The U.S. Food and Drug Administration approved Alnylam Pharmaceuticals’ Amvuttra for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

Photo: Yvonne Greenstreet, CEO of Alnylam Pharmaceuticals
It is the fifth approval of an RNAi therapeutic for Alnylam over the past four years and improves on its first generation hATTR therapy Onpattro, which is given by intravenous injection every four weeks whereas Amvuttra is delivered via subcutaneous injection once every three months.
Hereditary transthyretin-mediated (hATTR) amyloidosis is an inherited, progressively debilitating, and fatal disease caused by variants (i.e., mutations) in the TTR gene. TTR protein is primarily produced in the liver and is normally a carrier of vitamin A. Variants in the TTR gene 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. hATTR amyloidosis, represents a major unmet medical need with significant morbidity and mortality affecting approximately 50,000 people worldwide. The median survival is 4.7 years following diagnosis, with a reduced survival (3.4 years) for patients presenting with cardiomyopathy.
“Twenty years ago, Alnylam was founded with the bold vision for RNA interference to make a meaningful impact on the lives of people around the world in need of new approaches to address serious diseases with significant unmet medical needs, such as hATTR amyloidosis. Today, Amvuttra has the potential to change the standard of care for people living with the polyneuropathy of this devastating disease,” said Yvonne Greenstreet, CEO of Alnylam Pharmaceuticals.
The approval is based on positive nine-month results from the HELIOS-A phase 3 study, a global, randomized, open-label, multicenter, phase 3 study that evaluated its efficacy and safety across a diverse group of patients with hATTR amyloidosis with polyneuropathy in which Amvuttra met the primary and secondary endpoints, significantly improving the signs and symptoms of polyneuropathy, with more than 50 percent of patients experiencing halting or reversal of their disease manifestations.
The efficacy of Amvuttra was assessed by comparing the Amvuttra group in HELIOS-A with the placebo group from the landmark APOLLO phase 3 study of Onpattro (patisiran), a randomized controlled study in a comparable patient population.
Amvuttra demonstrated an encouraging safety and tolerability profile with 9 months of dosing and there were no drug-related discontinuations or deaths.
Alnylam expects to launch access to Amvuttra in early July, with value-based agreements to accelerate access.
Amvuttra is under review by the European Medicines Agency (EMA), the Brazilian Health Regulatory Agency (ANVISA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Amvuttra was previously granted Orphan Drug designation in the United States and the European Union for the treatment of ATTR amyloidosis and in Japan for transthyretin type familial amyloidosis with polyneuropathy. A biannual 50mg dosing regimen is under evaluation within the ongoing randomized treatment extension (RTE) period in the HELIOS-A trial. Amvuttra is also being evaluated in the HELIOS-B phase 3 study for the treatment of patients with ATTR amyloidosis with cardiomyopathy, including both hATTR and wild-type ATTR (wtATTR) amyloidosis.
Author: Rare Daily Staff

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