Alnylam's Innovative RNAi Therapeutic Givlaari Receives FDA Approval for Acute Hepatic Porphyria

VCBeat (WeChat ID: vcbeat) learned from foreign media that on November 20, 2019, local time, Alnylam Pharmaceuticals, a biopharmaceutical company headquartered in Cambridge, Massachusetts, USA, announced that its innovative drug Givlaari (givosiran), developed based on RNAi technology, had received FDA approval for marketing to treat acute hepatic porphyria (AHP) in adults.

It is reported that Givlaari was approved just four months after the submission of its New Drug Application (NDA) to the FDA, nearly three months ahead of schedule. This approval makes it the second RNAi therapeutic globally to receive FDA approval for Alnylam Pharmaceuticals within the past 16 months, as well as the first and only FDA-approved treatment for acute hepatic porphyria (AHP).

Prior to its approval, Givlaari had already been granted “Breakthrough Therapy” and “Orphan Drug” designations by the FDA. Meanwhile, the drug is currently undergoing accelerated assessment by the European Medicines Agency (EMA), which has also awarded it “PRIME” (PRIority MEdicines) and “Orphan Drug” status.

Acute Hepatic Porphyria (AHP) is a rare genetic disorder caused by genetic defects, leading to the accumulation of neurotoxic heme intermediates, aminolevulinic acid (ALA) and porphobilinogen (PBG), which in turn result in long-term complications such as chronic neuropathic pain, hypertension, chronic kidney disease, and liver disease. Givlaari, a subcutaneously administered RNAi therapy targeting aminolevulinic acid synthase 1 (ALAS1), reduces ALA and PBG levels in patients to normal ranges through once-monthly dosing, thereby reducing incidence rates, controlling chronic symptoms, and alleviating disease burden.

This approval is based on the positive results from the Phase III ENVISION clinical trial of the drug. In this six-month, randomized, controlled trial, 94 patients with acute hepatic porphyria (AHP) received monthly subcutaneous injections of Givlaari (2.5 mg/kg) or placebo. The study results demonstrated a 74% reduction in the rate of disease attacks among patients treated with Givlaari compared with those receiving placebo.

“We believe that the approval of Givlaari represents another milestone in the field of precision genetic medicine, offering new hope to patients with AHP and providing healthcare professionals with a new treatment option,” said John Maraganore, CEO of Alnylam. “We are grateful to all the researchers, trial participants, and their families who contributed to the development of Givlaari, and we also appreciate the FDA’s rapid approval of this new therapy.”

Alnylam Pharmaceuticals, a pioneer in the development of RNAi therapies and the world’s first developer of an RNAi-based drug, saw its product Onpattro (patisiran) approved by the United States and the European Union in 2018. This marked the world’s first approved RNAi therapeutic, indicated for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary ATTR (hATTR) amyloidosis.

Unlike Onpattro, which utilizes lipid nanoparticle delivery technology, the newly approved Givlaari is an RNAi therapeutic developed based on enhanced stability chemistry (ESC) GalNAc conjugation technology. This technology enables subcutaneous administration with highly durable efficacy and a broad therapeutic index. Notably, this approval marks the first global regulatory endorsement of ESC GalNAc conjugation technology.

It is reported that the new drug Givlaari is currently priced at $39,000 per vial, with Alnylam Pharmaceuticals estimating an annual cost of approximately $440,000 per patient. However, the company also stated that it will offer “prevalence-based adjustments” in the future, meaning the drug’s price will be adjusted if the number of patients exceeds expectations.

(Compiled by Hu Lushuang)