Alnylam Waiting Until 2024 for Safety, Efficacy Results on Amvuttra
Pharmaceutical will not conduct interim analysis in Phase 3 clinical trial
Alnylam Pharmaceuticals will not conduct an interim analysis of its Phase 3 clinical trial testing Amvuttra (vutrisiran) in people with a form of heart disease called transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy.
Instead, the company will wait for the initial findings of final analyses of key safety and efficacy information available from the ongoing HELIOS-B (NCT04153149) trial, which is slated for completion in June 2025.
“The study remains on track for top-line results in early 2024,” Alnylam stated in a recent corporate update,
An interim analysis is conducted at any time prior to a trial’s formal completion to assess and compare treatment groups with respect to efficacy or safety. The goal of this type of analysis is to terminate a study ahead of time, which may happen if a treatment’s efficacy has already been clearly established, or in the event of unacceptable adverse effects.
In the update, the company announced that Amvuttra has been approved in the U.K. as a treatment for familial amyloid polyneuropathy (FAP), specifically for people with stage 1 or stage 2 polyneuropathy. The European Commission announced a similar decision in September.
Amvuttra as a treatment for FAP
The therapy was approved by the U.S. Food and Drug Administration (FDA) in June to treat FAP, and has been approved for the same indication in Japan, according to Alnylam.
Amvuttra works by lowering the production of transthyretin, the faulty protein that builds up in peripheral nerves — those outside the brain and spinal cord — leading to nerve damage, or polyneuropathy, in people with FAP. In these patients, this happens because of mutations in the TTR gene, which contains instructions for making transthyretin.
Specifically, Amvuttra was designed to bind to TTR messenger RNA (mRNA) — the molecule that serves as a template for the production of transthyretin — triggering a process called RNA interference that promotes mRNA destruction. Without its mRNA, the production of the faulty transthyretin protein that causes FAP is prevented.
Its mechanism of action is identical to that of Onpattro (patisiran), an approved FAP therapy also developed by Alnylam. However, Amvuttra is more stable, potentially allowing for longer-lasting effects, less frequent dosing, and lower healthcare costs.
Alnylam also expects to announce results in coming months on a potential new biannual dosing regimen for Amvuttra. Its safety and efficacy in people with FAP are now being investigated in two Phase 3 trials that are part of the HELIOS program.
In HELIOS-A (NCT03759379), participants are receiving under-the-skin (subcutaneous) injections of 25 mg of Amvuttra, once every 12 weeks, or about three months, or Onpattro, delivered by intravenous infusions (directly into the bloodstream) every three weeks.
However, according to Alnylam, administration of Amvuttra given twice a year at a dose of 50 mg, is as effective at blocking the production of transthyretin as when given every three months at a lower dose of 25 mg.
In the update, the company also reinforced its plans to submit, by year’s end, a supplemental new drug application (sNDA) to the FDA seeking the approval of Onpattro for patients with ATTR amyloidosis with cardiomyopathy. This comes on the heels of positive data from the Phase 3 APOLLO-B trial (NCT03997383), in which Onpattro helped preserve functional ability and improve life quality in these patients.
ATTR amyloidosis is a group of disorders in which transthyretin forms toxic clumps that accumulate in different body tissues, including the heart. FAP is a hereditary form of ATTR amyloidosis.
“[We] are encouraged by the positive APOLLO-B Phase 3 results for patisiran in patients with ATTR amyloidosis with cardiomyopathy,” said Yvonne Greenstreet, CEO of Alnylam.
“We are on track to submit an sNDA for Onpattro by year-end and hope to bring this treatment option to patients in 2023 assuming successful regulatory review and approval,” Greenstreet said.