The U.S. Food and Drug Administration is currently evaluating a supplemental new drug application for vutrisiran, an investigational RNA interference (RNAi) therapeutic, to treat transthyretin amyloid cardiomyopathy (ATTR-CM), Alnylam Pharmaceuticals Inc. announced recently. Alnylam markets vutrisiran under the brand name Amvuttra.
If approved, vutrisiran would become the first U.S. treatment to treat both polyneuropathy and cardiomyopathy linked to ATTR amyloidosis, providing a novel therapeutic option for a serious and often fatal disease.
What is ATTR-CM?
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a rare progressive disease of the heart muscle that leads to congestive heart failure. It occurs when the transthyretin protein produced by the liver is unstable. Symptoms include fatigue; shortness of breath; irregular heart rate or palpitations; swelling of the legs, ankles and stomach; brain fog; wheezing; and dizziness. It often goes underdiagnosed because of a lack of awareness and knowledge of the disease. There is currently no cure for ATTR-CM.
ATTR is caused by the buildup of misfolded transthyretin proteins, leading to damage in the heart, nerves and other organs. The condition includes hereditary and wild-type forms, with cardiomyopathy being a critical manifestation that can progress rapidly.
Read more about ATTR-CM therapies
The FDA previously approved vutrisiran to treat hereditary ATTR polyneuropathy. It works by reducing both mutant and normal transthyretin protein levels, directly targeting the disease’s underlying cause, the company said.
The FDA’s review is based on findings from the Phase 3 HELIOS-B trial. “In HELIOS-B, treatment with vutrisiran improved cardiovascular outcomes, survival, disease progression and quality of life, as compared to placebo, in a population reflective of today’s patients on substantial background treatment,” said Dr. Pushkal Garg, Alnylam’s chief medical officer, in a statement. “We look forward to working with the FDA to support their review of the application and bring vutrisiran to patients with ATTR-CM in the U.S. early next year.”
The HELIOS-B trial studied vutrisiran in patients with ATTR-CM and demonstrated that it improved survival rates, reduced cardiovascular complications and enhanced quality of life compared to placebo, the company said.
The benefits were observed alongside standard treatments for heart failure. Safety data from HELIOS-B revealed that vutrisiran was well-tolerated, with side effects consistent with previous findings, including occasional pain in the extremities and decreased levels of vitamin A, the company said.
Vutrisiran is administered subcutaneously every three months, compared with more frequent treatments required for some other therapies.
If approved, vutrisiran could slow disease progression and improve symptoms in patients with ATTR-CM, potentially extending life expectancy, the company said.
The FDA’s decision is expected by March 2025.