Vutrisiran Reduces Heart Risks for ATTR-CM Patients in Alnylam’s HELIOS-B Trial

Alnylam Pharmaceuticals announced promising results from its HELIOS-B Phase III clinical trial evaluating vutrisiran, an investigational RNA interference (RNAi) therapeutic for treating transthyretin amyloidosis with cardiomyopathy (ATTR-CM).

The data, presented at the European Society of Cardiology Congress 2024, suggest that vutrisiran could significantly reduce the risk of death and heart-related issues, marking a potential treatment breakthrough.

The HELIOS-B results build on earlier success from the HELIOS-A trial, which led to the US Food and Drug Administration (FDA) approval of vutrisiran (Amvuttra) for polyneuropathy associated with hereditary transthyretin-mediated amyloidosis (hATTR). While HELIOS-A focused on nerve damage, HELIOS-B expands vutrisiran’s use to cardiomyopathy.

ATTR-CM is a severe and often fatal condition caused by the buildup of misfolded transthyretin (TTR) proteins in the heart, leading to heart failure.

Vutrisiran works by silencing the gene responsible for producing TTR, reducing both mutant and wild-type TTR proteins. This approach targets the root cause of the disease by degrading the faulty messenger RNA (mRNA) that produces the harmful proteins. Compared to current treatments, vutrisiran’s focus on reducing abnormal protein production could really improve patient outcomes.

Created through Alnylam’s RNAi technology, vutrisiran is part of a growing lineup of Alnylam’s RNAi-based therapies, demonstrating the potential of this approach to treat complex conditions by targeting harmful proteins before they cause damage.

As of March 2024, the FDA has approved six small interfering RNA (siRNA) therapies.

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In the HELIOS-B trial, which included patients with both hereditary and wild-type ATTR-CM, vutrisiran reduced the risk of death and serious heart problems by 28 percent. It also lowered the overall death rate by 31 percent during the 33 to 36-month double-blind period and by 36 percent up to 42 months.

For patients who took vutrisiran as their only treatment, the drug was even more effective, reducing the risk of serious heart problems by 33 percent and lowering the overall death rate by 35 percent up to 42 months. These results suggest that vutrisiran may be more effective as a standalone treatment.

Additionally, vutrisiran helped improve patients’ ability to walk and their overall heart health, an encouraging sign for those in the early stages of the disease.

The HELIOS-B study’s findings are timely as new gene-editing therapies, like the one being studied in MedStar Health’s Phase III MAGNITUDE trial for ATTR-CM, are also being explored. The MAGNITUDE trial uses CRISPR/Cas9 technology to target the genetic source of the disease, potentially offering a one-time treatment.