FDA Grants Fast and Orphan Drug Designations for Lexeo’s Gene Therapy Candidate for Arrhythmogenic Cardiomyopathy

Rare Daily Staff

The U.S. Food and Drug Administration has granted Fast Track and Orphan Drug designations to Lexeo Therapeutics’ LX2020, the company’s gene therapy candidate designed to intravenously deliver a functional PKP2 gene to cardiac muscle for the treatment of arrhythmogenic cardiomyopathy caused by mutations in the PKP2 gene.

“Receiving both Orphan Drug and Fast Track designations from the FDA for LX2020 further validates the importance of progressing a potential one-time treatment option for patients suffering from PKP2-ACM,” said R. Nolan Townsend, CEO of Lexeo Therapeutics. “PKP2-ACM is one of the most prevalent diseases in the genetic cardiovascular space and with no approved therapeutic options, we look forward to the possibility of delivering a first and best in class treatment option for patients.”

LX2020 is an AAVrh10-based gene therapy candidate designed to intravenously deliver a functional PKP2 gene to cardiac muscle for the treatment of arrhythmogenic cardiomyopathy caused by mutations in the PKP2 gene (PKP2-ACM). PKP2 mutations are associated with approximately 75 percent of all genetic cases of ACM, estimated to affect approximately 60,000 patients in the United States. PKP2 mutations can cause fibro-fatty replacement of heart muscle and severe abnormal heart rhythms, or arrhythmias, that cause cardiac dysfunction and can result in sudden cardiac death. Currently there are no approved treatments to slow, prevent or reverse disease progression in patients with PKP2-ACM. LX2020 is designed to increase desmosomal PKP2 protein levels, reassemble desmosomes and restore myocardial cell function.

The planned phase 1/2 trial, HEROIC-PKP2, is a first in human, 52-week open-label, dose-escalating, multicenter trial to determine the safety and tolerability of LX2020 in adult patients with PKP2-ACM. Preliminary efficacy measures will evaluate myocardial protein expression, biomarkers measuring cardiac structure and function, and arrhythmia burden. LX2020 will be administered as a one-time intravenous infusion to patients in two ascending-dose cohorts, evaluating the 2.0×1013 vg/kg and 6.0×1013 vg/kg dose levels with three patients in each cohort, and the potential for cohort expansion. Long-term safety and efficacy will be evaluated for an additional four years following completion of the initial trial.

The FDA grants Orphan Drug designation status to support the development of medicines for rare disorders that affect fewer than 200,000 people in the U.S. Orphan Drug designation provides certain benefits, such as market exclusivity upon regulatory approval, exemption of FDA application fees, as well as tax credits for qualified clinical trials. Fast Track designation allows more frequent FDA interactions to facilitate development and expedite the review process for novel drug candidates that treat serious or life-threatening diseases and address unmet medical needs.

Photo: R. Nolan Townsend, CEO of Lexeo Therapeutics