Lexeo gene therapy shows heart benefit in small study

Lexeo Therapeutics announced that its experimental gene therapy has shown promising results in a small clinical trial for Friedreich's ataxia, a rare disease that often leads to heart complications. In an early-stage study involving patients with enlarged hearts, the therapy reduced the size of the left ventricle by an average of 11% after one year in four out of six participants. Two of these participants saw an 18% reduction after 18 months. The treatment also led to a decrease in other markers of heart damage and an increase in the protein frataxin, which the therapy aims to produce.

Notably, there were no serious adverse events, study discontinuations, or signs of immune response to the treatment. Lexeo plans to test a higher dose level and present further results at a medical meeting later this year. The company is also considering expedited development of the therapy, including the potential for accelerated approval, according to Eric Adler, Lexeo's head of research and chief medical officer.

Friedreich's ataxia is primarily recognized as a neurodegenerative disorder, affecting coordination, speech, and mobility. However, the most common cause of death in these patients is cardiomyopathy, which can lead to heart failure. Currently, the only drug available, Biogen's Skyclarys, slows neurological progression but does not affect the heart.

Lexeo’s approach is unique. The company has developed a therapy that delivers genetic instructions for producing a protein that restores mitochondrial function in heart cells. This method could provide the first therapeutic option for the estimated 5,000 people in the U.S. with Friedreich's ataxia cardiomyopathy. Lexeo executives believe the initial results support a compelling case for the Food and Drug Administration’s accelerated approval process, which aims to expedite the clearance of gene-based treatments for rare conditions.

The FDA has previously granted accelerated approval for a Duchenne muscular dystrophy gene therapy and has shown openness to granting similar approvals for treatments targeting genetic heart conditions like Danon disease. Although Lexeo did not specify whether it has engaged with the FDA, CEO Nolan Townsend indicated that the company is optimistic about its regulatory prospects, citing increased regulatory flexibility and the FDA’s willingness to grant accelerated approvals.

During a recent call, Lexeo’s Chief Medical Officer, Eric Adler, highlighted a regulatory precedent showing that a reduction in left ventricle size can be a surrogate marker for clinical benefit in various diseases. An investment bank analyst, Paul Matteis, found in a survey of heart specialists that a 10% reduction in left ventricle size—a threshold met by half of the study participants after one year—was considered clinically significant.

However, questions remain about the therapy’s long-term effects, the strength of its impact at higher doses, and the specific requirements for regulatory approval. For instance, it's unclear whether left ventricle size is the most appropriate endpoint for studies in Friedreich’s ataxia, given baseline levels can vary among patients. Additionally, Lexeo has yet to prove that the therapy improves participants' overall function. Company shares experienced a 30% drop in early trading following the announcement.

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