Biogen and AbbVie said today they are voluntarily withdrawing Zinbryta® (daclizumab) from the market worldwide. The withdrawal came as the European Medicines Agency started an “urgent review” of the relapsing multiple sclerosis (MS) treatment under its Article 20 referral procedure following seven cases of serious inflammatory brain disorders in Germany—including encephalitis and meningoencephalitis—and one case in Spain.
The companies also told the EMA today that they will stop ongoing clinical studies with Zinbryta in the EU.
“Given the nature and complexity of adverse events being reported, characterizing the evolving benefit/risk profile of Zinbryta will not be possible going forward given the limited number of patients being treated,” Biogen and AbbVie said in a statement. “Therefore, Biogen and AbbVie believe it is in the best interest of patients to voluntarily withdraw worldwide marketing authorizations for Zinbryta.”
Added Alfred Sandrock, M.D., Ph.D., EVP and CMO at Biogen: “Biogen and AbbVie continue to prioritize patient safety and the care of multiple sclerosis patients worldwide.”
“Biogen believes the voluntary worldwide withdrawal of Zinbryta, a treatment for relapsing multiple sclerosis, is in the best interest of patients,” Dr. Sandrock said.
Zinbryta is an interleukin-2 receptor-blocking antibody indicated for the treatment of adults with relapsing forms of MS. The once-monthly self-administered, subcutaneous treatment was approved by the European Commission in July 2016, three months after the drug won FDA approval.
The U.S. prescribing label for Zinbryta states that because of the drug’s safety profile, “the use of Zinbryta should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.”
That safety profile includes black box warnings that Zinbryta can cause skin reactions and severe liver injury, including autoimmune hepatitis and liver failure—and can increase the risk of immune-mediated disorders, including autoimmune disorders such as autoimmune hepatitis. Because of those risks, Zinbryta is available only through a restricted Risk Evaluation and Mitigation Strategy program.
Zinbryta generated $53 million in revenues for Biogen last year—a far cry from the peak $500 million in annual sales predicted for the drug when it reached the market two years ago.
Zinbryta generated the lowest revenues among seven Biogen treatments in its anchor therapeutic area of MS. The company’s best-selling MS treatment Tecfidera® (dimethyl fumarate), by comparison, racked up $4.214 billion in revenues.
While Biogen seeks to broaden its portfolio beyond MS, the company’s late-stage Alzheimer’s candidate aducanumab (BIIB037), being codeveloped with Eisai, was at the center of a stock selloff February 14 after Dr. Sandrock disclosed that Biogen made mid-study changes to a pair of Phase III trials, for which data is expected next year.
On November 9, the EMA announced further restrictions to the approved use of Zinbryta intended to reduce the risk of serious liver damage in patients. The EMA directed what the U.S. guidelines suggested. Zinbryta should be used only in patients showing inadequate response to at least two disease-modifying therapies for MS, and who cannot be treated with another therapy.
Those restrictions followed a review conducted by the agency’s Pharmacovigilance Risk Assessment Committee (PRAC), which issued recommendations in October 2017. The Committee for Medicinal Products for Human Use (CHMP) adopted EMA’s final opinion, adopted by the European Commission.
Biogen cited that review in January when it announced impairments to GAAP net income of $84 million and GAAP EPS of 39 cents a share attributed to the 2017 EMA review. The company also disclosed a series of charges, including:
- A GAAP tax charge of $42 million, and a non-GAAP tax charge of $50 million, related to the impairment of Zinbryta-related tax assets. Non-GAAP net income and EPS were negatively impacted by $61 million and $0.29, respectively.
- A $31.2 million pretax impairment charge related to intangible assets, namely acquired and in-licensed rights and patents.
- An approximately $20 million charge related to Zinbryta assets, including inventory.
AbbVie also recorded impairment charges last year related to Zinbryta. According to AbbVie’s Form 10-K annual report for 2017, the company took an impairment charge of $354 million that reduced both the gross carrying amount and net carrying amount of the underlying intangible assets “due to lower expected future cash flows for the product.”
AbbVie also recorded a $39 million impairment charge in 2016 related to its U.S. product rights “due to a decline in the market for the product.”
In addition to the U.S. and EU, Zinbryta has been approved in Australia, Canada, and Switzerland. According to the EMA, more than 8000 patients to date have been treated with Zinbryta worldwide, with the majority of EU patients having been treated in Germany.