Alnylam Pharmaceuticals’ vutrisiran may boost survival in patients with a heart muscle disease who are already taking a popular background therapy, suggesting that there’s room in the market for new treatments that could soon gain approval.
But it is still uncertain whether vutrisiran would end up complementing other treatment options, or competing against them. Alnylam shares $ALNY fell close to 15% in premarket trading Thursday.
Vutrisiran is an siRNA drug that won FDA approval in 2022 for polyneuropathy due to hereditary transthyretin-mediated amyloidosis, and it’s sold under the brand name Amvuttra. Alnylam is now looking to unlock the drug’s blockbuster potential through a label expansion for transthyretin amyloid cardiomyopathy (ATTR-CM), which affects more than 120,000 people in the US, according to ICER.
Pfizer’s Vyndaqel is currently the only drug approved for ATTR-CM, but Alnylam and BridgeBio are close to getting their own therapies cleared by regulators, which will create a more complex landscape for doctors and patients. One of the major questions has been whether there’s added benefit to using the treatments in combination, or if the newer medicines don’t add enough to be worth the additional cost and complexity.
Data from the Phase 3 HELIOS-B trial appear to suggest an answer. An analysis of the 40% of patients in the 655-participant trial who were also taking Pfizer’s Vyndaqel at baseline showed a 41% reduction in all-cause mortality by 42 months.
Alnylam has suggested they have the data to support combination treatments, but also noted monotherapy data will be key given payer concerns.
Pushkal Garg“You’re seeing some evidence of additive efficacy, and I think that suggests [this class of drugs] is not fully meeting the needs of patients,” Alnylam Chief Medical Officer Pushkal Garg told Endpoints News in an interview ahead of the European Society of Cardiology annual meeting in London, where the data were presented.
But Raj Dasgupta, chief medical advisor for Fortune Recommends, told Endpoints in an email statement that he thinks it’s unlikely many patients will take the drugs together in the real world because the efficacy of the combination is still “unclear” and “insurance companies would probably not cover both drugs at the same time.” He instead said vutrisiran use would probably come from newly diagnosed patients and some potentially switching over from Vyndaqel.
BridgeBio shares $BBIO went up 12% in premarket trading.
Not statistically significant
There are likely to be questions about the results, as well. The analysis wasn’t powered for statistical significance, which will likely raise at least some doubts about whether the effect is as strong as the numbers suggest. While the subgroup data are “very interesting and promising,” they will need to be confirmed in a larger group of patients, Bianca Rocca, associate professor of pharmacology at the Catholic University of Rome, told Endpoints in an interview ahead of the meeting.
In June, topline data from HELIOS-B released showed the trial met its primary endpoint, with vutrisiran slashing the risk of death, heart-related hospital visits and hospitalizations by 28% compared with placebo at 33 months. In the subgroup of 395 patients taking vutrisiran monotherapy, the drug cut the risk of these events by 33%.
Alnylam plans to file for label expansion for ATTR-CM in the US by the end of the year, with a potential approval expected in the first half of 2025, Alnylam’s Garg said. While many prescribers are already familiar with the drug from its polyneuropathy indication, the company will continue its disease education efforts to ensure a smooth rollout in ATTR-CM, he added.
Last year, BridgeBio unveiled data from a Phase 3 test of its small molecule transthyretin stabilizer acoramidis in patients with ATTR-CM which showed the drug cut the rate of hospitalization in half. Acoramidis was also linked with a 25% relative risk reduction in mortality versus placebo at 30 months.
In March, Bayer bought the European rights to BridgeBio’s drug for $310 million in upfront and near-term milestones. Acoramidis is currently under review in Europe with an approval anticipated next year while an FDA decision is expected by Nov. 29. The asset could reach $3 billion in peak sales, TD Cowen analysts said earlier this month.
Amvuttra made $230 million in the second quarter of the year, but Wall Street analysts say it has the potential to hit $2 to $4 billion in annual sales.
Editor’s note: Story updated to include stock reactions.