March 06, 2019
2 min read

Givosiran reduces annual attacks, ALA levels in acute hepatic porphyria

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

Alnylam Pharmaceuticals announced that givosiran, an investigational RNAi therapeutic in development for the treatment of acute hepatic porphyria, met its ENVISION phase 3 primary efficacy endpoint of reduction in the annualized rate of composite porphyria attacks compared with placebo, according to a press release and conference call.

“Patients living with [acute hepatic porphyria (AHP)] experience debilitating and sometimes life-threatening neurovisceral attacks as well as chronic disease manifestations which negatively impact their quality of life,” Akshay Vaishnaw, MD, PhD, president of research and development at Alnylam, said in the release. “Based on these results, we believe givosiran has the potential, if approved, to be a transformative medicine for AHP patients and their families.”

The study comprised 94 patients with AHP including 89 patients with acute intermittent porphyria (AIP). The researchers enrolled the patients from sites in 18 countries and randomly assigned them to receive either givosiran or placebo.

At 6 months, givosiran met the primary endpoint in patients with AIP (P < .00000001). Givosiran also met the following secondary reduction endpoints with significant outcomes compared with placebo (P < .0001):

  • urinary aminolevulinic acid (ALA) synthase levels at 3 months in AIP patients;
  • urinary ALA levels at 6 months in AIP patients;
  • urinary porphobilinogen levels at 6 months in AIP patients;
  • annualized days of administered hemin doses in AIP patients; and
  • annualized attack rate in patients with AHP (including AIP).

Five patients with renal dysfunction at baseline developed chronic kidney disease during the study but did not discontinue treatment. One patient discontinued treatment due to an increase in alanine aminotransferase levels higher than 8 times the upper limit of normal, which was resolved. The investigators report no deaths during the study.

The 93 patients who completed the study enrolled in the ENVISION open-label extension study to receive monthly givosiran administration.

“Givosiran is the first GalNAc-conjugate siRNA to achieve positive phase 3 results, and the second example of Alnylam’s R&D strategy bearing fruit due to our focus on genetically validated targets for the advancement of potential high impact medicines,” John Maraganore, PhD, CEO of Alnylam, said in the release. “Assuming favorable regulatory review, we very much look forward to adding givosiran as the second product in our global commercialization efforts.”

Givosiran has received breakthrough therapy from the FDA and prime designation from the European Medicines Agency as well as orphan drug status in the U.S. and EU for the treatment of AHP. The company plans to complete its rolling submission of a new drug application and file a marketing authorization application in mid-2019.