- After talking up the idea of an accelerated approval last month, Alnylam Pharmaceuticals will slow down its application for givosiran, an RNAi therapy, following discussions with the Food and Drug Administration, the company said Monday.
- The Cambridge, Massachusetts-based drugmaker will now wait for full results from a Phase 3 trial that is testing givosiran as a therapy for a family of severe rare diseases called acute hepatic porphyrias (AHP). Alnylam executives expect to initiate a rolling New Drug Application by the end of the year, with an aim to complete the filing by mid-2019.
- Shares in the biotech were down nearly 2% in Monday morning trading, as investors weighed the importance of the new regulatory timeline.
While this update does not significantly change industry expectations for givosiran, it does reflect that the Food and Drug Administration may have been less enthusiastic than Alnylam on its initial Phase 3 data.
The biotech announced interim results from its ENVISION study on Sept. 27, touting its belief that a reduction in urinary aminolevulinic acid levels would satisfy U.S. regulators as a surrogate endpoint "reasonably likely to predict clinical benefit."
Now, the company will wait for full results as part of its givosiran application, with an Alnylam executive adding that results are "expected much earlier than originally planned" after completing full enrollment with 94 patients ahead of schedule.
"Based on our positive Phase 1/2 clinical results presented earlier this year and the positive interim analysis results from the ENVISION Phase 3 trial, we're encouraged by givosiran's potential to make a difference in the lives of AHP patients," Akin Akinc, a company vice president, said in an Oct. 15 statement.
Perhaps one concern weighing on the minds of both investors and regulators is givosiran's safety profile. The interim data for 43 patients found 22% reported serious adverse events compared to 10% on placebo. One patient discontinued treatment after breaking a protocol-defined stopping rule of a liver transaminase increase.
Instead of working off the interim data, regulators will be able to assess the primary endpoint of annualized attack rate after six months of treatment.
One biotech analyst shrugged off the update as a reasonable delay, noting the "modest gap between recent interim results and the upcoming complete results from ENVISION," and reiterated confidence that safety concerns will not overshadow the efficacy and need for the therapy.
"Overall, we find it decidedly unlikely that either regulators or AHP recurrent attack patients will find givosiran's existing safety profile a substantial barrier to approval and adoption," B. Riley FBR analyst Madhu Kumar wrote in an Oct. 15 note to investors.
Alnylam is expected to deliver a topline readout in early 2019 for givosiran. The biotech recently launched its first therapy after receiving a landmark FDA approval in August for Onpattro (patisiran) to treat a peripheral nerve disease caused by hereditary ATTR amyloidosis.