Top Drug Development Readouts to Watch

Aficamten Achieves First Phase 3 Success in Non-Obstructive HCM

Cytokinetics reported that aficamten met its primary endpoint in the phase 3 ACACIA-HCM trial, improving the Kansas City Cardiomyopathy Questionnaire (KCCQ) score by 11.4 points after 36 weeks among 517 patients, compared with an 8.4-point gain for placebo, according to ESC presentation data. Peak oxygen uptake increased by 0.64 mL/kg/min with aficamten and remained essentially unchanged with placebo. The drug works by reducing excessive contraction of the heart muscle, addressing a form of the disease that previously lacked targeted therapy after Bristol Myers Squibb’s mavacamten missed its primary endpoint in the ODYSSEY-HCM trial.

The benefit carried a trade-off in cardiac function. Left ventricular ejection fraction fell below 50% in 10.5% of patients receiving aficamten compared to 0.8% on placebo, though these reductions proved reversible. Cytokinetics plans to file for an expanded U.S. approval in the fourth quarter of 2026. Meanwhile, Edgewise Therapeutics presented 12-week phase 2 data for EDG-7500, a cardiac sarcomere modulator that demonstrated biomarker and symptom improvements while aiming to preserve systolic function.

Plozasiran Cuts Triglycerides and Pancreatitis in Phase 3 Trials

Arrowhead Pharmaceuticals demonstrated clear RNAi success with plozasiran in the SHASTA-3 and SHASTA-4 trials, where 757 patients received the drug or placebo once every three months. According to ESC data, median triglyceride levels fell by 79% and 81% after one year, and more than 90% of treated patients brought their triglycerides below the 500 mg/dL severe hypertriglyceridemia threshold. Plozasiran targets APOC3, a liver-produced protein that slows triglyceride clearance.

The RNAi therapy reduced the rate of acute pancreatitis events by 78% overall compared with placebo, yielding a 4.1% risk reduction over one year, and achieved a 91% reduction in patients with a previous history of pancreatitis. Worsening glycemic control occurred in 14.3% of treated patients versus 8.7% on placebo. Arrowhead plans to file for U.S. approval in severe hypertriglyceridemia before the end of 2026. Advancing even less frequent dosing, Ionis presented phase 1 data for ION775, showing a single dose reduced triglycerides by up to 68.4% at six months in a 40-participant study.

CRISPR Therapeutics Reports Durable Lipid Lowering with CTX310

CRISPR Therapeutics presented one-year durability data from a phase 1a study of CTX310, an in vivo CRISPR-Cas9 therapy targeting ANGPTL3 to permanently reduce triglycerides and LDL cholesterol. Fifteen participants with difficult-to-control high cholesterol or triglycerides received a single intravenous dose on top of existing treatment. At the highest dose, circulating ANGPTL3 fell by an average of 79%, triglycerides dropped by 48%, and LDL cholesterol decreased by 53%, with no treatment-related serious adverse events reported. CRISPR Therapeutics has advanced CTX310 into a phase 1b trial focusing on severe hypertriglyceridemia and refractory hypercholesterolemia.

Medera Revisits Cardiac Gene Therapy in HFpEF with SRD-002

Medera presented 12-month data from a first-in-human study of SRD-002, a one-time gene therapy utilizing an AAV1 vector to deliver an additional SERCA2a gene copy to improve heart relaxation in heart failure with preserved ejection fraction (HFpEF). Among ten patients split evenly across lower and higher dose cohorts, eight met a prespecified threshold for normalization of cardiac filling pressure at 12 months, and average pulmonary capillary wedge pressure during peak exercise fell by roughly 30%. Average KCCQ scores increased by 17.8 points, and five of six patients with NYHA class 3 symptoms improved to class 2. Medera plans to advance SRD-002 into a randomized phase 2b study.

Eplontersen Suppresses Target Without Reducing Clinical Events in ATTR-CM

AstraZeneca and Ionis presented full phase 3 results from the CARDIO-TTRansform trial involving over 1,400 patients with transthyretin amyloid cardiomyopathy (ATTR-CM) treated for up to 140 weeks. While eplontersen successfully suppressed circulating TTR, it failed to reduce cardiovascular events or deaths. The composite primary endpoint of cardiovascular deaths and recurrent cardiovascular events occurred in 381 patients in the eplontersen group and 392 with placebo, while cardiovascular deaths reached 74 and 70, respectively. Patients on eplontersen experienced slower declines in physical function, including a 27.5-meter drop in six-minute walking distance compared to 47.3 meters on placebo. Among patients not taking a TTR stabilizer at baseline, eplontersen was associated with a 29% lower rate of the primary endpoint, whereas patients already taking a stabilizer showed no evidence of benefit.

Milvexian Fails to Reduce Cardiovascular Events in Acute Coronary Syndrome

Novartis Highlights Sustained Inflammation Reduction with Pacibekitug

Subsequent evaluations from upcoming clinical investigations will clarify if the early signals observed during ESC presentations eventually translate into tangible therapeutic advantages.

AstraZeneca Advances Oral Relaxin Agonist AZD5462 in Phase 2b LUMINARA

In a primary phase III Latitude Atlas analysis for moderate-to-severe plaque psoriasis, Takeda’s TAK-279 (zasocitinib) outperformed Bristol Myers Squibb’s Sotyktu (deucravacitinib). The re

Frequently Asked Questions

What is aficamten and how does it work in HCM?

Aficamten is a cardiac myosin inhibitor developed by Cytokinetics. It reduces excessive contraction of the heart muscle and achieved positive phase 3 results in non-obstructive hypertrophic cardiomyopathy by improving exercise capacity and KCCQ symptom scores.

Why did eplontersen fail its primary endpoint in ATTR-CM?

According to the CARDIO-TTRansform trial results presented at ESC, eplontersen successfully suppressed its intended target and lowered circulating TTR levels, but this target suppression did not translate into a statistically significant reduction in cardiovascular events or deaths compared with placebo.

What did the LIBREXIA-ACS trial show regarding milvexian?