- The Food and Drug Administration on Wednesday approved Alnylam Pharmaceuticals' Givlaari, a treatment for the inherited disease acute hepatic porphyria. The regulator's decision came about three and a half months early and followed another early OK for Novartis' sickle cell drug Adakveo, which had been scheduled for a decision in January.
- Givlaari injections reduced the number of porphyria attacks by 70% in patients with the rare condition when compared to those who were given placebo in clinical trials, the FDA said.
- Alnylam set a price that it estimated would yield an average per-patient cost of $575,000 a year, which after discounts and rebates would be effectively $442,000. The biotech also said it would offer payers bigger rebates if the number of diagnosed patients exceed epidemiological estimates.
Patients with acute hepatic porphyria experience attacks that can include pain, respiratory failure, paralysis and seizures. Patients undergoing an attack must go to a hospital or clinic to receive infusions of hemin, which suppresses the protein ALAS1. Excessive amounts of ALAS1 trigger the buildup of porphyrin in patients' tissues.
Givlaari (givosiran) is injected preventively once a month, and works by blocking messenger RNA from encoding production of ALAS1.
While the mutation that can result in the condition is fairly common, the number of people who have active disease is small. Alnylam estimates 6,000 patients in the U.S. and European Union, with 3,000 of them diagnosed — split equally between the two regions. About 1,000 suffer four or more attacks a year, the company said.
Because of the price and uncertainty over the number of patients, Alnylam will be offering what it calls a "prevalence based adjustment," a rebate that will kick in if the numbers are greater than expected. In return, Alnylam will ask that insurers cover Givlaari based on the FDA label and not based on clinical trial enrollment criteria.
Its estimated annual per-patient cost of $442,000 incorporates its assumptions that the prevalence-based adjustment will be applied in some cases.
Givlaari will be commercially available within weeks, Alnylam said.
Givlaari is the second RNA-interfering agent for which Alnylam has gained approval. Onpattro (patisiran) is in a tough competition with Pfizer's Vyndaqel (tafamidis) and Akcea Therapeutics' Tegsedi (inotersen) in patients with ATTR amyloidosis.
Its clearance by the FDA is also notable for the speed at which the agency reached its decision. In addition to Givlaari and the quickly reviewed Adakveo, the FDA has in recent weeks approved drugs from Vertex and Chinese biotech Beigene ahead of schedule.