Onpattro Approval Sought for ATTR Amyloidosis With Cardiomyopathy

Alnylam files with FDA for new use for approved therapy

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Alnylam Pharmaceuticals has submitted an application to the U.S. Food and Drug Administration (FDA) asking the agency to approve Onpattro (patisiran) for the treatment of transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy.

Onpattro already is approved to treat familial amyloid polyneuropathy (FAP), a genetic disorder in which toxic tangles of transthyretin — a transport protein in the body — cause nerve damage. In the related condition ATTR amyloidosis with cardiomyopathy, these toxic protein tangles cause damage to the heart.

According to Rena N. Denoncourt, vice president, TTR franchise lead at Alnylam, this application “brings us one step closer to making patisiran available to patients with ATTR amyloidosis with cardiomyopathy,” she said in a company press release.

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The application is supported by data from a Phase 3 clinical trial called APOLLO-B (NCT03997383).

That study enrolled 360 adults with ATTR amyloidosis with cardiomyopathy who were randomly assigned to receive Onpattro or a placebo, administered via infusion into the bloodstream (intravenously) every three weeks for one year.

The trial’s main goal was to assess the impact of treatment on exercise capacity, as assessed by the distance that participants could walk in six minutes. Typically such scores lower over time in patients with cardiomyopathy.

Top-line results showed that the decline in the distance walked was significantly lower for Onpattro-treated patients. In fact, by the trial’s end, these individuals walked on average about 50 feet further than those on the placebo. Onpattro also outperformed the placebo at improving quality of life and reducing markers of heart damage, the results indicated.

The therapy was generally well-tolerated with most side effects being mild or moderate in severity.

Overall, the results suggest that Onpattro “has the potential to improve the functional capacity and quality of life of patients with ATTR amyloidosis with cardiomyopathy, an increasingly recognized cause of heart failure for which there are limited treatment options,” Denoncourt said.

Notably, the APOLLO-B study included patients with both hereditary and wild-type disease — that is, both people whose disease was attributable to an underlying genetic mutation in the gene that provides instructions for making transthyretin protein, and those with no mutation in this gene.

Onpattro is designed to reduce transthyretin protein production using a strategy called RNA interference or RNAi. This essentially involves the medication interfering with how the gene is “read” to make protein. The idea is that by reducing the levels of transthyretin protein there is a reduction of protein toxic tangles.

“The positive results of the APOLLO-B Phase 3 study of [Onpattro] validate the therapeutic hypothesis that [transthyretin] silencing by an RNAi therapeutic may be an effective approach to treating cardiomyopathy of both wild-type and hereditary ATTR amyloidosis,” Denoncourt said.

“This is an important milestone as we work to build an industry-leading franchise for the treatment of ATTR amyloidosis,” she said.