Novartis and Ionis Lp(a) Drug Pelacarsen Fails Late-Stage Cardiovascular Trial

The U.S. Food and Drug Administration has approved an expanded indication for Bristol Myers Squibb's CAMZYOS (mavacamten) to treat symptomatic obstructive hypertrophic cardiomyopathy in adults and pediatric patients weighing 30 kg (66 lbs) or more, making it the only FDA-approved therapy for oHCM in a pediatric population and giving it the broadest indication of any cardiac myosin inhibitor. The approval is based on positive results from the Phase 3 SCOUT-HCM trial, which evaluated CAMZYOS (n=23) versus placebo (n=21) in patients aged 12 to under 18 years with symptomatic NYHA Class II-III oHCM. CAMZYOS met the trial's primary endpoint, showing a statistically significant reduction in Valsalva left ventricular outflow tract gradient at Week 28 compared with placebo, with a least-squares mean difference from placebo of minus 48.0 mm Hg (95% CI, minus 67.7 to minus 28.3; P<0.0001). No patients in SCOUT-HCM experienced left ventricular ejection fraction below 50%, no adverse events led to treatment discontinuation, and no new adverse reactions were identified beyond the safety profile observed in adults. CAMZYOS was first approved by the FDA in 2022 for adults with symptomatic NYHA class II-III oHCM and has been prescribed by more than 5,000 healthcare providers to over 25,000 patients in the U.S. alone; the pediatric data is now being discussed with multiple global regulatory authorities for potential pediatric indications.

Cantor Fitzgerald initiated coverage of Lexicon Pharmaceuticals at overweight, citing optimism over upcoming phase 3 data for the SGLT1/2 inhibitor Inpefa, also known as sotagliflozin, as a treatment for hypertrophic cardiomyopathy, with results expected in the first quarter of 2027. The firm set a price target of $8, which it said represents roughly 344% upside based on the September 27 close. Analyst Steve Seedhouse wrote that Inpefa is completely orthogonal to cardiac myosin inhibitors, where most of the recent innovation in HCM has come from, so it will complement rather than compete with those drugs, examples of which include Bristol Myers Squibb's Camzyos, or mavacamten, and Cytokinetics' Myqorto, or aficamten. Seedhouse added that background cardiac myosin inhibitors are allowed in the phase 3 study SONATA-HCM, so if SONATA-HCM works, sotagliflozin is essentially unencumbered competitively in a proven blockbuster market. He noted several potential ways SGLT and SGLT2 are involved in HCM, including reducing epicardial adipose tissue and mitochondrial oxidative stress and restoring glucose levels and ATP homeostasis. Inpefa is already approved to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure in adults with heart failure, or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors.