Merck KGaA is celebrating a green light from the EU Committee for Medicinal Products for Human Use (CHMP) for cladribine, its oral multiple sclerosis therapy, seven years after being turned down by the panel.
The CHMP issued a positive opinion for oral cladribine, which if approved will be sold as Mavenclad, for the treatment of patients with relapsing-remitting MS who have high disease activity.
It’s a remarkable comeback for the drug, which was rejected by the CHMP in 2010 and abandoned by Merck in 2011 – despite picking up some approvals in markets such as Australia and Russia – on the back of feedback from regulatory authorities including the FDA and EMA.
At the time Merck said it would have to embark on a new clinical trials programme that would take several years to complete, which it was unprepared to do given the “competitive landscape” – with oral therapies such as Novartis’ Gilenya (fingolimod) and Biogen’s Tecfidera (dimethyl glutamate) reaching or near the market.
After taking another look at the data in 2015 however Merck decided to re-file the drug in the EU with a new risk-benefit analysis, and recently listed it among a clutch of new products that it expects to generate annual revenues of around €2bn by 2022, although the bulk of that is expected to come from Pfizer-partnered immuno-oncology drug Bavencio (avelumab).
“The positive opinion from the CHMP is an extraordinary development for Merck, affirming our belief in cladribine tablets as a potential important treatment option for patients living with MS,” said Belén Garijo, chief executive of Merck’s healthcare division.
Armed with EU backing Merck has also suggested that it may discuss the possibility of a marketing application for oral cladribine in the US, as well as looking again at other markets such as Australia, Russia, and Canada.
The company said the CHMP positive opinion is based on more than 10,000 patient years of data with over 2,700 patients included in the clinical trial programme, as well as more than 10 years of observation in some patients.
In trials, patients with high disease activity saw a 67% reduction in annual relapse rate over two years compared to placebo, while the risk of disability progression lowered by 82%. Follow-up studies also revealed that oral cladribine could be stopped in year three and four without an increase in relapses.
Mavenclad will launch into a market where Tecfidera is currently dominating with sales of around $4bn last year, with Gilenya bringing in another $3.1bn for Novartis and another oral drug from Sanofi – Aubagio (teriflunomide) – trailing in third but growing strongly with sales of €1.3bn.
Merck hasn’t given any indication of its sales expectations for Mavenclad, but recently said analyst consensus estimates for EU sales were in the €200m-€400m range.
The company thinks oral cladribine has a key differentiator from its rivals, which require daily dosing. Cladribine is given for five consecutive days over two months – i.e. to days’ treatment in total – with another 10-day course over two months a year later. Given trials indicate that regimen provides four years’ cover, Merck thinks that could be “highly attractive to patients”.
The CHMP’s recommendation will be referred to the EMA, which is expected to make a final decision on the Mavenclad within 67 days.