Alnylam unveils positive Phase III results for rare heart disease drug vutrisiran

Alnylam Pharmaceuticals recently saw its stock surge by 32% following the announcement of encouraging topline results from a late-stage study of its RNA interference (RNAi) therapeutic, vutrisiran, aimed at treating ATTR amyloidosis with cardiomyopathy (ATTR-CM).

On June 24, the company revealed that the Phase III HELIOS-B study (NCT04153149) successfully met its primary goal by showing statistically significant reductions in the composite of all-cause mortality and recurrent cardiovascular events. This achievement was observed across both the monotherapy and overall study populations. Specifically, patients receiving vutrisiran as monotherapy experienced a 33% reduction in the composite endpoint, with a hazard ratio (HR) of 0.672. For the overall population, there was a 28% reduction, with an HR of 0.718.

In addition to the primary endpoint, vutrisiran also demonstrated considerable improvements across all secondary endpoints. These included assessments of disease progression via the 6-minute walk test (6MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ), and New York Heart Association (NYHA) Class, all evaluated at the 30-month mark. The study also found a reduction in all-cause mortality measured up to 42 months, showing decreases of 35% and 36% in the monotherapy and overall populations, respectively.

The HELIOS-B study was a multi-center, double-blind, parallel assignment trial involving 655 adult patients who were randomized into experimental treatment and placebo groups in a 1:1 ratio. Participants in the experimental group received 25mg subcutaneous vutrisiran at three-month intervals over a 36-month period. The randomization process took into account the patients’ initial use of Pfizer’s Vyndaqel/Vyndamax (tafamidis), an existing approved treatment for ATTR, as well as the specific type of ATTR disease, NYHA Class I or II, and the patients' age.

Vutrisiran exhibited consistent effects across key patient subgroups, including those on baseline Vyndaqel or Vyndamax. CEO Yvonne Greenstreet, MBChB, stated in a press release that Alnylam's treatment has the potential to become the new standard of care for ATTR-CM. Currently, Vyndamax or Vyndaqel is the most commonly used treatment for patients with ATTR-CM, and Pfizer’s medication was recently introduced by the National Health Service (NHS) for treating ATTR-CM in the UK.

According to forecasts by GlobalData, Vyndamax/Vyndaqel is expected to generate total sales of $5.6 billion by 2026, while vutrisiran is projected to achieve global sales of $3.6 billion by 2030.

As the study results indicate a significant improvement in cardiovascular outcomes for patients treated with vutrisiran, Alnylam is preparing to file the data with regulatory authorities to expedite the treatment's market entry. Dr. Pushkal Garg, Alnylam's Chief Medical Officer, emphasized the company's urgency in moving forward. The plan includes initiating submissions to global regulatory agencies in 2024, with a New Drug Application (NDA) and a Priority Review Voucher to be filed with the U.S. Food and Drug Administration (FDA) later in the year.