Agency’s planned framework is the first to support the approval process for new ultra-rare disease treatments.
US plans to provide pharma and biotech companies with a new regulatory pathway for the approval of ultra-rare disease treatments has progressed with the publication of draft guidance on the topic.
The Plausible Mechanism Framework from the US Food and Drug Administration (FDA) covers submissions that provide “substantial evidence of effectiveness and safety when randomised controlled trials are not feasible due to small patient populations”.
While the guidelines focus on genome editing and RNA-based therapies such as antisense oligonucleotides, they could be applicable to additional tailored therapies as long as they directly address the underlying specific cause of the disease, FDA stated.
Chief Medical and Scientific Officer and Center for Biologics Evaluation and Research Director (CBER) Dr Vinay Prasad said: “Designing treatments unique to individual patients has always been the promised goal of personalised medicine.
“After 25 years the FDA has, for the first time, outlined a framework to facilitate these approvals. The Plausible Mechanism Framework is a revolutionary advance in regulatory science.”
In the draft guidance, relevant therapies are those that are designed to correct or modify the underlying cause of disease.
Key criteria include:
- Identifying the disease-causing abnormality
- Demonstrating the therapy targets the root cause or proximate biological pathway
- Relying on well-characterised natural history data in untreated patients.
- Confirming successful target drugging or editing
- For traditional approval, therapies should demonstrate improvement in clinical outcomes, disease course or biomarkers if they are established to predict clinical benefit.
FDA noted that a product targeting different mutations in a single gene is appropriate for inclusion in a single product application. It would then be potentially assessed via master protocols that evaluate these product variations in a single trial.
A highly supported ‘plausible’ mechanism of action may then be used to support the addition of other such genome editing product variants, intended to treat patients with mutations that were not included in the clinical trial used to support the original approval"
“A highly supported ‘plausible’ mechanism of action may then be used to support the addition of other such genome editing product variants, intended to treat patients with mutations that were not included in the clinical trial used to support the original approval,” the agency said.
Dr Tracy Beth Høeg, Acting Director for FDA’s Center for Drug Evaluation and Research, added: “We anticipate our Plausible Mechanism draft guidance will inspire industry to place increased focus on individualised therapies, thereby driving innovation, improving safety, lowering costs and offering more patients with ultra-rare diseases a unique shot at a life-saving treatment.”
Public comment on the draft guidance can be submitted to regulation.gov.
FDA also recently shared details of a new drug approval policy with criteria for clinical trial requirements.
