4:08 PM
Apr 12, 2019
 |  BC Extra  |  Clinical News

Alnylam's givosiran reduces mean porphyria attacks by 74% in Phase III

Alnylam reported detailed data Friday showing that givosiran reduced the mean attack rate in acute hepatic porphyria patients by 74% in the Phase III ENVISION trial. The company reaffirmed its plans to complete submission of a rolling NDA to FDA and submit an MAA to EMA for givosiran mid-year, but said it could not speculate on any potential postapproval monitoring requirements for the therapy in light of the higher adverse event rates, including chronic kidney disease and elevated liver transaminase levels, that were seen in the treatment arm of the trial.

Acute hepatic porphyrias are a family of rare genetic diseases resulting in enzyme deficiency of the heme biosynthesis pathway in the liver. Givosiran is a subcutaneous RNAi therapeutic targeting aminolevulinate synthase-1 (ALAS-1).

On ENVISION's primary endpoint, Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) said givosiran significantly reduced the annualized rate of composite porphyria attacks requiring hospitalization, urgent healthcare visit or hemin administration over the six-month treatment period by a mean of 74% and median of 90% vs. placebo. The company also said that 50% of givosiran-treated patients were attack free during the treatment period vs. 16.3% of placebo patients.

President of R&D Akshay Vaishnaw told BioCentury that patients with acute hepatic porphyria can experience 10 to 20 attacks per year, and that there are no approved standard of care approaches to treat these attacks. While some physicians may use IV hemin treatment, he noted that hemin can cause damage to veins and the liver and is not very effective.

On the safety front, Alnylam said last month that givosiran led to higher rates of serious adverse events (20.8% vs. 8.7%), chronic kidney disease (10.4% vs. 0%) and liver transaminase increases of greater than three times the upper limit of normal (14.6% vs. 2.2%) compared with placebo. At baseline, patients already had iron overload or liver disease and some degree of renal impairment.

Alnylam said that on exploratory measures givosiran also led to a greater proportion of patients with an improvement in overall health status, an overall higher level of treatment satisfaction and an increased ability to perform activities of daily living vs. placebo. The double-blind, international trial enrolled 94 patients ages 12 and older who experienced at least two porphyria attacks within the prior six months to receive placebo or once-monthly subcutaneous 2.5 mg/kg givosiran.

Alnylam said last month that givosiran met ENVISION's primary endpoint, but did not disclose detailed data. The new data will be presented April 13 at the European Association for the Study of the Liver (EASL) meeting in Vienna (see "Alnylam's Rare Liver Disease RNAi Meets in Phase III").

Givosiran has Orphan Drug designation in the U.S. and EU, breakthrough therapy in the U.S. and PRIority MEdicines (PRIME) designation in the EU.

Alnylam gained $1.71 to $89.81 on Friday. It announced the additional data after market close.

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