FDA Introduces Rare Disease Evidence Principles for Faster Drug Review Process

The FDA has introduced the Rare Disease Evidence Principles (RDEP) to expedite the review of therapies for rare diseases with small patient populations. The process allows sponsors to use alternative evidence, such as mechanistic or biomarker evidence, to demonstrate substantial evidence of effectiveness. Drugs approved under this process may face additional postmarketing requirements to ensure safety and effectiveness. Sponsors can apply to the process before launching a pivotal trial, and requests must be filed before the trial begins.

The U.S. Food and Drug Administration (FDA) has introduced the Rare Disease Evidence Principles (RDEP) to expedite the review of therapies for rare diseases with small patient populations. The new process, outlined by the FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER), allows sponsors to use alternative evidence, such as mechanistic or biomarker data, to demonstrate substantial evidence of effectiveness. This initiative is guided by the specific challenges tied to rare disease research and aims to address the unique needs of these conditions [1].

Under the RDEP, certain rare diseases may qualify for a single-arm trial to serve as pivotal evidence, supported by data from other sources such as evidence of treatment effect on direct pathophysiology, relevant clinical pharmacodynamic data, and case reports. Additionally, confirmatory evidence through appropriate external controls or natural history studies may be considered [1].

To be eligible for the RDEP process, the investigational medicine must target the specific genetic defect underlying the disease. The drug must be intended for an ultra-rare condition affecting fewer than 1,000 Americans, and the disease should be marked by progressive deterioration in function before rapid and significant disability or death. There must also be no available alternative therapies that sufficiently alter the course of the disease [1].

The FDA has been working on this new pathway for rare diseases, with former CBER director Peter Marks, M.D., Ph.D., playing a significant role in its development. The proposal follows Marks’ efforts to adjust regulatory pathways for investigational rare disease treatments. The FDA commissioner Marty Makary, M.D., also announced plans for this new pathway in an April episode of the Megyn Kelly Show [1].

In August, the FDA approved four new therapies for rare diseases, demonstrating the agency’s commitment to advancing treatments for these conditions. Jazz Pharmaceuticals’ Modeyso was approved for diffuse midline glioma with an H3 K27M mutation, while Insmed’s Brinsupri was approved for non-cystic fibrosis bronchiectasis. Precigen’s Papzimeos was approved for recurrent respiratory papillomatosis, and Ionis Pharmaceuticals’ Dawnzera became the first RNA-targeting prophylactic for hereditary angioedema (HAE) [2].

The introduction of the RDEP process is expected to streamline the approval process for rare disease therapies, potentially leading to faster access to life-saving treatments for patients with these conditions.

References:
[1] https://www.fiercebiotech.com/biotech/fda-proposal-would-allow-single-arm-trials-confirmatory-evidence-ultra-rare-diseases
[2] https://www.biospace.com/fda/rare-diseases-secure-four-fda-firsts-in-august