Alnylam Poised for Fourth Drug Approval with Strong Phase III hATTR Results

Alnylam CEO_Keith Bedford/Boston Globe via Getty

Alnylam CEO John Maraganore pictured above. Photo by Keith Bedford/The Boston Globe via Getty Images.

Boston-based Alnylam Pharmaceuticals is closing in on the potential approval of its fourth therapeutic following positive topline results from the Phase III study of vutrisiran in patients with hereditary transthyretin (TTR)-mediated amyloidosis (hATTR) amyloidosis with polyneuropathy.

This morning, Alnylam announced vutrisiran met primary and all secondary endpoints, demonstrating statistically significant improvements in progression of neuropathy, quality of life (QOL), and gait speed, relative to placebo after nine months. The primary endpoint of the Phase III HELIOS-A study was the change from baseline in the modified Neuropathy Impairment Score (mNIS+7) at nine months as compared to historical placebo data from the APOLLO Phase III study of patisiran.

Additionally, a majority of patients in the Phase III HELIOS-A study showed reversal of disease manifestations with improvements in neuropathy impairment and QOL, relative to baseline.

Based on the findings from the HELIOS-A study, Alnylam intends to submit a New Drug Application for vutrisiran this year in the United States and follow that up with regulatory filings in other countries. Alnylam will seek approval in the European Union after an 18 month analysis, which is expected later this year.

Akshay Vaishnaw, head of R&D at Alnylam, said vutrisiran has the potential to be a highly attractive therapeutic option for patients living with hATTR, a progressive, life-threatening, multi-system disease.

TTR-mediated amyloidosis (hATTR) is an inherited, progressively debilitating, and often fatal disease caused by mutations in the TTR gene. Those mutations cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory-motor neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations.

Vutrisiran is an investigational RNAi therapeutic under development for treatment of ATTR amyloidosis, which encompasses both hereditary (hATTR) and wild-type (wtATTR) amyloidosis. The medication targets specific messenger RNA, blocking the production of wild-type and variant transthyretin (TTR) protein before it is made, according to Alnylam. The potential approval of vutrisiran will complement Alnylam’s Onpattro (patisiran), which was the world’s first RNAi therapeutic approved for the treatment of nerve damage in adult patients with hereditary transthyretin-mediated amyloidosis.

Alnylam Chief Executive Officer John Maraganore said the results from the HELIOS-A study reinforce the company’s commitment to developing a franchise of medications for the treatment of ATTR amyloidosis. And that franchise, he added, is expected to be a significant driver of Alnylam’s growth in the years ahead.

“Indeed, the vutrisiran results from HELIOS-A now serve as a second example of the potential for RNAi therapeutics to have a meaningful impact for patients, showing the ability to halt and potentially even reverse polyneuropathy manifestations of the disease. Furthermore, our robust development program, including the APOLLO-B and HELIOS-B studies, investigates the potential of patisiran and vutrisiran, respectively, to treat the cardiac manifestations of disease across a broad spectrum of patients with ATTR amyloidosis,” Maraganore said in a statement.

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.

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