FDA Approves Alnylam’s RNAi treatment for rare diseases
The FDA has given Alnylam a second US approval for one of its RNA interference (RNAi) drugs for acute hepatic porphyria drug Givlaari.
Porphyrias are genetic metabolic disorders caused by an enzyme deficiency in the haem pathway that leads to a build-up of toxic porphyrin molecules in the body, causing attacks that lead to tissue and organ damage.
Hepatic porphyrias is where the deficiency occurs in the liver and – along with painful attacks that often require hospitalisation and treatment with intravenous hemin therapy – can sometimes lead to patients requiring a liver transplant.
Givlaari has been approved on the back of a phase 3 trial – ENVISION – that involved 94 patients with acute hepatic porphyria who received the drug as a once-monthly subcutaneous injection or a matched placebo. Results showed that the therapy reduced the annualised attack rate by 74% compared to control.
RNAi drugs work by switching off genes that aren’t working properly, and Givlaari is only the second drug in the class to be cleared by the FDA.
Givlaari is even more expensive with a list price of $575,000, although Alnylam says that will reduce after discounts to around $442,000 – which is pretty much in line with analyst expectations for a drug with a limited patient population.
Hepatic porphyrias affect around one in 25,000 people in the US, equivalent to approximately 13,000 people, but only around 3,000 patients across the US and Europe are diagnosed and have active disease.
“Porphyria attacks…can lead to severe pain and paralysis, respiratory failure, seizures and mental status changes,” commented Richard Pazdur, head of the FDA’s oncology centre.
“These attacks occur suddenly and can produce permanent neurological damage and death [and] prior to today’s approval, treatment options have only provided partial relief.”
Alnylam has introduced value-based agreements with health insurers that peg the price of Onpattro to how well patients respond to the drug and will adopt a similar strategy with Givlaari.
An added feature for the new drug will be a rebate based on the number of patients treated by a health plan – called a prevalence-based adjustment – in case that number turns out to be higher-than-expected.