FDA Reversals on Rare Disease Drugs Spark Investor Uncertainty
The FDA has denied or discouraged at least eight drug applications in the past year, including treatments for rare diseases, raising concerns about regulatory consistency and the future of experimental therapies.
The FDA in the past year has denied or discouraged the applications of at least eight drugs, according to RTW Investments, including a gene therapy for Huntington's disease from UniQure, a gene therapy for Hunter syndrome from Regenxbio and a drug for a blood condition from Disc Medicine. The agency initially refused to review Moderna's flu shot before reversing course.
In each case, the FDA took issue with the evidence the companies were using to support their applications. Some of the studies didn't test the drugs against a placebo. Some companies didn't directly measure the drug's efficacy, instead relying on other factors like biomarkers to predict how well the treatment might work.
In every case, the companies have accused the FDA of reversing its previous guidance. That's making investors wary that a more unpredictable FDA could jeopardize the future of other treatments for hard-to-treat diseases.
In the case of UniQure, the FDA asked the company to run a new study that directly compares its treatment to placebo. UniQure said that contradicts the agency's past guidance that the company could seek approval with trial data that compared UniQure's treatment to an external database of people with Huntington's disease.
One looming decision is a drug candidate from Denali Therapeutics for Hunter syndrome, a rare disease that causes physical defects like hearing loss and joint problems, as well as cognitive issues. The company's application for accelerated approval relies on a trial that wasn't randomized and data showing the drug decreases levels of a biomarker associated with the condition. The FDA delayed its review of the application by three months and is now expected to decide by April 5.
Other companies being watched include Dyne Therapeutics, which is advancing a drug for Duchenne muscular dystrophy; Taysha Gene Therapies, which is developing a gene therapy for Rett syndrome; Wave Life Sciences, which is working on a treatment for a liver condition; and Lexeo Therapeutics, which is developing a gene therapy for Friedreich Ataxia. All of those companies' stocks are down this year.
A Dyne spokesperson said the company has maintained a frequent, positive and collaborative dialogue with a consistent set of reviewers over the past 18 months, and that it's confident in its development strategy and path forward based on the strength of its clinical results, rigor of its trial design and continued engagement with the FDA.
In a statement, Denali Therapeutics CEO Ryan Watts said the company continues having constructive discussions with the FDA, and it's confident in the strength of the data package it submitted.
In recent years, the FDA appeared willing to accept drugs for rare diseases that showed promise in less rigorous studies than the gold standard randomized, double-blind placebo controlled trials. That meant helping bring treatments more quickly to patients who have conditions where time passing could mean the loss of functions like walking or talking, or even death.