RARE Daily

Alnylam Reports Positive Topline Results from Phase 3 Study in ATTR-CM

June 24, 2024

Rare Daily Staff

Alnylam Pharmaceuticals said topline results from its HELIOS-B phase 3 study of its experimental RNAi therapy vutrisiran met its primary endpoint and key secondary endpoints in ATTR amyloidosis with cardiomyopathy.

The study demonstrated a statistically significant reduction in the composite of all-cause mortality and recurrent cardiovascular events during the double-blind period in both the overall population of ATTR amyloidosis with cardiomyopathy (ATTR-CM) and in the monotherapy population.

The study also demonstrated statistically significant improvements across all secondary endpoints in both the overall and monotherapy populations. This includes key measures of disease progression: 6-minute walk test, Kansas City Cardiomyopathy Questionnaire and New York Heart Association Class at Month 30. Treatment with vutrisiran also reduced all-cause mortality in the overall population and in the monotherapy population up to Month 42. This was a pre-specified, intent-to-treat analysis that included up to six months of data from the open-label extension.

“The results showed that vutrisiran improved cardiovascular outcomes, including survival, function and quality of life in all patient groups with ATTR cardiomyopathy,” said Pushkal Garg, chief medical officer of Alnylam. “We are moving with urgency to file these compelling data with regulators to bring this medicine to patients around the world.”

Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating and fatal disease caused by misfolded transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart and gastrointestinal tract. Patients may present with polyneuropathy, cardiomyopathy, or both manifestations of disease. There are two different forms of ATTR – hereditary ATTR (hATTR), which is caused by a TTR gene variant and affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant and impacts an estimated 200,000 – 300,000 people worldwide.

Vutrisiran is an RNAi therapeutic that delivers rapid knockdown of mutant and wild‑type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, Vutrisiran is approved and marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Vutrisiran is also in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM), which encompasses both wild-type and hereditary forms of the disease.

In the HELIOS-B study, vutrisiran demonstrated encouraging safety and tolerability, consistent with its established profile. Rates of adverse events, serious adverse events and adverse events leading to study drug discontinuation were similar between the vutrisiran and placebo arms. No adverse events were seen ≥3 percent more frequently in the vutrisiran arm compared to the placebo arm.

Detailed results from the HELIOS-B study have been submitted as a late-breaking abstract to the European Society of Cardiology for presentation. The company plans to proceed with global regulatory submissions starting later this year, including filing a supplemental New Drug Application with the U.S. Food and Drug Administration using a Priority Review Voucher.

Photo: Pushkal Garg, chief medical officer of Alnylam

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