Gilenya vs. Cladribine: Differences and similarities in regulatory review

Pharmawire covered our comment, see below:

Novartis: Recent Gilenya decision best-case scenario; cladribine receives two-year label restriction in Australia - physicians Pharmawire

Novartis' (NYSE:NVS) Gilenya is expected to take more market share than previously expected in multiple sclerosis, due to labeling that was a "best case scenario" for the company, neurologists said. Gilenya (fingolimod) 0.5 mg daily received approval today, making it the first oral multiple sclerosis drug approved in the US. Competitor Merck-Serono is awaiting an FDA ruling on their competing oral compound cladribine, later this year. Under the label restriction in Australia, Merck-Serono's Movectro (cladribine) is indicated for the treatment of relapsing-remitting multiple sclerosis for a maximum duration of two years. Elmar SchNee, Head of Pharma at Merck KGa, said at a recent investor conference that cladribine faces an upcoming EU decision, and the regulators might be "more restrictive" there, following on from comments about the recent 2-year Australian label restriction. Cladribine tablets will be registered in Australia under the trade name Movectro. "I am extremely pleased Gilenya got approved, and pleased that the FDA didn’t put a lot of restrictions on it, as those decisions are best left to physicians," said Dr Anne Cross, a professor of neurology at the Manny and Rosalyn Rosenthal – Dr. John Trotter MS Chair in Neuroimmunology at Washington University in St. Louis. Cross said she will initially use Gilenya in patients who have failed the front-line therapies, but expects to use the drug in other patients after the drug has been on the market for awhile. "I'm a conservative person, so I tend to not use new drugs in a lot of patients until after a few months," she said. However, while Cross is excited about the potential of cladribine due to its more convenient dosing schedule relative to Gilenya, she said the drug is "a problem if you need to reverse it." She explained that cladribine is long acting, therefore if patients develop infections, "you’re in a bind. It isn’t reversible. That worries me a little bit about cladribine, moreso than Gilenya," Cross said. There are some individual things that will be “ironed out” with Novartis' drug, such as how closely to monitor heart rate, but this issue should “sort itself out over time,” Cross noted. "There is a lot of demand for Gilenya. Novartis really got a deal from the regulators. It’s going to do a lot for their market share," said Dr Samuel Hunter, a neurologist and President of the Advanced Neurosciences Institute in Franklin, Tennessee. He added that he was surprised that the drug did not receive a blackbox warning due to several malignancies that were observed in clinical trials. Still, Gilenya was likely spared such a warning since while there was an increased risk for the development of malignancies in the Phase II TRANSFORMS study, which tested the 0.5 mg and 1.25mg doses of Gilenya, in the larger Phase III trial, involving over 1,000 patients, there was no increased risk, noted Dr Douglas Jeffery, a neurologist at Wake Forest University School of Medicine. In addition, there was also no increase in cancer risk in patients who entered into the long term extension study, he said. There is a risk management program, and both the company and physicians will continue to evaluate the safety of Gilenya, Jeffery noted. Jeffrey also cautioned that despite Novartis' seemingly easy approval process and label for their oral MS drug, Merck-Serono's cladribine and its side-effects are at a different order of magnitude in regards to malignancy risk. Based on the literature in hairy cell leukemia, patients who received lower doses of cladribine than those used in MS trials, reported secondary malignancies. "This is a whole different order of magnitude, which the FDA will have to look at very carefully," he said. Hunter added that despite the ease for Novartis in securing approval, he also believes that the FDA will follow guidelines from the EU and Australian regulators with regards to cladribine and its label restriction. "The agency is going to be cautious, since the drug is too similar to other immunomodulators that have had problems in MS," he said, referring to Biogen’s Tysabri. However, a risk management program is easier to follow for an oral drug, he noted. The risk management plan for Gilenya is very benign, said Hunter, who has the in-house skills to handle those tests internally at his clinic. "We have a retinal scanner that can do the job for the eye test. Most neurologists have an EKG machine. That’s manageable for most people who are treating MS," he said. The risk management program for Gilenya requires that patients receive a medication guide, and a letter and safety information guide for healthcare providers. Novartis will also be initiating a five-year, international post-authorization safety study to monitor selected safety-related outcomes and a voluntary pregnancy registry. Dr Daniel Kantor, a neurologist and Medical Director of the Neurologique Foundation in Florida, said the label for Gilenya was the best possible outcome for Novartis. The addition of an indication for disability is probably the most important indication for MS in a long-time, he said. That combined with the fact that it is an oral drug for delaying disability progression is sure to increase market share, he noted. The REMS program for Gilenya was also very beneficial to Novartis, and will be clarified further in the upcoming weeks, Kantor said. by Kimberly Ha

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org