better than that—after 2 years’ time, 96% of the FDA staff reported having had interactions with patients, even secretaries.

Another effort made by the FDA to encourage patient involvement was the decision to create a Patient Engagement Advisory Committee that includes patient a patient focus. The committee consists of 9 voting members, including the chair, who are versed in clinical research, primary care patient experience, and the health care needs of patient groups in the US.

“Patients help maintain a sense of urgency and keep in mind what matters, Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research, added.

Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, emphasized that patient involvement in drug development has evolved for the better as patients have invested in translational research, encouraged others to enroll in trials, and spoken with companies to relay the kinds of information that is important to consider and include in clinical trials. As such, patients are largely influential when it comes to identifying which endpoints to consider in a trial or study.

Due, in part, to the lack of medical experts in rare diseases, the FDA panel also noted the increasing focus on formal patient-reported outcomes.

“We now are moving towards more formal patient-reported outcomes and observer-reported outcomes, and part of the guidances that we are going to be issuing will be how to develop and qualify those,” said Dr. Woodcock. “I think we are going to see a real explosion in understanding in these diseases because we are asking people across multiple domains instead of just focusing on 1 measure.”

Patient involvement changes the old idea that “the doctor knows best,” she added. “Now, the patient-doctor relationship is more of partnership, and the patients are experts of sorts in their disease.”

As gene therapy is becoming a more heavily focused therapeutic area in rare diseases, the panel also spoke on efforts being made to ensure it is investigated as a potential therapeutic option for rare diseases.

Primarily, the panel discussed the 6 guidances issued for gene therapies issued by the FDA in July 2018. Of those 6 guidance documents, 3 cover hemophilia, retinal disorders, and rare diseases overall, respectively.

“Today, there are 3 approved gene therapies in the United States,” Dr. Marks added. “There is tremendous interest in this area. There are over 700 active gene therapy investigational new drug applications (INDs) in house. This year, there will most likely be a 40% to 50% increase in that area.”

The panel added that there will likely be more guidance documents issued as well, and that existing guidances will likely be revised as gene therapies and technology progress.

The panel noted that one of the biggest challenges faced when it comes to the development of effective gene therapies has to do with developing manufacturing technology that can keep pace with scientific progression. Manufacturing technology is greatly limited right now, and contract manufacturing capacity is limited—even with rare diseases.

“The entire field is struggling with a crisis in developing the manufacturing technologies here [the US],” said Dr. Marks. “We are very limited right now in manufacturing technologies, and so 1 of our efforts is to help the field by helping manufacturing technologies advance because right now that is limiting the development of these therapies.”

The all-time high of approved orphan drugs was also addressed, which Dr. Woodcock partly chalked up to the data that is now available on the human genome level, which helps better identify causes of diseases as well as appropriate interventions.

With this data now available, part of the pharmaceutical industry is now moving to the narrow populations, like rare disease. Since they are acquiring this data that can better indicate what’s wrong in diseases, they can be better can be better understood, and potential treatments have a better probability of leading to a real treatment effect. Clinical trials also become easier in that sense.

However, a major issue is that companies, such as specialty pharmaceuticals, are targeting small populations, and those companies face high expenses, which result in high costs for everyone.

Dr. Marks added that while the science is exciting and on a quick path, the buyer’s assistance and cost assistance is very slow and lagging. Drug access is also a real concern due to the high price tag. If a therapy is approved, efforts need to be made to ensure that patients have access to the treatment.

Despite the many challenges faced in the rare disease space, the treatment landscape is rapidly evolving, with more potential treatment options being evaluated every day. With the FDA working on improving regulatory aspects of the drug development process, advocacy organizations boosting awareness of these diseases, and patients getting actively involved in the research being conducted, the hope is that the rare disease pipeline will continue to grow.