Alnylam's RNAi therapeutic Givlaari becomes first treatment approved in US for hepatic porphyria

The FDA said Wednesday that it approved Alnylam Pharmaceuticals' filing for Givlaari (givosiran) to treat adults with acute hepatic porphyria. "Prior to today's approval, treatment options have only provided partial relief from the intense unremitting pain that characterises [porphyria] attacks," commented Richard Pazdur, acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research, adding that the RNAi therapeutic "can treat this disease by helping to reduce the number of attacks that disrupt the lives of patients." 

The injectable therapy, which is dosed based on patient weight, will carry a list price of $575,000 per year, and will be available after discounts for $442,000 per year. Bernstein analysts had modeled Givlaari at a net price in the range of $400,000 to $500,000 annually per patient.

The decision is based on results from the Phase III ENVISION trial of 94 patients with acute hepatic porphyria who received Givlaari or placebo. The study assessed Givlaari's efficacy in terms of rate of porphyria attacks that required hospitalisations, urgent healthcare visits or intravenous infusion of haemin at home. Results showed that the therapy led to a significant 74% mean reduction in composite annualised attack rate, compared to placebo. 

Alnylam said it is in talks with leading payers about value-based agreements for Givlaari and plans to incorporate a new "ultra-rare disease framework" as part of its negotiations. Under the framework, participating government and commercial payers will pay the full value for the treatment "only when it delivers patient outcomes in the real-world setting similar to results demonstrated in clinical trials," the company explained. Moreover, it said an additional prevalence-based adjustment feature will trigger rebates to participating payers "if the number of diagnosed patients they cover exceeds current epidemiologic estimates" for the condition. 

Barry Greene, president of Alnylam, remarked that the company's approach with value-based agreements is intended to act as "insurance for insurers" in a bid to accelerate patient access to treatments "at a sustainable rate to the healthcare system." 

Alnylam has previously estimated that each patient with acute hepatic porphyria costs the healthcare system between $480,000 and $650,000 per year. Meanwhile, Oppenheimer analyst Leland Gershell said "Givlaari will be an entirely new therapy for a poorly treated rare disease patient population," forecasting sales of $47 million next year, and climbing to $560 million at its peak. 

According to Alnylam, Givlaari is expected to be available for shipment to healthcare providers in the US by year-end. Alnylam's other RNAi drug Onpattro (patisiran) was cleared in the US and Europe last year for polyneuropathy due to hereditary transthyretin-mediated amyloidosis.

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