• Alnylam’s experimental therapy for acute hepatic porphyria met its primary goal of reducing porphyria attacks versus placebo in a Phase 3 study, the company said Wednesday, marking the second time the biotech has succeeded in late-stage testing of an RNAi therapeutic. 
• The treatment, called givosiran, also showed statistically significant benefits across five secondary endpoints in the ENVISION trial, Alnylam said. On the other hand, the experimental therapy failed to meet the threshold for success in four other secondary goals, including daily worst pain and daily worst nausea. 
• Patients taking givosiran reported more adverse events and more serious adverse events than those on placebo, though the company said it believes the safety and tolerability profile of the therapy is “encouraging, especially in this high unmet disease.”

Alnylam plans to use the study to finish approval applications in the U.S. and Europe in mid-2019.

The efficacy results are strong, SVB Leerink analyst Mani Foroohar wrote in a Mar. 6 note to clients. Even so, the safety findings from the trial are “materially worse than expected,” he said.

About 21% of patients in the givosiran arm suffered serious adverse events during the study, compared with about 9% on placebo, according to Alnylam. Some of that can be attributed to the liver disease already present in the patients enrolled in the study, but Foroohar said investors should be alert to the possibility that results constitute a potential safety signal. 

Givosiran works by interfering with messenger RNA, preventing the cellular messages that encode for disease-causing proteins from carrying out their task. If approved, it would be Alnylam’s second RNAi therapy on the market, following last year’s approval of Onpattro (patisiran). The FDA’s OK of Onpattro marked a major milestone for the RNAi field, although commercial sales to date have been modest. 

Givosiran uses a different delivery system than Onpattro. The rest of Alnylam’s pipeline depends on the technology used to deliver givosiran, giving the results from ENVISION broader significance for the biotech. 

Acute hepatic porphyria is a family of rare diseases that often causes hospitalizations and pain and can cause life-threatening attacks. About 5,000 patients in the U.S. suffer sporadic attacks, while about 1,000 have recurrent attacks, according to a company presentation.

The Phase 3 trial included 94 patients, representing the largest interventional study ever conducted for AHP, according to Alnylam. The full results will be presented on April 13 at a meeting of the European Association for the Study of the Liver in Vienna, Austria.