Dive Brief:

• The Food and Drug Administration on Tuesday flagged a label update made last month to Novartis' Gilenya, explaining patients' multiple sclerosis can get "much worse" when they stop taking the oral medication.
• Regulators identified 35 cases where patients experienced severely increased disability two to 24 weeks after going off Gilenya. They said these cases were more severe than typical multiple sclerosis relapses, and that "several patients who were able to walk without assistance prior to discontinuing Gilenya progressed to needing wheelchairs or becoming totally bedbound."
• Novartis noted in an email to BioPharma Dive that the label update isn't a blackbox warning nor a contraindication. Additionally, Gilenya's label in Europe underwent a similar update in January that "has not impacted prescribing behavior," according to a company spokesperson.

Dive Insight:

Novartis maintains that the benefits of Gilenya (fingolimod) far outweigh the potential downsides — especially since the label addition pertains to when people stopped taking the drug.

The company spokesperson in his email to BioPharma Dive said more than 100,000 patients in the U.S. have received Gilenya. He also highlighted how the label update wasn't due to unexpected events. "In fact, many of them have already been published in scientific publications," he said.

What's more, "similar cases have been described in the literature for other MS therapies, such as natalizumab," the spokesperson wrote.

In its drug safety communication, the FDA advised healthcare professionals to inform patients before starting with Gilenya of the potential risk of severe increases in disability after ceasing treatment with the drug. 

Patients should be observed closely treatment is stopped for any subsequent exacerbation of their disease, the FDA said. 

Gilenya is Novartis' top-selling product, fetching net sales of $818 million in the third quarter and more than $2.5 billion over the first nine months of 2018. Though first approved in 2010, the drug continues to achieve modest growth even amid fierce competition from rival therapies like Biogen's Tecfidera (dimethyl fumarate), Teva Pharmaceuticals' Copaxone (glatiramer acetate) and Roche's recently approved Ocrevus (ocrelizumab).

The franchise still faces challenges, however.

Generics makers, for instance, are looking to get in on the Gilenya revenue by bringing copycat versions to market. Though a recent inter partes review upheld the validity of a dosing patent that would in theory extend Gilenya's exclusivity to December 2027, other legal battles could bring a patent cliff as early as 2022.

"We have filed the lawsuits against the relevant parties. We're waiting now the next steps with respect to the various court cases and what these various parties might do. As soon as we have any further update, of course, we’ll keep you all aware," Novartis CEO Vas Narasimhan said to investors in October on the company's third quarter earnings call.

Gilenya works by regulating an immune protein known as sphingosine 1-phosphate receptor. Siponimod, an investigational multiple sclerosis therapy that Novartis last month filed for approval, also targets this receptor.

The company spokesperson said siponimod "is a different molecule with different [pharmacokinetic] properties and receptor affinities."

"It was studied mainly in [secondary progressive multiple sclerosis] — in which the pattern of focal inflammatory activity is different (lower) from the earlier [relapsing multiple sclerosis] patients — and based on the available dataset has not shown such a signal."