The European Commission has approved cladribine 10-mg tablets (Mavenclad, Merck KGaA) for the treatment of highly active relapsing multiple sclerosis (RMS) as defined by clinical or imaging features, the company has announced.
The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended approval of cladribine for this indication in June, as reported by Medscape Medical News.
Cladribine is an antimetabolite that depletes lymphocytes by causing DNA strand breaks and interfering with DNA synthesis. Cladribine has been shown to reduce the frequency of relapses and to delay disease progression.
Mavenclad is the “first oral short-course treatment to provide efficacy across key measures of disease activity in patients with highly active RMS, including disability progression, annualized relapse rate and magnetic resonance imaging (MRI) activity,” Merck said in a news release.
Approval of cladribine was based on more than 10,000 patient-years of data with over 2700 patients included in the clinical trial program, and up to 10 years of observation in some patients, the company said. Clinical development included three phase 3 trials (CLARITY, CLARITY Extension, and ORACLE MS), the phase 2 ONWARD study, and long-term follow-up data from the 8-year prospective registry known as PREMIERE.
Rocky Road to Approval
“This is an exciting moment and one that will change the way we treat MS,” Gavin Giovannoni, MBBCh, PhD, professor of neurology at Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom, said in the news release.
Cladribine is a “selective immune reconstitution therapy (SIRT) which simplifies treatment administration, by giving patients just two short annual courses of tablets in four years. Patients can benefit from the treatment over a longer period of time without having to continually take medication and without the need for frequent monitoring,” said Dr Giovannoni.
Cladribine for MS has had a rocky road. A new drug application was rejected by European regulators in 2010 and by the US Food and Drug Administration in 2011. The agencies cited concerns about a signal of cancer risk in the initial results of the CLARITY trial.
However, post hoc analysis of CLARITY and CLARITY Extension showed that with cladribine treatment, depending on cumulative dose, up to 90% of patients were free of new lesions on MRI and up to 81% remained relapse-free after 4 years. Especially important for this agent, the analysis raised no long-term safety concerns. The data were presented at the Consortium of Multiple Sclerosis Centers 2017 Annual Meeting in June and were reported by Medscape Medical News.
The most clinically relevant adverse reactions seen in clinical trials were lymphopenia and herpes zoster.
Merck said initial launches of cladribine in Germany and the United Kingdom are expected as early as September, while additional filings for regulatory clearance in the United States and other countries are also planned.
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