Lexeo Therapeutics gave the 5,000 Americans with Friedreich’s ataxia cardiomyopathy reason for optimism, publishing early results that suggest its LX2006 gene therapy could be able to treat FA cardiomyopathy.
- Friedreich’s ataxia (FA) is a neurodegenerative disorder caused by loss of function mutations in the frataxin gene, although FA patients generally die from FA cardiomyopathy.
- FA is currently only treated by Biogen’s Skyclarys, which slows neurological symptom progression, but doesn’t treat FA cardiomyopathy.
- LX2006 is designed to promote frataxin protein expression and restore mitochondrial function in myocardial cells, potentially treating FA cardiomyopathy.
The analysis combined data from Lexeo’s SUNRISE-FA Phase 1/2 clinical trial and a Weill Cornell Phase 1A trial that were designed to evaluate whether LX2006 could improve FA-related cardiac dysfunction.
Based on interim 6-to-18-month data from eight participants, LX2006 led to improvements to…
- Left ventricular mass index – Of the participants with elevated LVMI at baseline (n=6), four achieved 11.4% average LVMI reductions at 12 months, while two showed 18.3% average reductions at 18 months.
- Left ventricular lateral wall thickness – Participants with LV wall thickening (n=6) achieved a 13.6% average wall thickness reduction at 12 months.
- High-sensitivity Troponin I levels – Participants with elevated hsTnI (n=5) achieved a 53.3% average reduction at 12 months.
- Frataxin levels – All tested patients (n=5) showed increased frataxin levels in their myocardial biopsies following treatment.
LX2006 was also well tolerated in both studies, with no treatment-related serious adverse events and no discontinuations.
- However, LX2006 might have a limited impact on cardiorespiratory fitness, improving participants’ V02 max levels by just 1% at 12 months and 4% after 12 months.
Lexeo will now advance LX2006 to its third dose cohort, with company execs suggesting that a “higher dose cohort could achieve higher protein levels,” and stating that LX2006 could achieve an accelerated approval due to the lack of FA cardiomyopathy treatments.
- They do have a point: the FDA has recently shown support for other gene-based treatments of rare conditions and LX2006 gained FDA Fast Track Designation in April.
However, even with this evidence and precedent, a Wall Street sell-off drove a 36% drop in Lexeo’s stock price since last Friday, due to the limited cardiorespiratory evidence and what some people view as another case of Wall Street “selling on the news.”
The Takeaway
Although Lexeo still has plenty to prove (scientifically and financially), these results suggest that the first Friedreich’s ataxia cardiomyopathy treatment might be on the horizon.
