Phase 3 Trial Testing Givosiran for Acute Hepatic Porphyria Completes Enrollment, Alnylam Announces

A Phase 3 clinical trial evaluating the effects of givosiran, an investigational therapy for acute hepatic porphyria (AHP), has completed patient enrollment, Alnylam Pharmaceuticals announced.

The trial (NCT03338816), called ENVISION, enrolled a total of 94 AHP patients at 36 sites in 18 countries, ahead of schedule and surpassing the initial target of 75 due to high patient demand.

Alnylam expects to report the first interim results of the study by the end of September and data from the trial’s primary objective at the beginning of 2019.

It is also planning to submit a new drug application seeking accelerated approval for givosiran to the U.S. Food and Drug Administration by the end of the year.

“We’re pleased to have completed enrollment in the ENVISION Phase 3 study, and we’re thankful to the porphyria community for their support in helping to raise awareness about the importance of clinical trials in rare diseases,” Akin Akinc, vice president and general manager of Alnylam’s givosiran program, said in a press release.

“The fact that we achieved this important milestone significantly ahead of schedule — in addition to exceeding the initial enrollment target — highlights the urgent demand and high unmet need for novel therapies in this disease setting. We remain committed to advancing givosiran, which we believe has the potential to transform the treatment landscape for patients with AHPs,” he added.

Givosiran is an investigational RNA-based therapy designed to block the activity of the enzyme ALAS1 to prevent the accumulation of toxic molecules that cause AHP.

In April, Alnylam presented promising results from a previous randomized Phase 1 (NCT02452372) trial and Phase 1/2 (NCT02949830) open-label extension studies of givosiran for the treatment of AHP during the European Association for the Study of the Liver Annual International Liver Congress in Paris.

Now, ENVISION, a randomized, double-blind, placebo-controlled, global, multicenter Phase 3 trial, will further assess the safety and effectiveness of givosiran in AHP patients.

Participants will be randomly assigned to receive either 2.5 mg/kg of givosiran or a placebo administered monthly through an injection under the skin for six months.

The trial’s primary objective is to assess the annualized rate of porphyria attacks requiring hospitalization, urgent healthcare visits, or hemin administration at home.

The first interim analysis of the study will focus on measuring ALA — a urinary biomarker whose reduction is correlated with clinical benefits — in approximately 30 patients after three months of treatment.

Secondary goals are to measure the relative improvement in AHP symptoms, including pain, nausea, and fatigue, and general impact on patients’ quality of life.

According to Alnylam, after completing the initial treatment period of six months, all participants will be eligible for an open-label extension study, in which they will be able to receive treatment with givosiran for up to 30 months.