Alnylam reports positive late-stage results for RNAi therapy in ATTR cardiomyopathy

Alnylam Pharmaceuticals’ RNA interference (RNAi) therapeutic, Amvuttra (vutrisiran), has shown promising results for patients suffering from transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The efficacy and safety of Amvuttra were assessed in the phase 3 HELIOS-B study, which compared the drug to a placebo in subjects both on and off tafamidis at the start of the trial.

ATTR amyloidosis is a severe and quickly progressing condition marked by the formation of misfolded transthyretin (TTR) proteins. These malformed proteins create amyloid deposits in various parts of the body, including the nerves, heart, and digestive system. There are two types of ATTR amyloidosis: hereditary ATTR (hATTR), caused by a TTR gene mutation affecting around 50,000 people globally, and wild-type ATTR, which occurs without the gene mutation and impacts up to 300,000 individuals worldwide.

The HELIOS-B study achieved its main and secondary goals across all significant subgroups. These subgroups included patients' initial use of tafamidis, the type of ATTR disease, and different severity measures of the condition. Amvuttra operates by lowering serum vitamin A levels in the bloodstream, which in turn diminishes the accumulation of TTR in the body.

The study highlighted that Amvuttra significantly reduced the combination of all-cause mortality and recurrent cardiovascular events in both the overall population and those receiving monotherapy by the 36-month mark. Additionally, it showed marked improvements across all secondary endpoints, including critical indicators of disease progression, in both cohorts.

Furthermore, the investigational RNAi therapeutic exhibited a favorable safety and tolerability profile, aligning with previously established data. Pushkal Garg, the Chief Medical Officer at Alnylam, expressed his enthusiasm about the positive outcomes from the HELIOS-B study. He noted that Amvuttra has the potential to meet the needs of ATTR-CM patients by improving cardiovascular outcomes such as survival, function, and quality of life across all patient groups.

Alnylam is preparing to submit global regulatory applications for Amvuttra in ATTR-CM, with plans to initiate these submissions later this year. This includes filing a supplemental New Drug Application with the US Food and Drug Administration, utilizing a priority review voucher to expedite the process.

In January of the previous year, the National Institute for Health and Care Excellence recommended Amvuttra for the treatment of hATTR amyloidosis.