Positive topline 18-month results from HELIOS-A phase III study of vutrisiran in patients with hATTR amyloidosis with polyneuropathy.

The final secondary endpoint, reduction in serum TTR levels with vutrisiran, demonstrated non-inferiority relative to the within-study patisiran arm, as expected. In addition, patients treated with vutrisiran showed improvements in exploratory endpoints, including the biomarker NT-proBNP and certain echocardiographic parameters, relative to placebo, and an improvement in technetium uptake relative to baseline in a majority of patients in a planned cohort, providing potential evidence for reduced cardiac amyloid burden. Vutrisiran continued to demonstrate an encouraging safety and tolerability profile. Alnylam previously announced that HELIOS-A met its primary and secondary endpoints at nine months and study results were presented at the 2021 American Academy of Neurology (AAN) Virtual Annual Meeting.

At 18 months, patients treated with vutrisiran showed quantitative improvement across a number of exploratory endpoints. Compared to placebo, patients in the vutrisiran arm demonstrated improvement in the cardiac biomarker endpoint, NT-proBNP, a measure of cardiac stress. In addition, patients treated with vutrisiran also demonstrated improvement in certain echocardiographic parameters, relative to placebo. Finally, in a planned cohort of 48 patients, treatment with vutrisiran was associated with an improvement in technetium uptake in the heart in a majority of patients, providing potential evidence for reduced cardiac amyloid burden.

Vutrisiran demonstrated an encouraging safety profile. There were three study discontinuations (2.5 percent) due to adverse events in the vutrisiran arm during the 18 Month treatment period; the single new discontinuation since Month 9 was an event of cardiac failure considered unrelated to study drug by the investigator. During the 18 Month treatment period, there were two deaths (neither of which was considered related to study drug) and two serious adverse events (SAEs) deemed related to vutrisiran by the study investigator; these deaths and related SAEs all occurred by Month 9 and were previously reported. Treatment emergent adverse events (AEs) occurring in 10 percent or more patients included fall, pain in extremity, diarrhea, peripheral edema, urinary tract infection, arthralgia and dizziness; with the exception of pain in extremity and arthralgia, each of these events occurred at a similar or lower rate as compared with external placebo. Injection site reactions (ISRs) were reported in 5 patients (4.1 percent) and were all mild and transient. There were no hepatic safety concerns.

Vutrisiran is under review by the FDA, the European Medicines Agency (EMA), and the Brazilian Health Regulatory Agency (ANVISA). Vutrisiran has been granted Orphan Drug Designation in the U.S. and the European Union (EU) for the treatment of ATTR amyloidosis. Vutrisiran has also been granted a Fast Track designation in the U.S. for the treatment of the polyneuropathy of hATTR amyloidosis in adults. In the U.S., vutrisiran has received an action date under the Prescription Drug User Fee Act (PDUFA) of April 14, 2022. The Company received Orphan Drug Designation in Japan for transthyretin type familial amyloidosis with polyneuropathy.