Hepatic porphyria treatment achieves topline interim results

Alnylam Pharmaceuticals announced positive topline results from an interim analysis of the Envision phase 3 study of givosiran, an RNA interference therapeutic designed to target aminolevulinic acid synthase 1, for the treatment of acute hepatic porphyria, according to a company press release and conference call.

The interim analysis showed that givosiran treatment correlated with a significant reduction in urinary aminolevulinic acid (ALA) levels in patients with acute intermittent porphyria compared with placebo.

“Acute hepatic porphyria is an enormously burdensome disease that affects people – mostly women – in the prime of their lives, and we believe this outcome offers increasing hope for transformative medicine to become available assuming regulatory approval,” John Maraganore, PhD, CEO of Alnylam said during the conference. “Urinary ALA is a biomarker reasonably likely to predict clinical benefit and this outcome suggests that monthly givosiran administration has the potential to significantly reduce the frequency of attacks in these patients.”

Envision phase 3 is an ongoing, international and multicenter study that includes 94 patients with acute hepatic porphyria. The investigators randomly assigned patients to receive either 2.5 mg/kg of givosiran or placebo monthly for 6 months.

Interim results included 43 patients treated for 3 months who achieved the primary endpoint of significant reduction in ALA levels compared with placebo (P < .001). Secondary endpoints will include reductions in acute hepatic porphyria symptoms such as pain, nausea and fatigue.

Regarding safety, the company reported serious adverse events in 22% of patients from the treatment arm and 10% from the placebo arm with no deaths.

According to Maraganore, Alnylam plans to develop the regulatory path forward with the FDA and complete a new drug application by the end of 2018. Additionally, the company expects to report full study results in early 2019.

“While we aren’t able to currently disclose the magnitude of ALA reduction, the very low P value is indicative of a very robust treatment effect,” Maraganore said. “The bottom line is that we believe the overall efficacy and safety profile is fully supportive of our efforts to bring givosiran to patients as rapidly as possible.” – by Talitha Bennett

Reference: www.alnylam.com

Disclosure: Maraganore is an employee of Alnylam.