A recent article at BioPharma Dive outlines the findings of a study into Lexeo’s experimental gene therapy. The six participants in the recently conducted interim trial had enlarged hearts associated with Friedrich’s ataxia. One year after treatment, four people out of the six who were enrolled in the trial saw an average 11% reduction in their left ventricles due to Lexeo’s therapy, and two people were reported as having 18% reduction 18 months after the onset of the trial.
According to the company, other markers of heart damage declined while biopsies indicated an increase in the frataxin protein for which the therapy was created. Lexeo said that there were no significant adverse events or any immune response from the treatment. Eric Adler, who is head of Lexeo’s research department, issued a statement indicating that the research team will test a higher dose and report its results at this year’s upcoming medical meeting. He also noted that Lexeo will move ahead in exploring further development of the therapy which includes the potential of accelerated approval.
What is Friedreich’s Ataxia?
The disease is a neurodegenerative disorder causing progressive damage to nerves. It affects a person’s coordination, which in turn creates an inability to speak or walk. However, the disease becomes fatal when it affects the heart, causing cardiomyopathy. Currently, the only available drug for the disease is Biogen’s Skyclarys which, although it slows neurological progression of the disease, does not benefit the heart. Lexeo’s therapy has been designed to deliver its payload, which consists of an engineered virus with instructions to make a protein that restores mitochondrial functioning in the heart’s cells. Over 5,000 people in the United States have been diagnosed with Friedreich’s ataxia cardiomyopathy. Lexio executives point to trial results that make a compelling case for following the lead of Peter Marks, FDA administrator, who indicated a strong desire to accelerate approvals.
About Accelerated Approval
The FDA instituted the Accelerated Approval program to facilitate approval of drugs that treat serious conditions and thereby fill unmet needs. The decision is based on a “marker” such as a laboratory measurement, physical sign or other that can predict a clinical benefit. The process shortens the time prior to FDA approval. Lexeo used the example of the mixed review of a Duchenne muscular dystrophy gene therapy a year ago. The FDA granted an accelerated approval and broad clearance in June 2023 despite the mixed reviews.
The company referenced its therapy for Danon disease which is a genetic heart condition claiming that the results merit supporting the potential for accelerated approval in treatment for individuals who have heart complications due to Friedreich’s ataxia.
The FDA has developed four distinct and successful approaches to making such drugs available as rapidly as possible:
• Priority Review
• Breakthrough Therapy
• Accelerated Approval
• Fast Track
These approaches have one common advantage: speed. Therefore, there is often confusion about the specific meaning of each designation. For instance, a Priority Review designation references the FDA’s goal to act on an application within 6 months. An example of an accelerated approval was the Agency’s nod to a Duchene muscular dystrophy gene therapy that received broad clearance despite mixed study results. The FDA said that it may be open to Rocket Pharmaceuticals receiving an accelerated approval if the company’s therapy, Danon that treats genetic heart conditions, displays a significant effect on the size of the left ventricle and demonstrates protein expression.
Lexeo CEO Nolan Townsend referenced increased regulatory flexibility as a reason to be optimistic. In addition, he referenced a regulatory precedent that showed a reduction in the size of the left ventricle as a clinical benefit in other diseases. In May of 2023, analyst Paul Matteis termed as clinically meaningful the 10% reduction that was reached within one year by half of the study’s participants.
And Now the Questions
• If the doses are raised how strong will they be?
• How long will they last?
• What are the requirements for approval since baseline levels vary for every patient?
• Additionally, the company must give proof to back up the claim of improved function after treatment.
