RARE Daily

Alnylam Reports Positive Topline Results from Late-Stage hATTR Study

January 7, 2021

Rare Daily Staff

Alnylam Pharmaceuticals reported topline results from the HELIOS-A phase 3 study of its experimental RNAi therapeutic vutrisiran met its primary and both secondary endpoints at nine months in patients with hATTR amyloidosis with polyneuropathy.

The primary endpoint was the change from baseline in the modified Neuropathy Impairment Score (mNIS+7) at 9 months as compared to historical placebo data from the APOLLO phase 3 study of patisiran. The two secondary endpoints were changes in quality of life assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and gait speed assessed by the timed 10-meter walk test (10-MWT) compared to historical placebo.

Vutrisiran met the primary endpoint and achieved statistically significant results for each of the Norfolk QoL-DN and 10-MWT secondary endpoints. In addition, vutrisiran treatment showed improvement compared to placebo on the exploratory cardiac biomarker endpoint, NT-proBNP. Vutrisiran also demonstrated an encouraging safety and tolerability profile.

Based on these positive results, the company plans to submit a New Drug Application for vutrisiran with the U.S. Food and Drug Administration (FDA) in early 2021, and to follow with regulatory filings in additional countries, such as Brazil and Japan. The company plans to submit a Marketing Authorization Application in the European Union upon obtaining the results of the 18-month analysis, which is expected in late 2021.

“We believe that vutrisiran, as a low-dose, once-quarterly, subcutaneously administered therapy, has the potential to be a highly attractive therapeutic option for patients living with this progressive, life-threatening, multi-system disease,” said Akshay Vaishnaw, president of R&D at Alnylam.

There were two study discontinuations (1.6 percent) due to adverse events in the vutrisiran arm by month 9, both due to deaths, neither of which was considered related to study drug. There were two serious adverse events deemed related to vutrisiran by the study investigator, consisting of dyslipidemia and urinary tract infection. Treatment emergent adverse events occurring in 10 percent or more patients included diarrhea, pain in extremity, fall, and urinary tract infections, with each of these events occurring at a similar or lower rate as compared with historical placebo. Injection site reactions were reported in five patients and were all mild and transient. There were no clinically significant changes in liver function tests.

“We believe that our ATTR amyloidosis franchise will be a significant driver of Alnylam’s growth in the years to come, with the potential to position Alnylam as a top tier biopharma company,” said John Maraganore, CEO of Alnylam.

Vutrisiran has been granted Orphan Drug designation in the United States and the European Union for the treatment of ATTR amyloidosis. Vutrisiran has also been granted a Fast Track designation in the United States for the treatment of the polyneuropathy of hATTR amyloidosis in adults.

Photo: John Maraganore, CEO of Alnylam

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