Alnylam Hits Milestone in Heart Study of RNAi Therapy Vutrisiran

Alnylam Pharmaceuticals is advancing rapidly in its efforts to secure new marketing approvals for vutrisiran, following positive results from a Phase III study. This RNAi therapeutic has shown promise in treating ATTR amyloidosis with cardiomyopathy (ATTR-CM), meeting both primary and secondary endpoints. The company revealed these findings on Monday, leading to a 39% increase in its stock during premarket trading.

The top-line data from the study indicated that vutrisiran reduced the composite of all-cause mortality and recurrent cardiovascular events by 28% compared to a placebo. This reduction was even more significant in patients who were not on Pfizer's ATTR-CM drug Vyndamax (tafamidis) at the start, showing a 33% decrease. CEO Yvonne Greenstreet commented on the data, stating, "We really feel that this data has set the bar for a new standard of care."

Vutrisiran, marketed under the name Amvuttra, had already received FDA approval in 2022 for treating nerve damage in adults with hereditary ATTR amyloidosis, achieving sales of $558 million last year. Greenstreet emphasized the potential for vutrisiran to drive significant revenue growth, describing the latest results as a crucial moment for the company. Alnylam plans to use a priority review voucher to expedite the FDA filing process.

The HELIOS-B study involved 655 adults with ATTR-CM, who were randomized to receive either vutrisiran or a placebo subcutaneously every three months. The trial assessed the RNAi therapy's impact on reducing all-cause mortality and recurrent cardiovascular events, both in the overall population and among the 60% of patients not taking Vyndamax at baseline.

In addition to the primary endpoint results, vutrisiran reduced all-cause mortality by 36% in the overall population, and by 35% in those not on Vyndamax at baseline. The drug also showed significant clinical benefits on measures such as the 6-minute walk test (6-MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ), and New York Heart Association (NYHA) Class at the 30-month mark.

Regarding safety, Alnylam reported that vutrisiran's profile was "encouraging" in the HELIOS-B study. The rates of adverse events (AEs), serious AEs, and discontinuations due to AEs were comparable between the vutrisiran and placebo groups. The detailed results have been submitted as a late-breaking abstract for presentation at the European Society of Cardiology (ESC).

Earlier this year, investors experienced some concern when Alnylam announced changes to the statistical plan for HELIOS-B. These changes included extending the minimum follow-up period and adjusting the primary endpoint to encompass assessments in both the overall population and those not on Vyndamax at baseline. Despite initial worries that these changes might signal a lack of confidence in the study, Alnylam's chief medical officer Pushkal Garg clarified that the adjustments were intended "to optimize the study for success, and a strong and competitive label."