Alnylam Succeeds in Phase III Cardio Trial, Seeks RNAi Therapy Label Expansion

Alnylam Pharmaceuticals has announced promising results from its Phase III HELIOS-B study, which investigates the efficacy of their RNA interference (RNAi) therapy, Amvuttra (vutrisiran), in patients with transthyretin amyloidosis and cardiomyopathy (ATTR-CM). According to the data, Amvuttra significantly reduces the risk of death and recurrent cardiovascular events in these patients.

Pushkal Garg, the Chief Medical Officer of Alnylam, expressed the company’s excitement over the overwhelmingly positive outcomes of the HELIOS-B study, highlighting the potential of Amvuttra as a robust treatment option for ATTR-CM patients. Garg mentioned that the therapy not only improved cardiovascular outcomes but also enhanced survival rates and quality of life for the patients involved in the study.

Alnylam is expediting the regulatory submission process for Amvuttra, aiming to file a supplemental New Drug Application with the U.S. Food and Drug Administration (FDA) and other global regulatory bodies later this year. The company has also submitted the study data as a late-breaking abstract to the European Society of Cardiology for presentation at their forthcoming medical conference.

The HELIOS-B study is a randomized, double-blinded, placebo-controlled trial that included 655 patients diagnosed with ATTR-CM. Throughout a double-blind period of up to 36 months, participants received either a 25-mg subcutaneous dose of Amvuttra or a placebo every three months. Following this period, eligible patients were allowed to continue receiving Amvuttra in an open-label extension phase.

At the start of the study, some patients were also receiving Pfizer’s Vyndamax (tafamidis), an FDA-approved oral medication for ATTR-CM. In these patients, Amvuttra decreased the risk of all-cause mortality and recurrent cardiovascular events by 28%. For patients treated solely with Amvuttra, the reduction in risk for the composite endpoint was 33%.

In addition to the primary outcomes, Amvuttra excelled in several key secondary endpoints. Patients who had been exposed to Vyndamax at baseline saw a 36% reduction in death from all causes, while those treated with only Amvuttra experienced a 35% reduction. Across the entire patient population, Amvuttra significantly improved six-minute walk distance and New York Heart Association classification, among other disease progression measures.

Amvuttra is administered as a subcutaneous injection and works by targeting both mutant and wild-type transthyretin mRNA for degradation. This mechanism reduces serum levels of transthyretin protein and mitigates the buildup of its misfolded forms throughout the body, including the heart, thereby addressing the core pathological process in ATTR-CM.

According to Stifel analysts, the topline data from HELIOS-B are highly encouraging and suggest that vutrisiran could become a blockbuster drug for TTR-cardiomyopathy. They noted the notably robust benefits of Amvuttra, especially when used in conjunction with tafamidis.

The FDA had initially approved Amvuttra in June 2022 for treating ATTR amyloidosis with polyneuropathy, a similar condition affecting the nerves rather than the heart. Should the FDA approve the label expansion for Amvuttra, it would provide a significant boost for Alnylam, especially following the FDA’s rejection in October 2023 of the company’s application to use Onpattro (patisiran) in ATTR-CM due to insufficient evidence of its benefit in this condition.