WASHINGTON -- The FDA on Wednesday, the first-ever treatment for treating adults with acute hepatic porphyria, a painful inherited disorder where toxic porphyrin molecules accumulate during heme production.
"This buildup can cause acute attacks, known as porphyria attacks, which can lead to severe pain and paralysis, respiratory failure, seizures and mental status changes. These attacks occur suddenly and can produce permanent neurological damage and death," Richard Pazdur, MD, the FDA's top hematology/oncology official said in a statement.
Reuters reported that drugmaker Alnylam had for a year of treatment.
Approval of the agent — which works by targeting aminolevulinic acid synthase 1 (ALAS1), according to Alnylam — was based on positive results from ENVISION, a multinational phase III study of 94 acute hepatic porphyria patients conducted across 36 centers. In the group randomized to givosiran, porphyria attacks were reduced by 70% (95% CI 60-80%) compared with those given placebo.
Treatment with givosiran also led to similar reductions in urinary aminolevulinic acid and porphobilinogen, as well as in intravenous hemin use.
"Prior to today's approval, treatment options have only provided partial relief from the intense unremitting pain that characterizes these attacks," said Pazdur. "The drug approved today can treat this disease by helping to reduce the number of attacks that disrupt the lives of patients."
Givosiran is the second RNAi drug approved by the FDA, following last year's approval of patisiran (Onpattro) for hereditary transthyretin (hATTR) amyloidosis, which is also manufactured by Alnylam. The RNAi technology underpinning the treatments uses short nucleic acid strings to interrupt gene translation and expression and led to a for the two U.S. geneticists who developed the process.
In ENVISION, nausea and injection site reactions were the most common adverse events (AEs) associated with givosiran, each occurring in greater than 20% of patients. Other AEs that were more frequent compared with the placebo included rash, fatigue, increases in serum creatinine, and elevations of transaminase. One patient treated with the RNAi agent experienced a reversible case of anaphylaxis.