New EU Restrictions On Biogen’s MS Drug Zinbryta Are ‘Damaging’, Analyst Warns
Executive Summary
Biogen is to continue to work closely with the EMA on clear guidance on how to use its MS drug Zinbryta, after the regulators recommended further restrictions on the product’s use because of the risk of liver damage. But an analyst says the restrictions are detrimental for the drug.
Biogen has committed to working with the European Medicines Agency and all other relevant regulatory bodies to provide clear guidance on the appropriate use of its multiple sclerosis drug, Zinbryta (daclizumab), after the EMA’s pharmacovigilance committee called for further restrictions on the product’s use. An analyst, meanwhile, has warned that the new restrictions will be damaging to Zinbryta’s position in Europe.
The agency’s Pharmacovigilance Risk Assessment Committee in October recommended that because of the risk of serious liver damage, Zinbryta’s use should be restricted to certain patients, with strict liver monitoring.
Specifically, the drug should now only be prescribed for relapsing forms of multiple sclerosis (MS) in patients who have had an inadequate response to at least two disease modifying therapies (DMTs) and cannot be treated with other DMTs, the EMA said on Oct. 27. In addition, doctors should monitor patients’ liver function (ALT, AST and bilirubin) at least once a month as closely as possible before each treatment and continue monitoring them for up to six months after treatments have stopped.
Responding to the PRAC’s recommendation, Biogen told the Pink Sheet that it remained “committed to patient safety.” It said it would “continue to work closely with the EMA and all relevant regulatory bodies to provide patients and healthcare providers clear guidance on the appropriate use of Zinbryta.”
Although the label update “is damaging” for the drug, it “just confirms expectations that Zinbryta is to make little impact within Europe” – Edward Thomason, Datamonitor
“Many patients with MS require multiple medicines throughout the course of their disease,” Biogen noted. “As such, Zinbryta remains an important treatment option for appropriate patients, with a positive benefit-risk profile through adherence to recommended risk-minimization measures.” The company manufactures five other MS drugs, including Tecfidera (dimethyl fumarate) and Avonex (interferon beta-1a). Zinbryta, which was authorized in the EU in July 2016, is co-promoted by Biogen and AbbVie.
Unpredictable And Potentially Fatal Injury
The PRAC’s recommendation follows a review of Zinbryta’s effects on the liver at the request of the European Commission under an Article 20 referral.
The review, which began on June 9, found that unpredictable and potentially fatal immune-mediated liver injury can occur during treatment with the drug and for up to six months after stopping treatment. Clinical trials had shown that 1.7% of patients receiving Zinbryta had a serious liver reaction.
The latest recommendations follow provisional measures that the PRAC issued in July this year to minimize the risk of liver injury. At that time the EMA said it was provisionally restricting Zinbryta’s use to patients with highly active relapsing disease that had failed to respond to certain other treatment, and to patients with rapidly evolving relapsing disease who cannot be treated with other medicines.
Damaging For Zinbryta
Commenting on the extended restrictions on Zinbryta’s label, Datamonitor analyst Edward Thomason warned they would be detrimental to Zinbryta’s position in Europe. “They will limit use as a last resort disease-modifying therapy in third or later lines of therapy and require dose monitoring before each treatment and up to six months after treatment has stopped,” he said.
Although the label update is “damaging” for the drug, it “just confirms expectations that Zinbryta is to make little impact within Europe,” Thomason added. “In July 2017, the EMA had already imposed provisional restrictions on Zinbryta’s use. Furthermore, the success of new disease-modifying therapies in MS, such as Tecfidera, has already reduced Zinbryta’s target later line patient populations. The impending approval of Genentech’s Ocrevus (ocrelizumab) in Europe was only going to intensify this effect.”
The recommendations from the PRAC’s review will now be sent to the EMA’s human medicines scientific committee, the CHMP, which will adopt the agency’s final opinion. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU member states.
Biogen said it could not speculate on how the ongoing Article 20 procedure would impact the decisions of regulatory bodies outside of the EU.
Thomason noted that in the US, Zinbryta is approved with a black-box that warns prescribers and patients about hepatic injury risks including autoimmune hepatitis and liver failure and other immune-mediated disorders.
“In the US, Zinbryta’s safety concerns and its minimal improvement over Avonex has already resulted in Zinbryta being positioned as a third-line therapy for highly active relapsing-remitting MS, where it has made little impact,” he said.
“Although the Food and Drug Administration’s label is less restrictive, Zinbryta will still be unable to match Tysabri’s commercial success,” Thomason continued. “The limited impact of Zinbryta weakens Biogen’s position in MS, having trusted that Zinbryta’s as impressive clinical efficacy as Tysabri would have been enough to defend its market share as patients shifted towards high-efficacy rivals Ocrevus and Sanofi Genzyme’s Lemtrada (alemtuzumab). Biogen now hopes Tecfidera’s strong efficacy, best-in-class tolerability and convenient oral formulation would be enough to defend its market leading position in MS.”
From the editors of Scrip Regulatory Affairs.