Lexeo Therapeutics, FDA Feedback Opens Faster Path, Pivotal Study for Friedreich Ataxia Gene Therapy Could Shrink and Speed Up Approval

Author: Benzinga Newsdesk | October 07, 2025 05:04am

Lexeo Therapeutics, Inc. (NASDAQ:LXEO), a clinical stage genetic medicine company dedicated to pioneering novel treatments for cardiovascular diseases, today announced updates to key components of an Accelerated Approval pathway for LX2006 in Friedreich ataxia (FA) cardiomyopathy, alongside new interim clinical data from ongoing Phase I/II studies.

"We are encouraged by our recent dialogue with the FDA on LX2006, and we appreciate the Agency's collaborative spirit as we work to deliver a potentially life-changing therapy to the FA community as efficiently as possible," said R. Nolan Townsend, Chief Executive Officer of Lexeo Therapeutics. "Given the highly compelling data to date that demonstrate clinically meaningful improvements across both cardiac and neurologic measures of FA, we are now pursuing a development strategy that could enable a smaller pivotal study, given the potential to pool data with the ongoing Phase I/II trials, as well as potentially assessing the co-primary endpoint of LVMI earlier than 12 months. This approach could accelerate our overall timeline toward a BLA submission for LX2006 under the Accelerated Approval pathway."

FDA Feedback to Date

In response to questions from the Company regarding the possibility of a faster path to a BLA, the FDA has indicated openness to a BLA submission for accelerated approval that includes clinical data from the ongoing Phase I/II studies of LX2006 pooled with new clinical data to be generated in the planned pivotal study. To enable pooling of these data to support licensure, Lexeo will submit enhanced manufacturing comparability data and meet an additional nonclinical requirement prior to the initiation of the planned pivotal study, given the Company's intention to leverage its optimized, high-yield Sf9-baculovirus manufacturing platform for future clinical and commercial drug supply, compared to the adherent HEK293 process used for Phase I/II clinical supply. The FDA also previously agreed to evaluate the co-primary endpoint of LVMI at a time point earlier than 12 months. Lexeo continues to engage with the FDA on the pivotal protocol and comparability. In discussions to date, there have been no changes to the previously disclosed alignment with the FDA on key parameters related to the LX2006 planned registrational study.

Collectively, Lexeo believes this regulatory feedback has the potential to reduce the size and length of the planned pivotal study, possibly accelerating the overall timeline to BLA submission. Lexeo plans to initiate the LX2006 pivotal study as soon as possible in the first half of 2026, pending finalization of the trial protocol. FDA has previously granted Breakthrough Therapy, Regenerative Medicine Advanced Therapy (RMAT), Orphan Drug and Fast Track designations to LX2006, and admitted LX2006 into the CMC Development and Readiness Pilot (CDRP) program.

LX2006 Interim Clinical Update (n=16 participants with >6-months of follow-up)

Updated interim clinical data from both ongoing Phase I/II studies of LX2006 continue to show encouraging safety and efficacy, exceeding the thresholds previously agreed with FDA for co-primary endpoints LVMI and frataxin expression.

Left ventricular mass index (LVMI):

• Among participants with abnormal baseline LVMI (key inclusion criteria for pivotal study; n=6):
  • 6 of 6 participants achieved LVMI measurements within the normal range as of latest visit
  • 5 of 6 participants achieved >10% improvement by 12 months
  • 18% mean improvement in LVMI at 6 months and 23% mean improvement at 12 months, exceeding 10% FDA-aligned threshold for pivotal study
  • 28% mean improvement in LVMI at 6 months and 33% mean improvement at 12 months in mid- and high-dose cohorts (n=3), suggesting dose-dependent improvement
• Among participants with normal baseline LVMI (n=10), the majority demonstrated LVMI improvement or stabilization over time

Secondary cardiac biomarkers:

• 14 of 16 participants achieved >25% reduction in high-sensitivity troponin I from baseline at latest visit
• 14 of 16 participants achieved reduction or stabilization in lateral wall thickness (LWT) from baseline at latest visit

Modified Friedreich Ataxia Rating Scale (mFARS):

• 2.0-point mean improvement from baseline at latest visit across all participants with >6-months of follow-up (n=16)
• 11 of 16 participants achieved reduction or stabilization in mFARS from baseline at latest visit

Previously reported data from Lexeo's ongoing SUNRISE-FA trial (n=8) showed that all study participants achieved increases in frataxin protein expression from baseline at 3 months, with dose-dependent increases observed across cohorts.

LX2006 Interim Safety Update (n=17 participants)

• Treatment with LX2006 has been generally well tolerated with no Grade 3+ SAEs to date
• No clinically significant complement activation
• Minimal, transient liver function test (LFT) elevations
• No signs of frataxin over-expression observed in cardiac tissue
• No participants discontinued from either study
• One previously disclosed, possibly treatment-related Grade 2 event of asymptomatic myocarditis observed one year after dosing

Posted In: LXEO