An Alnyam Pharmaceuticals drug that treats nerve pain caused by an inherited protein disorder has now received results from a pivotal clinical trial that showed it could also help patients suffering from the disease’s potentially deadly effects on the heart. Preliminary data supports expanding the drug’s use to more patients, which will introduce a competitive alternative to Pfizer’s blockbuster drug and allow Alnylam to have a blockbuster of its own.
The primary goal of the Phase 3 study is to show an improvement compared to a placebo in a test that measures how far patients can walk in six minutes.spandex reported Wednesday Those treated with its drug Onpattro showed a statistically significant improvement in this walking test, paving the way for the company to file with regulators later this year.
Cambridge, Massachusetts-based Alnyam shares opened Wednesday at $210 a share, up nearly 48% from Tuesday’s close.
Alnylam’s Onpattro is being developed to treat hereditary transthyretin amyloidosis (TTR), a disease caused by genetic mutations that cause the liver to produce misfolded transthyretin. These abnormal proteins accumulate in tissues and organs throughout the body, causing a wide range of problems.
In the heart, protein deposits lead to enlarged heart walls and impaired heart function. Cardiovascular effects of the disease include cardiomyopathy, abnormal heart rhythms, and heart failure. The disease can also develop as a normal part of aging in people who do not have a mutation in the TTR root gene. This form of the disease primarily affects the heart, leading to cardiomyopathy and heart failure.
The drugs developed by Alnyam work through a mechanism called RNA interference (RNAi). Its products deliver small interfering RNAs that stop genes from making disease-causing proteins. This approach is sometimes called “gene silencing.”
In 2018, Onpattro became the first RNAi drug approved by the FDA in a decision that covers the treatment of nerve pain experienced by TTR patients. According to Alnyam, manifestations of the disease affect about 50,000 people worldwide. The company estimates that TTR with cardiomyopathy affects more than 250,000 people worldwide. The drug had sales of $474.7 million last year, according to Alnyam’s financial report.
To support bringing Onpattro to patients with cardiac manifestations of TTR, Alnylam tested the drug in a Phase 3 study that enrolled 360 adults with inherited or non-genetic disorders. Patients were randomly assigned to receive intravenously administered study drug or placebo for 12 months. After 12 months, all patients received Onpattro in an open-label extension study.
In addition to the six-minute walk test, the study had a secondary objective of measuring changes in quality of life based on the Cardiomyopathy Questionnaire. The study met that goal, but did not publish specific details on results for either endpoint. Full data from the study will be presented Sept. 8 at the International Symposium on Amyloidosis in Heidelberg, Germany, Alnylam said.
“We are very pleased with these results and what they mean for patients, physicians, families, caregivers — everyone in the ATTR amyloidosis community,” Alnylam CEO Yvonne Greenstreet said on a conference call Wednesday morning. , we believe these results show the true power of RNAi’s mechanism of action. By using natural processes to inhibit the production of disease-causing TTR proteins, we have achieved disease-modifying effects on cardiac manifestations of ATTR amyloidosis.”
The study led to non-significant results for one of the secondary objectives, a composite endpoint measuring all-cause mortality, frequency of cardiovascular events, and change from baseline in the six-minute walk test compared to placebo . Efficacy analyses for death identified 4 patients in the Onpattro group and 10 in the placebo group. But the company did not perform formal statistical tests for the last two endpoints, because the small number of patients and the short study duration meant the study could not assess statistical significance.
The only currently available treatment for heart problems caused by TTR is Pfizer’s Vyndaqel, a small molecule designed to bind to and stabilize the abnormal transthyretin protein. The drug generated more than $2 billion in global sales last year, according to Pfizer’s financial report.
With the latest Onpattro results, Alnylam succeeds where BridgeBio Pharma stumbled. BridgeBio’s approach is closer to Pfizer’s. The biotech’s drug, acoramidis, is a small molecule designed to bind and stabilize a problematic protein at the root of TTR. But last December, BridgeBio reports surprising interim data showing the drug did not beat placebo in first part of phase 3 study. BridgeBio is continuing the study, hoping to follow patients for longer periods of time, leading to better outcomes.
A supplemental new drug application for the use of Onpattro to treat TTR-related heart problems should be ready by the end of this year, Greenstreet said.With the recent FDA Approved And the U.S. launch of Amvuttra, a TTR drug that’s less burdensome to patients than Onpattro administered every three weeks, Greenstreet said the latest Phase 3 results “serve as an extension of Alnylam’s TTR franchise.” provides further support to our product. Over time, I believe this could represent a multi-billion dollar opportunity for Alnylam.”
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