FDA Proposes New Path to Approval of Therapies for Ultra-Rare Diseases: Relying on Mechanism of Action

FDA Proposes New Path to Approval of Therapies for Ultra-Rare Diseases: Relying on Mechanism of Action

FDA Commissioner Dr. Martin Makary has proposed introducing a new conditional approval mechanism for drugs intended for ultra-rare and incurable diseases for which large-scale clinical trials are impossible.

The essence of the approach:

If a drug has a scientifically sound, physiologically plausible mechanism of action (plausible mechanism), it can receive approval conditionally, without completed RCTs. Systematic monitoring of all patients and collection of real-world data / real-world evidence becomes a mandatory requirement.

“When a disease affects several dozen people, conducting classical studies becomes impossible. If we have a potentially effective drug and a logical mechanism of action, we should give patients a choice"

 — Makari noted. 

He also emphasized that 

the use of therapy will be based on the voluntary decision of the patient and doctor, with informed consent.

What is changing?

The approach can provide accelerated access to therapy while monitoring its effectiveness and safety - through registered observations. This is especially relevant in situations where there are no alternative treatment options.

Limitations and risks

The proposal has not yet been formalized as an official mechanism or legislative initiative.

Experts emphasize the need for:

• clear criteria for assessing the validity of the mechanism of action,

• regulations for compensation and legal liability with a limited evidence base,

• regular collection and analysis of RWE as an integral part of the model.

Read more: BioSpace (https://www.biospace.com/policy/makary-discusses-expedited-rare-disease-approvals-pathway-public-dis...)