The Food and Drug Administration rejected a gene therapy Regenxbio has been developing for a rare disease called Hunter syndrome, in a decision that marks the latest blow for a field that has seen multiple recent regulatory setbacks in the U.S.
In a statement Monday, Regenxbio said the FDA issued a so-called complete response letter for its treatment, known as RGX-121. The agency had until Feb. 8 to make a decision and, prior to that date, Regenxbio believed it addressed questions the regulator had about the evidence supporting RGX-121’s effectiveness.
However, the FDA ultimately decided that, while it agreed “in principle” to the design of the clinical trial Regenxbio built its application around, multiple issues with its results persisted. The regulator wasn’t convinced by the surrogate measure Regenxbio used to assess the treatment’s effectiveness, and was skeptical of the study’s comparisons between historical data and the group receiving the therapy.
The FDA’s letter “lists several potential paths forward,” such as running a new trial, using an untreated control group, or treating more patients with longer follow-up. But Regenxbio noted that all of those options “would be challenging” in an uncommon condition like Hunter syndrome. The company will request a meeting with the FDA to discuss the letter and the path towards a resubmission.
"We are concerned about FDA's feedback regarding the overall development path and evaluation of the data in the context of the urgent need for this irreversible ultra-rare disease,” Curran Simpson, Regenxbio’s CEO, said in a statement.
The rejection comes a week after the FDA placed clinical holds on RGX-121 and a separate therapy for a different rare disease, Hurler syndrome, when a treated study participant with the latter condition developed a brain tumor. The FDA extended the hold to both products because of certain similarities, as well as a “shared risk” between the two studies.
Regenxbio has countered that no causal link was established and no similar issues were identified in all of the 32 trial participants who have received RGX-121. Still, the ensuing rejection is “not surprising” given the study suspension, and now leaves the company “with a long delay to approval,” wrote Leerink Partners analyst Mani Foroohar.
Regenxbio shares fell by double digits in early trading Tuesday.
Under Commissioner Martin Makary, the FDA has stressed an intent to be more flexible in reviewing genetic medicines for rare conditions. It outlined a new “plausible mechanism” pathway tailored to treatments for such diseases, and published draft guidance meant to support speedier research.
But that messaging has at times conflicted with agency’s decisionmaking. The office that regulates gene and cell therapies is now run by Vinay Prasad, a contrarian voice who’d been critical of some fast-tracked treatments. Since he’s taken over that office, at least some gene and cell therapy makers have claimed the agency changed its stance compared to previous guidance.
UniQure, which is developing a gene therapy for Huntington’s disease, said the agency made a “key shift from prior communications” in suggesting that its treatment wasn’t yet approvable. Capricor Therapeutics, which is making a cell therapy for Duchenne muscular dystrophy, was similarly turned back after agency reviewers questioned its efficacy data.
The latter company has since published fresh data that it hopes to support a new submission.
