Biogen and AbbVie’s new multiple sclerosis drug Zinbryta faces fresh prescribing restrictions in Europe after regulators there reviewed liver injuries and one death in patients taking the drug.
The European Medicines Agency launched its review last month, and Friday said it put provisional limits on the medication pending a final decision by the European Commission. Biogen and AbbVie share marketing rights to Zinbryta in the E.U., U.S. and Canada.
Safety worries hit the drug early on—it carries a black-box warning in the U.S.—and the new European move raises a red flag at a crucial time, when tough payers and new challengers, including Roche's Ocrevus, are roiling the MS field.
In the Europe action, regulators are putting up advice and restrictions similar to those noted on the drug's FDA label; as provisional restriction, however, they could be temporary. The EU agency said Zinbryta should be limited to patients with highly active relapsing MS who've failed on other drugs or patients with rapidly evolving relapsing MS with no other options. The agency said Zinbryta should not be used in patients with liver injury or with autoimmune disease beyond MS.
Biogen pointed out Monday that the risk of liver damage with Zinbryta "was known at time of its approval," and "several measures have been taken to manage this risk," including educational materials for doctors and patients. "The benefit-risk profile of Zinbryta remains positive," the company said in an emailed statement.
The FDA black box warns against use in patients with liver problems and advises regular liver testing, including up-front screening before starting the therapy. The drug’s approval is limited to use after patients have failed on one or two prior therapies, or in patients with aggressive disease and no other options.
When Zinbryta was first approved with its severe warning and risk-management program (REMS), analysts expected them to hinder the drug’s launch in the U.S. Though it has been gaining share in some markets in recent months, the new round of safety concerns could ratchet up those worries.
“This drug looks increasingly weak,” commented Bernstein analyst Ronny Gal in a Monday investor note, citing the European regulatory moves.
In January, however, Biogen CEO Michel Vounatsos struck a positive note on the drug’s European launch. “We are encouraged by the launch in Germany, and we expect to receive reimbursement in all major European markets by the end of 2017," Vounatsos said during the company’s fourth-quarter earnings call, and in a first-quarter update noted four straight months of market-share gains in Germany.
Still, some market watchers remain skeptical. The cost-effectiveness watchdog group ICER in March analyzed Zinbryta, and the review committee’s vote wasn’t good. That U.S.-based research organization, the Institute for Clinical and Economic Research, said its expert panel saw no additional benefits from Zinbryta compared with two oral meds, Biogen’s Tecfidera (dimethyl fumarate) and Novartis’ Gilenya (fingolimod).
The committee split on whether it beat Teva’s Copaxone (glatiramer acetate) in its original 20 mg dose—now available as a generic—with those favoring Zinbryta citing a reduced relapse risk and those opposing citing the safety issues and liver monitoring.
Overall, the panel “voted that the drug represents low long-term value for money compared to glatiramer acetate 20 mg, because while the drug is more effective at reducing relapse rates, this improvement was not substantial enough to outweigh the drug's riskier safety profile and increased cost.”
When Zinbryta was approved last year, Leerink analyst Geoffrey Porges pointed to the safety issues as a limiting factor for sales. The drug offers “modest” sales potential, Porges said at the time, forecasting $573 million in sales by 2020.
“The restrictive nature of the label more than supports our cautious view of the drug and its limited potential in the MS therapeutic landscape,” Porges wrote.
As for Ocrevus (ocrelizumab), the new MS challenger? It won kudos from ICER in relapsing MS and progressive MS, too. Though a case of progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal brain disease, cropped up recently in an Ocrevus patient, the drug is still tabbed as one of 2017's top launches. A small number of MS patients on a variety of drugs have developed PML in recent years.
As for the Zinbryta review, Biogen said the "provisional measures" are updates to Zinbryta's official package leaflet and product summary, and are interim moves while the EMA reviews the drug. The agency will issue its final word after its safety review is wrapped up. "Biogen is committed to patient safety and continues to work in full collaboration with the EMA and all relevant regulatory bodies to minimize the risk of hepatic injury in Zinbryta patients," the company said.