FDA to decide on expanding its approval of Onpattro by October

Alnylam seeking therapy approval for ATTR amyloidosis with cardiomyopathy

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) has agreed to review an application from Alnylam Pharmaceuticals seeking the approval of Onpattro (patisiran) for the treatment of transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy.

According to the company, the FDA is expected to announce a decision by Oct. 8. Alnylam submitted a supplemental new drug application (sNDA) asking the FDA to expand the Onpattro’s approval late last year.

“The FDA’s acceptance of our sNDA for [Onpattro] is a positive step forward as we work to bring patients with ATTR amyloidosis with cardiomyopathy a new treatment option that addresses the underlying cause of disease and has the potential to meaningfully improve functional capacity and quality of life,” Rena N. Denoncourt, vice president and TTR franchise lead at Alnylam, said in a company press release.

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Onpattro approved to treat familial amyloid polyneuropathy

Onpattro is already approved to treat familial amyloid polyneuropathy (FAP), a disorder in which mutations in the TTR gene lead to production of an abnormal form of a protein called transthyretin (TTR), which forms toxic aggregates that damage different tissues in the body, particularly nerves.

ATTR amyloidosis with cardiomyopathy is a related condition in which toxic TTR aggregates build up and damage the heart. This often occurs in people with an underlying TTR mutation, referred to as hereditary disease, though it can also affect people without any mutation, which is referred to as wild-type disease.

“ATTR amyloidosis with cardiomyopathy is an increasingly recognized cause of heart failure for which there are limited treatment options,” Denoncourt said.

Alnylam’s application is supported by data from the Phase 3 APOLLO-B (NCT03997383) trial, which tested Onpattro against a placebo in 360 adults who have ATTR amyloidosis with cardiomyopathy. The study included patients with hereditary and wild-type disease. Participants were randomly assigned to receive infusions of Onpattro (0.3 mg/kg) or placebo, every three weeks, for about a year.

The trial’s main goal was to assess exercise capacity, as measured by the distance that participants could walk in six minutes, referred to as 6MWD.

Most of the participants experienced a decline in 6MWD over the course of the year-long study, but patients on placebo tended to decline much faster than those on Onpattro. By the end of the study, the median distance for patients on Onpattro was nearly 50 feet more than for those on placebo.

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Heart-related life quality improved slightly for patients on Onpattro

Standardized assessments of heart-related life quality on average improved slightly for patients on Onpattro, but worsened markedly for those on placebo, with a statistically significant difference between the two groups.

Onpattro also outperformed placebo in its ability to reduce markers of heart damage and TTR levels.

The therapy is designed to decrease TTR production by using a technology called RNA interference. Simplistically, Onpattro interferes with the process by which the TTR gene is read to make TTR, ultimately resulting in lower levels of the protein.

The safety profile of Onpattro in the APOLLO-B study was consistent with data from previous studies. Common side effects associated with Onpattro include upper respiratory infections and infusion-related reactions, such as flushing, back pain, nausea, abdominal pain, shortness of breath, and headache.