Rare Disease Report

Alnylam Initiates Phase 3 of Givosiran in Acute Hepatic Porphyrias

NOVEMBER 07, 2017
Mathew Shanley
This morning, Alnylam Pharmaceuticals announced that the company’s ENVISION Phase 3 clinical study of givosiran for the treatment of acute hepatic porphyrias (AHPs) is underway.

Givosiran is a subcutaneously administered, investigational RNA interference (RNAi) therapeutic that targets aminolevulinic acid synthase 1 (ALAS1), which when in the presence of downstream enzyme defects of the heme biosynthesis pathway can result in the accumulation of 5-aminolavulinic acid (ALA) and porphobilinogen (PBG), 2 neurotoxic intermediates that cause the symptoms of AHPs and acute intermittent porphyria (AIP).

Givosiran could potentially serve as the first novel treatment approach to successfully and consistently prevent attacks, reduce lingering symptoms, and decrease burden of disease.

Common symptoms of acute prophyrias most commonly affect the central nervous system (CNS), however, the condition has also been associated with severe pain in the abdomen.

Alnylam expects to report interim analysis data from the study in mid-2018, and assuming positive data is collected, hopes to file a New Drug Application with the U.S. Food and Drug Administration (FDA) for givosiran by the end of next year.

“Based on our Phase 1 and Phase 2 open-label extension study results, we believe that givosiran could meaningfully reduce the frequency of attacks requiring hospitalizations and the need for hemin, with an encouraging tolerability profile. As a global, wholly owned program, we are committed to rapidly advancing givosiran and most importantly, if approved, delivering this novel therapy to AHPs patients in need of new options,” said Jeff Miller, General Manager of the givosiran program in a press release.

ENVISION is a randomized, double-blind, placebo-controlled study taking place in more than 20 countries to assess both the efficacy and safety of givosiran in 75 enrolled patients with a documented diagnosis of AHPs. The primary endpoint is the annualized rate of porphyria attacks requiring hospitalization, urgent healthcare visit or hemin administration at home over the 6-month period during which the study is taking place. All patients completing the treatment period will be eligible to continue an open-label extension (OLE) study in which they will receive givosiran for up to 30 months.

Givosiran has previously received Breakthrough Therapy designation from the FDA and Priority Medicines (PRIME) designation by the European Medicines Agency (EMA).

“The disease burden for these patients is dire and can include frequent hospitalizations, severe abdominal pain, neuropsychiatric symptoms, and weakness. The diagnosis of AHPs are often delayed an average of 15 years, further negatively impacting patients’ lives. A once-monthly, subcutaneous injection with acceptable tolerability and the potential to prevent porphyria attacks could be transformational for patients,” said Miller.

For more from Alnylam as they continue development for givosiran and other drugs that could be beneficial to the rare disease community, follow Rare Disease Report on Facebook and Twitter.

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