Dive Brief:

• An experimental gene therapy from Lexeo Therapeutics reduced signs of heart complications in a small clinical trial of people with the rare disease Friedreich’s ataxia, the company said Monday. 
• Interim results from an early-stage trial showed that among six people who had enlarged hearts at the study’s start, four saw an average 11% reduction in the size of their left ventricles a year after treatment with Lexeo’s therapy. Two had a mean 18% reduction after 18 months. Lexeo said other markers of heart damage also declined, and that biopsies showed an increase in the protein, frataxin, the therapy is designed to produce. 
• There were no serious adverse events, study discontinuations or signs of an immune response to the treatment, according to Lexeo. The company will test a higher dose level and present further results at a medical meeting later this year. In the meantime, the company intends to “explore expedited development” of the therapy, including the “potential for accelerated approval,” said Eric Adler, Lexeo’s head of research and chief medical officer, in a statement. 

Dive Insight:

Friedreich’s ataxia is known as a neurodegenerative disorder, as the progressive nerve damage it causes affects a person’s coordination and ability to walk or speak. But the most common reason people die from the condition is a type of cardiomyopathy that can lead to heart failure. 

The only drug available for Friedrich’s ataxia, Biogen’s Skyclarys, slows neurological disease progression but doesn’t impact the heart. Lexeo’s therapy is different, designed to deliver, inside an engineered virus, instructions for a protein that restores mitochondrial function in heart cells.

The company says this approach could yield the first therapeutic option for the estimated 5,000 people in the U.S. with Friedreich’s ataxia cardiomyopathy. Lexeo executives are also suggesting the results so far make a compelling case for a Food and Drug Administration division whose leader, Peter Marks, has shown a desire to use “accelerated” approvals to more quickly clear gene-based treatments for rare conditions. 

The agency granted a speedy approval to a Duchenne muscular dystrophy gene therapy last year and converted that OK to a broad clearance in June despite mixed study results. The FDA also indicated it may be open to granting an accelerated approval to Rocket Pharmaceuticals if the company’s therapy for Danon disease, a genetic heart condition, displays a meaningful effect on left ventricle size and protein expression. 

On a Monday conference call with analysts, executives declined to say whether it’s spoken with the FDA. CEO Nolan Townsend only said the company will “comment on the regulatory picture in a future update.” But Townsend pointed to recent “increased regulatory flexibility” as a reason the company is optimistic, citing the agency’s willingness to grant accelerated approvals as well as the data requirements that supported the 2022 clearance of Bristol Myers Squibb’s cardiomyopathy drug Camzyos.

There is “regulatory precedent” showing a reduction in left ventricle size as a surrogate for a clinical benefit in multiple other diseases, said Lexeo CMO Adler, on the call. In a May survey of heart specialists, Paul Matteis, an analyst at the investment bank Stifel, found that a 10% reduction — a mark hit by half of the study participants after a year — was a “clinically meaningful” threshold for significance. 

But there are questions too, among them how strong the effects will be at higher doses, how long they’ll last and the requirements for approval. For example, Matteis noted that it’s unclear whether left ventricle size is the “right” study goal in Friedreich’s ataxia given baseline levels vary between patients. Lexeo also couldn’t prove that participants’ function improved after treatment. Company shares fell as much as 30% in early trading.

Still, “we have increased confidence that there's a real clinical signal here,” Matteis wrote in a note to investors on Monday.