Shares of REGENXBIO declined 37% on a mixed data readout and other updates from the company’s first quarter earnings call Thursday.
REGENXBIO has linked its Duchenne muscular dystrophy gene therapy to functional improvements in a portion of a Phase 3 program, but two serious adverse events made for what Leerink Partners called a “mixed bag.”
“Bigger picture, the update is more mixed than we had hoped as two [serious adverse events] and lack of certainty on FDA position will likely become the source of debate,” Leerink wrote on Thursday morning.
The analysts were also concerned about the timing of a potential market debut for the gene therapy, called RGX-202. Previously, the company had expected an FDA filing to occur this year, but Thursday’s announcement did not mention plans to submit to the agency, and simply stated that they still expect the product to be approved and launch in 2027.
REGENXBIO also released first quarter earnings on Thursday, providing updates on other recent events including the lifting of a clinical hold and an FDA rejection appeal. The biotech’s shares declined 37% to $6.20 on the flurry of news in pre-market trading.
On the data, REGENXBIO reported the results from the Phase 3 portion of the AFFINITY DUCHENNE trial, which spans Phases 1 through 3. The trial included ambulatory boys aged one or older. RGX-202 met the primary endpoint, which was the proportion of patients who achieved at least 10% microdystrophin expression at week 12. Microdystrophin is used in gene therapy to provide a small, functional version of the dystrophin gene.
REGENXBIO reported that 93% of the 30 patients achieved this goal, with microdystrophin expression averaging 71% across the participants. In boys above 8 years old, which is typically when decline begins to happen, expression was just over 42%. The company said that 80% of patients achieved 40% expression.
The microdystrophin expression was linked with a statistically significant improvement in function, which should support an accelerated application with the FDA, REGENXBIO said.
But two patients experienced serious adverse events; there was one case of liver injury and another of myocarditis, or inflammation of the heart. While the company said that both cases were “easily managed and resolved within weeks,” Leerink told investors that the events “muddy the update.”
REGENXBIO will now head to the FDA for a pre-BLA filing meeting. The biotech plans to submit RGX-202 for accelerated approval based on microdystrophin expression as a surrogate endpoint. Whether the FDA will accept this, however, remains unclear. REGENXBIO said that the agency has already recommended a randomized controlled trial but suggested that external controls could be used for demonstrating substantial evidence of effectiveness if the effect size is great enough.
The biotech believes the data released today has met that bar—but Leerink is not so sure. The correlation data is a “clear positive,” but will require some leeway from an agency that has not entirely shown flexibility in recent months.
REGENXBIO Chief Medical Officer Steve Pakola said that correlation of microdystrophin expression and functional improvements has never been demonstrated before, calling the achievement a “landmark distinction” among DMD gene therapies. The only other is Sarepta’s Elevidys, which has been challenged by safety concerns since its 2023 approval.
Beyond the gene therapy results, REGENXBIO said the FDA has lifted a clinical hold that was placed on the Hurler syndrome gene therapy RGX-111 in January, according to CEO Curran Simpson.
The company has also appealed the rejection of RGX-121, a gene therapy in development for the ultrarare neurodegenerative disease mucopolysaccharidosis II, also known as Hunter syndrome. In the complete response letter, the FDA raised concerns about eligibility criteria and the natural history external control used in the Phase 1/2/3 RGX-121-101 study, along with the appropriateness of the surrogate endpoint.
The agency will have to now weigh similar issues with RGX-202.
