Alnylam Submits sNDA for Onpattro in ATTR Amyloidosis with Cardiomyopathy

Alnylam Pharmaceuticals has submitted a supplemental new drug application (sNDA) to the FDA for Onpattro (patisiran) to treat patients with transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy. Onpattro is currently approved to treat polyneuropathy of hereditary ATTR amyloidosis in adults.

In cardiomyopathy, the heart loses its ability to pump blood. In ATTR amyloidosis, the ATTR protein can build up in the heart muscle, leading to shortness of breath and swelling in the legs. Patients with ATTR cardiomyopathy can also have arrhythmias that can lead to stroke or death.

The submission is based on positive results from APOLLO-B, a phase 3 global study that demonstrated the effects of patisiran on functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy. The safety profile in APOLLO-B was consistent with what was observed in APOLLO and in postmarketing use of Onpattro, the company said in a press release. In APOLLO-B, the majority of adverse events were mild or moderate in severity.

The 12-month results from the study were presented at the 18th International Symposium on Amyloidosis (ISA) on Sept. 8, 2022. The 12-month findings across a comprehensive set of exploratory endpoints suggest that treatment with patisiran was associated with favorable impacts on key measures of cardiac stress and injury, NT-proBNP and Troponin I.

Parag Kale, M.D.

The majority of adverse events were mild or moderate in severity. Treatment emergent adverse events occurring in 5% or more patients in the patisiran group included infusion-related reactions, arthralgia, and muscle spasms, In the safety analysis there were five deaths observed in patisiran-treated patients and eight deaths observed in the placebo group.

“The cardiac manifestations associated with ATTR amyloidosis can have a devastating impact on patients’ lives and current treatment options are limited,” Parag Kale, M.D., Staff Cardiologist, Heart Transplant Department at Baylor University Medical Center, said in a press release at the time.