- Alnylam Pharmaceuticals on Friday disclosed new results supporting the case for a new drug it's been developing for transthyretin amyloidosis, or TTR, a rare genetic disorder that's become a competitive space among drugmakers.
- Alnylam said last year that the drug, an injectable medicine called vutrisiran, reduced the neurological symptoms associated with the disease after nine months in a Phase 3 trial. Those benefits have now held up for 18 months, and Alnylam has seen early indications the drug may help with heart-related symptoms of TTR as well.
- Drug regulators in the U.S., Europe and elsewhere are currently reviewing vutrisiran, which is meant to be a more convenient and longer-lasting version of Alnylam's top-selling drug, Onpattro. The Food and Drug Administration is expected to make a decision by April 14.
For many years, the only treatments for TTR — a rare and potentially deadly disease — were liver transplants and a generic pill that could help slow the nerve damage many patients experience.
But the outlook, at least for those who have inherited the disease rather than acquired it later on, has changed significantly of late. Since 2018, three medicines from Alnylam Pharmaceuticals, Ionis Pharmaceuticals and Pfizer have been approved in the U.S. Alnylam's Onpattro and Ionis' Tegsedi, two RNA-based medicines, are cleared for those with neurological symptoms. Pfizer's drug Vyndamax is authorized for those with heart problems.
Several other drugmakers have since piled into the space, aiming to one-up existing treatment options and help a broader group of patients. In the past year alone, AstraZeneca and Novo Nordisk have each acquired TTR medicines, while a gene editing drug from Intellia Therapeutics has shown early promise.
Alnylam, too, has been preparing for the competition with a follow-on drug of its own in vutrisiran. Unlike Onpattro, which is given via infusion every three weeks, vutrisiran is administered every three months as a subcutaneous injection. Alnylam is testing a twice-yearly regimen as well.
The results disclosed Friday are notable, as the drug looks "highly efficacious" after 18 months of treatment and continues to have "best-in-class potential," wrote Stifel analyst Paul Matteis. But they don't definitively answer perhaps the biggest question hanging over Alnylam: whether its two drugs can help TTR patients with a faster-moving, deadlier, and far more common version of the disease characterized by heart problems.
Confidence among Wall Street analysts and investors had been high that Alnylam's drugs would succeed. But that changed when a medicine from BridgeBio surprisingly failed in December due, in part, to better-than-expected results from placebo recipients. BridgeBio's stock plunged on the results, and Alnylam shares were dragged down as well.
Alnylam said Friday that patients treated with vutrisiran had positive signs on heart-related biomarkers and scans, each of which were exploratory measures of its study. But the drug's true impact on heart problems won't be known until a trial specifically designed for so-called TTR cardiomyopathy patients produces results in 2024.
Still, important answers could come before that study reads out. Alnylam is expecting results from a trial of Onpattro in TTR cardiomyopathy patients — a trial known as APOLLO-B — by the middle of the year.
The new results are "good to see," Matteis wrote, "though the direct readthrough onto APOLLO-B is debatable."