VIDEO: Acute intermittent porphyria therapeutic progresses to phase 3

SAN FRANCISCO — In this exclusive video perspective from The Liver Meeting 2018, Karl E. Anderson, MD, from the University of Texas Medical Branch, discusses positive phase 1/2 results for givosiran, an investigational RNAi therapeutic for patients with acute intermittent porphyria.

“We found that it had a long duration of affect, of at least a month, so it can be given monthly,” Anderson told Healio Gastroenterology and Liver Disease. “It was effective in downregulating urinary [aminolevulinic acid (ALA)] and [porphobilinogen (PBG)].”

As of February 2018, monthly dosing achieved approximately 60% to 70% aminolevulinic acid synthase 1 (ALAS1) mRNA silencing. Results from up to 22 months of treatment in an open-label extension of the study including continuous dosing of 2.5 mg/kg per month led to enhanced clinical activity with ALA and PBG lowered by more than 80%.

According to Anderson, the safety profile was good with one patient who died of acute pancreatitis that was considered unrelated to study drug as there was evidence of gallstone disease.

A larger phase 3 study is underway with complete enrollment of 94 patients. The phase 3 study is being conducted in 36 centers in 18 countries.

“Initial results should be available in early 2019 and applications for approval in the U.S. and Europe will be submitted in 2018 and 2019,” Anderson said.

Reference:

Anderson KE, et al. Abstract 0079. Presented at: The Liver Meeting 2018; Nov. 9-13, 2018; San Francisco.

Disclosure: Anderson reports he has financial connections with Alnylam Pharmaceuticals, Mitsubishi Tanabe Pharma and Recordati Rare Diseases.