Advisory meeting about Onpattro for ATTR-CM set for September
A final decision about expanding the therapy's label is expected in October
A U.S. Food and Drug Administration (FDA) advisory committee will meet Sept. 13 to discuss Alnylam Pharmaceuticals‘ application of Onpattro (patisiran) for treating ATTR amyloidosis with cardiomyopathy (ATTR-CM), according to the company.
Data from the placebo-controlled Phase 3 APOLLO-B clinical trial (NCT03997383) will be reviewed at the upcoming meeting of the Cardiovascular and Renal Drugs Advisory Committee and the FDA will consider its opinion when it makes a final decision about Onpattro’s approval for ATTR-CM. That decision is expected by Oct. 8.
Onpattro is approved in the U.S. for people with familial amyloid polyneuropathy, a hereditary disease wherein mutations in the TTR gene cause the toxic accumulation of an abnormal form of the transthyretin (TTR) protein in cells, especially nerve cells.
ATTR-CM is a related disease where toxic TTR clumps accumulate primarily in the heart, leading to heart damage. While it can be caused by TTRÂ mutations, ATTR-CM may also occur without such mutations.
Slower declines in exercise capacity with Onpattro
Delivered via infusion into the bloodstream, Onpattro is designed to suppress TTR production. For this reason, Alnylam expects the therapy will also be effective for ATTR-CM. The company asked the FDA late last year to expand Onpattro’s label to include the condition.
The application is backed by data from the global Phase 3 APOLLO-B study, launched in 2019. A total of 360 adults with ATTR-CM were randomly assigned to receive either Onpattro (0.3 mg/kg) or a placebo once every three weeks for about a year.
The patients given Onpattro saw slower declines in exercise capacity, which was measured by the six minute walk distance (6MWD) test, after a year than those taking a placebo. And while quality of life improved slightly in Onpattro-treated patients, it notably worsened among the placebo group, with the difference between them being statistically significant.
The trial’s participants were able to enroll in the study’s open-label extension phase, where all are being treated with Onpattro for up to three years.
The 6MWD declines were slower for those originally assigned to Onpattro — about 1.5 years of treatment altogether — than among those who’d switched from the placebo after a year, a recent interim analysis after six months in the extension indicated.
But the participants originally given a placebo saw declines in the 6MWD test after six months of Onpattro treatment that were two times lower than those observed when they were taking a placebo.”
Moreover, those who’d been on Onpattro since the beginning exhibited stable life quality and markers of heart stress and injury, whereas those initially on a placebo saw life quality declines after six months in the extension phase as well as increased markers of heart stress/injury.
The safety profile of Onpattro in APOLLO-B has been largely consistent with previous studies. The most common side effects were infusion-related reactions.
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