Alynlam reports positive topline results from Phase 3 heart disease trial

Company’s RNAi drug reduces all-cause mortality and recurrent cardiovascular events in patients with ATTR cardiomyopathy.

RNAi therapeutics company Alnylam Pharmaceuticals has announced eagerly-awaited topline results from its Phase 3 study of vutrisiran, an investigational RNA interference therapeutic for treating transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The study achieved statistical significance on primary and all secondary endpoints in both overall and monotherapy populations.

Treatment with vutrisiran showed a 28% reduction in the composite of all-cause mortality and recurrent cardiovascular events in the overall population, and a 33% reduction in the monotherapy population. Moreover, it reduced all-cause mortality by 36% and 35% in these respective groups.

ATTR is an underdiagnosed and potentially fatal disease of the heart muscle caused by misfolded transthyretin proteins, leading to amyloid deposits in various organs, particularly the nerves and heart. The wild type of the disease (wtATTR) impacts 200,000 to 300,000 people, mainly older adults, and is classified as an age-related disease. The condition is thought to be an underrecognized cause of heart failure, and its prevalence is expected to rise with the aging population.

Marketed by Alynlam as Amvuttra, vutrisiran is an RNAi therapeutic – a type of drug that works by silencing messenger RNA (mRNA) to prevent disease-causing proteins from being made. The technology breakthrough was recognized with the 2006 Nobel Prize for Physiology or Medicine.

The Phase 3 study’s primary endpoint was the reduction of all-cause mortality and recurrent cardiovascular events, which vutrisiran achieved with statistical significance in both the overall and monotherapy populations. Secondary endpoints showed statistically significant improvements in the 6-minute walk test, Kansas City Cardiomyopathy Questionnaire and New York Heart Association Class at Month 30. Additionally, vutrisiran significantly reduced all-cause mortality up to month 42 in both the overall and monotherapy populations.

“I am overjoyed by the results of the HELIOS-B study, which suggest the potential for vutrisiran to be a transformative medicine for patients with ATTR amyloidosis with cardiomyopathy,” said Yvonne Greenstreet, CEO of Alnylam. “Assuming favorable regulatory review, vutrisiran has the potential to become the new standard of care for the treatment of this disease, driving Alnylam’s next era of substantial growth.”

Detailed results have been submitted to the European Society of Cardiology for presentation. Alnylam plans to file a supplemental New Drug Application with the US FDA, and will proceed with global regulatory submissions later this year.

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