Myqorzo Expands to Non-Obstructive Hypertrophic Cardiomyopathy

Cytokinetics (CYTK)'s Myqorzo (aficamten), an oral therapy that inhibits cardiac myosin, was approved by the FDA on December 19, 2025, for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM). In the ACACIA-HCM Phase 3 trial, 517 patients with non-obstructive HCM showed a 11.4-point improvement in KCCQ-CSS at week 36, which was 3.0 points higher than the 8.4-point improvement in the placebo group. The pVO2 difference was 0.67 mL/kg/min. The p-values for both co-primary endpoints were 0.021 and 0.003, meeting pre-specified criteria and establishing a foundation for entry into the non-obstructive HCM market, where direct disease-targeting therapies have been lacking.

Safety Concerns Over Heart Failure Outweigh Efficacy

In the Myqorzo group, 10.5% of patients had left ventricular ejection fraction (LVEF) below 50%, compared to 0.8% in the placebo group. Major heart failure events not associated with LVEF decline were observed in 10 patients versus 3 in the placebo group. However, no deaths occurred in the Myqorzo group, while 3 deaths were recorded in the placebo group. Heart failure events primarily occurred before week 12, the dose titration period, and responded to diuretic therapy. Given the FDA's current oHCM approval includes boxed warnings, echocardiographic monitoring, and a Risk Evaluation and Mitigation Strategy (REMS), safety management will be a key review focus for the non-obstructive HCM supplemental New Drug Application (sNDA) expected in Q4 2026. Bristol Myers Squibb (BMY)'s Camzyos (mavacamten), another cardiac myosin inhibitor, is only approved for oHCM as of April 28, 2022.

Redemplo Leads in Severe Hypertriglyceridemia Competition

Arrowhead Pharmaceuticals (ARWR)'s Redemplo (plozasiran), an siRNA therapy that inhibits hepatic apolipoprotein C-III (APOC3), is already marketed in the U.S. and Europe for familial chylomicronemia syndrome (FCS). In the SHASTA-3 and SHASTA-4 Phase 3 trials involving 757 patients with severe hypertriglyceridemia (sHTG), triglyceride levels decreased by 79% and 81%, respectively, over 12 months. The integrated analysis showed a 78% reduction in acute pancreatitis incidence compared to placebo. The company plans to submit an sNDA to the FDA by late 2026, with analysts projecting a $6 billion market size by 2035 and a 60% estimated market share. The direct competitor is Ionis Pharmaceuticals (IONS)'s Tryngolza (olezarsen), an APOC3-targeting antisense oligonucleotide, which received FDA approval on June 24, 2026, for sHTG and acute pancreatitis risk reduction.

Wainua's Failure Disrupts Treatment Sequence for ATTR-CM

AstraZeneca (AZN) and Ionis' Wainua (eplontersen), a GalNAc-conjugated antisense therapy that inhibits TTR protein production, was approved by the FDA on December 21, 2023, for hereditary ATTR polyneuropathy but failed in ATTR cardiomyopathy (ATTR-CM). In the CARDIO-TTRansform Phase 3 trial with 1,432 patients, the hazard ratio for cardiovascular death and recurrent cardiovascular events at 140 weeks was 0.89 (95% CI 0.73–1.09, p=0.277), which was not statistically significant. Patients using baseline TTR stabilizers did not show additional benefit. This outcome challenges the clinical efficacy of Alnylam Pharmaceuticals (ALNY)'s RNAi therapy Amvuttra (vutrisiran) and late-stage candidate nucresiran, while reinforcing the treatment sequence of TTR stabilizers such as Pfizer (PFE)'s Vyndamax (tafamidis) and BridgeBio Pharma (BBIO)'s Attruby (acoramidis).