Rare Diseases
Cardiovascular and Renal Drugs Advisory Committee will consider whether open-label extension data from a randomized trial that failed its primary endpoint, along with a historical control comparison, are enough to support approval in the ultra-rare disease.
The US FDA commissioner also said the hub is looking for an executive director who will work with the CBER and CDER heads, who will serve as co-leads.
Under current law, drugs or biologics must receive rare pediatric disease designation before 1 October to be eligible for a priority review voucher. The sunset provisions have led to a spike in designation requests at the FDA and a push by pediatric and rare disease advocates for an extension, either through a continuing resolution or reauthorizing legislation.
A real-world evidence study also does not meet the regulatory standard for an adequate and well-controlled clinical investigation, the agency said. The FDA should allow the accelerated approval drug to remain available like other treatments that failed their confirmatory trials, Intercept said.
Amid a push for new incentives, the US FDA’s Kerry Jo Lee, associate director for rare diseases in the Center for Drug Evaluation and Research’s Office of New Drugs, said in an interview with the Pink Sheet that the tools ultra-rare sponsors need already are available.
Pink Sheet reporter and editors discuss former Surgeon General Jerome Adams’ views on how the FDA can better ensure clinical trial diversity, questions about approving a new drug that would be used with a standard of care regimen that is off-label, and the agency beginning to schedule fully in-person advisory committee meetings.
Determining the efficacy of arimoclomol alone in Niemann-Pick disease type C was challenging because most study subjects also received miglustat, an off-label drug in the US. An FDA official said panelists should assess arimoclomol’s efficacy as it was studied in the pivotal trial.
The pivotal trial results, along with other data, support a conclusion of efficacy for Niemann-Pick disease type C, but nonclinical data are weak and cannot serve as confirmatory evidence for a single trial, the advisory committee majority said.
Overreliance on “problematic” trials while overlooking the value of real-world evidence could affect the development of other rare disease treatments, according to Advanz’s CEO.
The US FDA’s Genetic Metabolic Diseases Advisory Committee will comprise three regular voting members and 13 temporary members, including some adcomm veterans, when it reviews Zevra Denmark’s arimoclomol for Niemann-Pick disease type C.
High patient expectations also drove Telethon’s decision to bring forward its marketing authorization application plans for its ultra rare disease gene therapy, etuvetidigene autotemcel.
The US FDA seeks input on the validity of the clinical outcome scale used in the sole pivotal trial, whether treatment benefit can be ascertained, and the robustness of the confirmatory evidence in Niemann-Pick disease type C.
Editors from the Pink Sheet and Medtech Insight discuss the retirement of Jeff Shuren, PBM executives again appear unscathed after another Capitol Hill appearance, and the growing push to ensure the FDA’s rare pediatric disease priority review voucher program is renewed.
As the reauthorization deadline nears, CDER and CBER leaders stressed that sunsetting the program would hurt pediatric rare disease development, while endorsing a new Democrat-proposed stick for rare disease research.
Relyvrio/Albrioza, Amylyx’s ill-fated treatment for amyotrophic lateral sclerosis, was approved for marketing by the US Food and Drug Administration but rejected by the European Medicines Agency. The Pink Sheet explores how the two agencies applied the available regulatory flexibilities and the impact of other factors, such as regulatory precedence and patient influence, on decision-making.
Senior leadership in the FDA’s drugs, biologics and devices centers want reviewers to feel more comfortable taking risks in product approvals, but may need more concrete examples of regulatory flexibility's success to convince them.
Most of the new Genetic Metabolic Diseases Advisory Committee members have little FDA or advisory committee experience, except the new industry representative, with six more voting slots still to fill before its first meeting.
Establishing multi-site network centers for rare diseases can help advance clinical research, but “onerous” regulatory compliance issues are a barrier that must be overcome, a clinical academic says.
The head of CBER's Office of Therapeutic Products also touted hiring achievements and new communication plans with sponsors at an Alliance for Regenerative Medicine meeting.
A prominent rare disease researcher has praised the UK’s Department for Health and Social Care for its transparency and willingness to work with experts, but said that regulatory systems needed to speed up to facilitate patient access to innovative treatments.