FDA proposes new system for approving customized drugs and therapies for rare diseases

Federal health officials unveiled a groundbreaking proposal Monday aimed at accelerating the development of customized treatments for patients suffering from hard-to-treat diseases, including rare genetic conditions that pharmaceutical companies have historically avoided due to limited profitability.

The Food and Drug Administration’s preliminary guidelines would establish a new regulatory pathway for therapies tested in only a small number of patients—a necessity when dealing with extremely rare conditions that make traditional large-scale clinical trials impractical. While the FDA announcement specifically mentions gene editing technologies, agency officials indicated the approach could extend to various drugs and therapeutic modalities.

This policy shift represents a significant victory for rare disease patients, advocates, and researchers who have long argued that these conditions are poorly served by both the pharmaceutical industry’s business model and the FDA’s conventional approval framework.

“It is our priority to remove barriers and exercise regulatory flexibility to encourage scientific advances and deliver more cures and meaningful treatments for patients suffering from rare diseases,” FDA Commissioner Marty Makary said in a statement accompanying the announcement.

The proposal comes just one week after Commissioner Makary revealed the agency would abandon its longstanding requirement for two clinical trials in standard drug reviews. This marks the latest in a series of significant changes to FDA protocols, many of which have bypassed the formal federal procedures typically used when updating agency regulations.

When questioned about these procedural irregularities, senior FDA officials maintained that recent changes, including Monday’s proposal, do not constitute new FDA standards. The agency will accept public comments on the draft guidance for 60 days before proceeding with finalization.

Recent scientific breakthroughs have demonstrated the potential of personalized genetic treatments. Last year, researchers at Children’s Hospital of Philadelphia and the University of Pennsylvania successfully developed a CRISPR-based therapy—utilizing the Nobel Prize-winning gene editing technology—to treat an infant born with a rare disorder causing dangerous ammonia accumulation in the bloodstream.

The FDA’s traditional approach requires pharmaceutical companies to demonstrate safety and efficacy through rigorous clinical studies comparing patients receiving the experimental therapy against those given a placebo or alternative treatment. Larger patient populations generally yield more statistically robust evidence.

However, for ultra-rare conditions affecting perhaps a dozen people worldwide, drug companies face little financial incentive to invest the hundreds of millions of dollars required to complete studies and navigate the FDA approval process—a journey that can span a decade or longer.

The newly announced “plausible mechanism” pathway would streamline authorization for experimental treatments while offering companies the crucial ability to commercialize their therapies. This represents a significant advancement beyond the FDA’s existing “compassionate use” program, which allows access to experimental drugs for patients without alternatives but prohibits companies from profiting from treatments not yet fully vetted by the agency.

The pathway’s name refers to the scientific criteria regulators will require before approving experimental therapies. FDA officials emphasized this approach will be reserved for conditions with well-understood mechanisms where there exists a plausible scientific rationale suggesting the therapy will effectively address the underlying genetic or cellular biology of the disease.

Researchers must also demonstrate that their intervention successfully targets the patient’s specific genetic or biological abnormality—evidence that the treatment is working as intended at a molecular level.

For the estimated 30 million Americans living with rare diseases—approximately 95% of which have no FDA-approved treatments—this regulatory innovation could significantly accelerate access to potentially life-changing therapies that might otherwise never reach development.

The pharmaceutical industry and patient advocacy organizations will closely monitor the proposal’s progression through the comment period, as its implementation could fundamentally reshape how treatments for the rarest conditions reach those who need them most.