FDA introduces process to ease review of rare disease therapies
Aim is 'common-sense approach' for treating AADC defiency, other conditions
The U.S. Food and Drug Administration (FDA) has introduced a process it says will ease and speed the regulatory approval of therapies for very rare diseases — such as aromatic l-amino acid decarboxylase (AADC) deficiency — that have a significant unmet medical need and a known genetic cause.
This new process will use the RDEP, fully, the Rare Disease Evidence Principles, which were developed jointly by the FDA’s Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER).
The RDEP outlines the types of evidence that can support regulatory approval for rare disease treatments — needed because standard clinical trial data like those used for more common diseases are more challenging to collect. According to the FDA, therapy developers can apply for a treatment to be reviewed through the RDEP process if it meets specific criteria.
“Drug developers — and the patients they hope to treat — deserve clear, consistent information from the FDA,” Marty Makary, MD, the FDA commissioner, said in an agency press release that detailed some of the new criteria.
This process will “ensure that FDA and sponsors are aligned on a flexible, common-sense approach within our existing authorities,” Makary said.
In the U.S., a rare disease is defined as a condition affecting fewer than 200,000 people. AADC deficiency is extremely rare, with approximately 350 cases reported worldwide..
People with the genetic disorder lack enough functional aromatic l-amino acid decarboxylase, which is an enzyme needed to produce critical brain signaling chemicals. The condition leads to a range of neurological symptoms, including abnormal eye movements, sleep problems, and diminished motor abilities.
Treatment development hampered by small numbers of patients
Therapeutic development for rare diseases like AADC deficiency is complicated by the fact that very few patients are available to participate in clinical studies. This can make it difficult for companies to design standard clinical trials that generate sufficiently meaningful safety and efficacy data to support regulatory approval.
Recognizing that there’s a need for alternative, yet still rigorous, methods for evaluating rare disease therapies, the FDA developed RDEP. The principles aim to give drug developers clearer guidance on the types of evidence that can be used to demonstrate a therapy’s effectiveness.
[This process ensures] … that [the FDA incorporates] confirmatory evidence to give sponsors a clear, rigorous path to bring safe and effective treatments to those who need them most.
They stipulate that regulatory reviews for eligible rare disease therapeutics will consider additional supportive data beyond typical clinical trial outcomes.
According to Makary, “these principles ensure that … [the FDA incorporates] confirmatory evidence to give sponsors a clear, rigorous path to bring safe and effective treatments to those who need them most.”
An approval may be based on findings from one adequate and well-controlled clinical trial, supplemented by other robust confirmatory evidence. That could include clinical biomarker or pharmacological data and preclinical studies, as well as findings from case reports, expanded access programs, or natural history studies.
New FDA process will feature closer collaborations
To be eligible for review through RDEP, investigational therapies must be designed to address the needs of a very small rare disease group in the U.S. — generally fewer than 1,000 people — who are facing rapid functional deterioration leading to disability or death and who have no adequate alternative therapies.
The treatment must also specifically address the relevant genetic defect that causes the disease.
Therapy sponsors can apply for their candidate treatment to be reviewed under RDEP any time before a pivotal clinical trial intended to support the regulatory application is launched.
The sponsors will then work closely with the FDA to define precisely what evidence is needed for approval in that particular case. Patient and expert input during this process is encouraged, according to the FDA.
Overall, the RDEP process aims to guide faster and more predictable regulatory reviews of these rare disease therapies. If a treatment is approved through RDEP, the FDA says there may be additional postmarketing requirements to further establish its safety and effectiveness.
The FDA noted that its orphan drug program, which gives financial and regulatory incentives to expedite the development of treatments for rare diseases, is entirely separate from RDEP. A therapy reviewed under RDEP does not necessarily earn orphan drug status, and vice versa.
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