Alnylam Pharmaceuticals completes patient enrollment for Phase 3 trial of givosiran in acute hepatic porphyrias

Alnylam Pharmaceuticals has announced the completion of patient enrollment for its pivotal phase 3 trial, ENVISION, which evaluates the efficacy of givosiran in treating acute hepatic porphyrias (AHPs), a group of rare genetic diseases. The trial marks a critical step forward in the development of targeted therapies for these debilitating conditions.

The ENVISION trial has successfully enrolled 94 patients at 36 sites across 18 countries, reflecting the global need for new treatments in the realm of rare diseases. These patients were randomized to receive either 2.5 mg/kg of givosiran or a placebo, administered subcutaneously once a month over a six-month period. The primary goal of this trial is to measure the annualized rate of porphyria attacks that require hospitalization, urgent healthcare visits, or hemin administration at home.

Developed by Alnylam Pharmaceuticals, givosiran is an RNA interference (RNAi) therapeutic that targets aminolevulinic acid synthase 1 (ALAS1), a key enzyme in the heme synthesis pathway that is linked to the pathology of AHPs. By reducing the activity of ALAS1, givosiran aims to decrease the elevated levels of neurotoxic intermediates that cause the severe, debilitating symptoms of AHPs.

Alnylam plans to report interim results from the ENVISION trial by the end of September, with a focus on the reduction of urinary aminolevulinic acid (ALA) levels—a surrogate biomarker expected to predict clinical benefit. Final results regarding the primary endpoint of annualized attack rate are anticipated in early 2019. Depending on these outcomes and the safety profile observed, Alnylam intends to pursue an accelerated approval pathway for givosiran, with plans to submit a New Drug Application (NDA) to the U.S. FDA around the end of 2018.

Akin Akinc, Vice President and General Manager of the Givosiran Program at Alnylam Pharmaceuticals, expressed optimism about the trial’s progress: “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. 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.”

The successful advancement of givosiran through clinical trials not only underscores the potential of RNAi technology in treating rare diseases but also highlights the collaborative effort between researchers, patients, and advocacy groups to address these challenging medical conditions. As Alnylam moves closer to potentially bringing givosiran to market, the healthcare community watches with anticipation, hopeful for a new and effective treatment option for patients suffering from acute hepatic porphyrias.