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Alnylam Gets Quick FDA OK for Second RNAi Rare Disease Drug

Xconomy Boston — 

[Updated 11/21/19, 10:05 a.m. See below.] An Alnylam Pharmaceuticals drug developed to treat a rare, inherited metabolic disorder won FDA approval on Wednesday, the second regulatory nod the company has received for a drug that turns off a gene to prevent it from causing disease.

The FDA approved the Alynlam (NASDAQ: ALNY) drug givosiran (Givlaari) for acute hepatic porphyria (AHP), a disease caused by a genetic defect that leads to an abnormal accumulation of toxic enzymes that the body otherwise would process and excrete. This enzyme buildup leads to severe neurological attacks and abdominal pain.

Givosiran employs a gene-silencing technique called RNA interference (RNAi). Alnylam says its drug reduces to near-normal levels the toxic enzymes that prompt AHP attacks. The drug’s approval comes 16 months after Alynlam won the FDA nod for patisiran (Onpattro), a treatment for a rare and deadly disease called hereditary transthyretin amyloidosis. That therapy was the first RNAi drug to receive FDA approval. The givosiran approval comes more than two months earlier than expected. The regulator had previously set a Feb. 4, 2020, target date for a decision on the Alnylam drug.

In a prepared statement, Alnylam CEO John Maraganore (pictured above) said givosiran’s approval “reinforces the promise and potential of RNAi therapeutics as a whole new class of medicines.”

Alnylam set a $575,000 annual list price for its new drug. Taking into account rebates and differences in insurance plans, the company says the average net price for givosiran will be $442,000. But the company also says it is working with insurers to hash out “value-based agreements” that peg reimbursement of the drug to how well it works for a patient. Under these agreements, Alnylam says an insurer will be on the hook for the full value of the drug only when a patient sees results similar to what was shown in clinical trials.

The FDA based its decision on results from a Phase 3 study enrolling 94 AHP patients who were randomly assigned to receive monthly injections of the Alnylam drug or a placebo. The main goal was to show a reduction in the frequency of porphyria attacks that required treatment, either at the hospital or at home. The FDA said that on average, patients treated with givosiran in the six-month study experienced 70 percent fewer of these kind of porphyria attacks compared to those given a placebo.

The most common side effects reported included nausea and reactions at the injection site. But the drug had previously sparked more serious concerns about potential toxic effects to the liver. The drug’s label warns that the treatment may cause toxicity to the liver and kidneys, as well as anaphylactic reactions.

[Paragraph added with analyst comment.] In a Thursday research note, SVB Leerink analyst Mani Foroohar wrote that givosiran’s approval for all adult AHP patients is broader than expected; the firm had projected a regulatory nod covering only the most severe cases in which patients experience four or more porphyria attacks per year. Based on the prevalence of the genetic mutation leading to the disease, SVP Leerink calculated these most severe cases translate to 400 patients out of an estimated AHP 4,100 patients in the US, and 600 patients out of 6,400 AHP patients in the European Union. But Foroohar added that Alnylam is projecting more conservative patient totals. The drug’s net price is less than the $480,000 annual cost SVB Leerink estimated, but Foroohar said that the lower price likely reflects the economics of a broader label that allows the drug to be prescribed to more patients.