Image of a heart with a DNA double helix in front of it to indicate cardiovascular disease and the impact of transthyretin amyloid cardiomyopathy (ATTR-CM) which can be treated with vutrisiran.
Credit: iStock/SvetaP DNA double helix: iStock/Kagenmi

RNA therapeutics specialist Alnylam reports positive Phase III results for its RNA interference (i) therapy vutrisiran for treatment of the heart condition transthyretin amyloid cardiomyopathy (ATTR-CM).

There are different types of amyloidosis, where abnormal proteins build up in different organs around the body. People with ATTR-CM have a build up of misfolded transthyretin protein around the heart, leading to cardiomyopathy-like symptoms and heart failure.

The exact prevalence of the condition is hard to estimate, as it is easy to misdiagnose as a different form of heart disease. However, recent estimates suggest that around 20% of all heart failure cases may be due to ATTR-CM, with around 5000–7000 new cases identified annually in the U.S.

The FDA approved vutrisiran, under the brand name Amvuttra, for treatment of ATTR with polyneuropathy, where the misfolded protein affects the nerves in 2022. However, the Phase III clinical trial results reported this week show that vutrisiran is also effective in patients with ATTR-CM, thought to be a much larger patient group.

The HELIOS-B study included 655 patients with ATTR-CM (both hereditary and wild-type forms). Half the patients received placebo and half vutrisiran once every three months for up to 36 months. Around 40% of patients in the study were taking Pfizer’s ATTR drug tafamidis on enrollment.

The trial met its primary endpoint and significantly reduced a combination of all-cause mortality and cardiac events by 28% in patients already receiving tafamidis by 33% in patients only given vutrisiran.

Secondary endpoints in the trial included improvements in disease progression measures such as: the six-minute walk test, Kansas City Cardiomyopathy Questionnaire and New York Heart Association Class. The trial investigators also recorded significant improvements in all secondary measures in all the patients given vutrisiran (both combination and monotherapy). At month 42, all-cause mortality was reduced by 35% and 34%, respectively, in the overall and monotherapy groups.

Adverse events were monitored carefully and were similar between the placebo and vutrisiran arms of the study, with no serious safety concerns raised.

“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.”

The company is now planning to file for approval for vutrisiran in this indication at the FDA and other regulatory authorities around the world.

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