Alnylam Pharmaceuticals, which specializes in developing RNA interference (RNAi) therapeutics to treat genetic diseases, has announced promising clinical trial results for their drug Amvuttra® (vutrisiran) among patients with transthyretin amyloid cardiomyopathy (ATTR-CM). The HELIOS-B Phase III trial showed that the drug significantly reduced the risk of death or recurrent cardiovascular events among study participants.
In ATTR-CM, a rare, potentially fatal and progressive disease, the protein transthyretin (TTR) weakens and becomes misshapen, building up in the heart, nerves and other organs. This buildup makes it difficult for the heart to function properly. Patients can develop polyneuropathy, cardiomyopathy or both.
Positive Results
Alnylam, based in Cambridge, Massachusetts, reported that patients receiving Amvuttra had a 28% lower risk of death or recurrent cardiovascular events compared to those receiving a placebo. This result included patients who were also receiving Pfizer’s Vyndamax® (tafamidis), a TTR stabilizer. For the 60% of participants receiving only Amvuttra, the risk reduction was even higher at 33%. “I’m thrilled by these overwhelmingly positive data from the HELIOS-B study,” said Pushkal Garg, Chief Medical Officer of Alnylam, in a statement. “The results showed that vutrisiran improved cardiovascular outcomes, including survival, function and quality of life in all patient groups with ATTR cardiomyopathy. We are moving with urgency to file these compelling data with regulators to bring this medicine to patients around the world,” he added. The company reported that the trial results included findings of statistical significance on several secondary endpoints for both patient populations, bolstering the results.
Analysts and Investors React
Analysts praised the results as they await more detailed data on the combination of vutrisiran with tafamidis. “This is impressive and shows vutrisiran is highly effective in both naïve and tafamidis-experienced patients…and supports broad use,” said William Blair analyst Myles Minter. The positive news caused Alnylam’s stock to surge by 36% in pre-market trading.
The Potential for Amvuttra
Amvuttra is already approved for treating hereditary ATTR-polyneuropathy. Alnylam estimates that ATTR-CM is ten times more prevalent, presenting a significant market opportunity. “The results of HELIOS-B show the true power of the RNAi mechanism of action, supporting what we believe to be a highly differentiated therapeutic profile and positioning vutrisiran as a new standard of care in ATTR-cardiomyopathy,” said Alnylam CEO Yvonne Greenstreet.
Combination Therapy vs Monotherapy
One question for researchers was whether Amvuttra could enhance the effects of Pfizer’s tafamidis. Although details have not been reported, Alnylam’s chief medical officer, Pushkal Garg, mentioned seeing “evidence of additive effects” in the combination group. Tafamidis, marketed as Vyndaqel® or Vyndamax, is a formidable competitor, generating $3.3 billion in global sales in 2023.
Alnylam also reported Amvuttra’s efficacy as a single agent. The drug reduced the risk of death from any cause by 34.5% in the monotherapy group and by 35.5% in the overall study population. “For a disease where the median survival is two and a half to five and a half years, what patients and physicians really want is a clear impact on mortality,” said Alnylam’s chief commercial officer, Tolga Tanguler. Amvuttra’s effects manifest early and grow over time, enhancing its appeal.
Next Steps
Alnylam plans to seek regulatory approvals later this year and use a priority review voucher for the FDA application. “These remarkable results of vutrisiran in a contemporary population of patients with ATTR-cardiomyopathy with clinical benefits seen on every single one of these rigorous set of endpoints highlight the power of RNAi mechanism of action and suggest that vutrisiran has the potential to become the new standard of care,” Garg said.
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