Alnylam is facing a major challenger to its first approved drug, Onpattro, from Pfizer’s Vyndaqel just over a year into its launch. But the company now has another drug approval to bolster its portfolio––although analysts have expressed some concern about its safety profile.
The FDA approved Givlaari (givosiran) on Tuesday––well ahead of its February decision deadline––as a treatment for acute hepatic porphyria, a genetic disorder resulting in the buildup of toxic porphyrin molecules.
Givlaari is now Alnylam’s second drug to market, joining Onpattro for peripheral nerve disease caused by hereditary transthyretin-mediated amyloidosis (hATTR).
The FDA based its approval off results from a phase 3 trial showing Givlaari beat out placebo at reducing the annualized rate of composite porphyria attacks including those requiring hospitalization, an urgent healthcare visit, or an administration of hemin, which is used to treat porphyria attacks.
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Givlaari also met five of its nine secondary endpoints, including several specific to patients with acute intermittent porphyria, the most common subset of AHP. It did not meet statistical significance for the remaining secondary endpoints, including daily worst fatigue, daily worst nausea and the physical health component of a quality-of-life survey.
However, Givlaari’s safety profile left much to be desired, analysts noted.
The drug’s safety profile was “materially worse than expected,” with serious side effects affecting the Givlaari group at nearly double the rate of the placebo group, at 21% versus 9%, Leerink analysts Mani Foroohar and Rick Bienkowski wrote in March.
Adverse events on the whole occurred at roughly the same rate in both groups, in 90% of Givlaari patients and 80% of placebo patients.
“While these patients have baseline liver disease, and can be attributable to some of the underlying safety events, the more than double SAEs exhibited in the treatment arm compared to placebo could be signs of a safety signal,” the analysts wrote.
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In the meantime, Alnylam reported worldwide Onpattro sales of $46.1 million—largely in line with consensus of $45.5 million—with $33.6 million of that coming from the U.S. Though the RNAi drug’s U.S. sales marked 19% growth quarter-over-quarter, its quarterly haul was still well behind Vyndaqel’s.
