APOLLO-B Trial of Onpattro Fully Enrolls Patients with Heart Disease

Enrollment is now completed in the Phase 3 APOLLO-B trial, which is assessing the safety and efficacy of Onpattro (patisiran) to treat heart disease in people with transthyretin-mediated (ATTR) amyloidosis, a group of conditions that includes familial amyloid polyneuropathy (FAP).

The study (NCT03997383) has enrolled more than 300 participants across 90 sites in more than 20 countries, according to Alnylam Pharmaceuticals, the therapy’s developer and trial sponsor.

“Today’s milestone marks an important step forward as we continue to study the safety and efficacy of patisiran in the treatment of cardiovascular-related manifestations of ATTR amyloidosis,” Rena Denoncourt, vice president and TTR franchise lead at Alnylam, said in a press release.

“We look forward to announcing topline APOLLO-B results in mid-2022,” she added.

ATTR amyloidosis comprises a group of conditions in which the protein transthyretin forms abnormal deposits that accumulate and damage tissues and organs. FAP is a specific type of ATTR amyloidosis caused by mutations in the gene that provides instructions for making transthyretin, in which protein deposits mainly accumulate and damage nerves, leading to the onset of a condition known as polyneuropathy.

Onpattro uses a technology called RNA interference, or RNAi, to lower the levels of transthyretin protein in the body. It is approved to treat adults with FAP in the U.S., Europe, Japan, Canada, Switzerland, and Brazil.

The protein buildup that occurs in FAP and other types of ATTR amyloidosis can also damage the heart and lead to the onset of cardiomyopathy — diseases of the heart muscle that render the heart unable to perform its normal function of pumping blood throughout the body. Cardiomyopathy can also lead to heart failure, which is a leading cause of death among people with ATTR amyloidosis.

The purpose of APOLLO-B is to assess the safety and efficacy of Onpattro in adults, ages 18–85, with ATTR amyloidosis who have cardiomyopathy.

The trial “was initiated based on encouraging data from previous studies that support further investigation of patisiran in ATTR amyloidosis patients with cardiomyopathy,” Denoncourt said. These included data from the Phase 3 APOLLO trial (NCT01960348), which showed that Onpattro was able to lower the levels of a heart strain marker and reduce the thickness of the heart’s lower left chamber — a hallmark of heart failure — in adults with FAP.

Participants in APOLLO-B will receive 0.3 mg/kg of the medication or a placebo, administered through an infusion directly into the bloodstream every three weeks, for a period of one year.

The trial’s primary goal is to evaluate changes in scores on the six-minute walk test, which measures the distance a person can walk in six minutes. This test is commonly used as a measure of physical fitness and exercise capacity in people who are able to walk.

Researchers will also evaluate the effects of treatment on health-related quality of life, heart-related biomarkers, and other measures of heart disease relevant to ATTR amyloidosis.

After the year-long placebo-controlled portion of the trial, participants will have the option to enter into an open-label extension study (NCT02510261), in which all participants will be given Onpattro.