- First oral short-course treatment for highly active relapsing multiple sclerosis (RMS) now approved in Europe
- Mavenclad has shown sustained clinical efficacy for up to 4 years with a maximum of 20 days of oral treatment over 2 years
- Marketing authorization includes the 28 countries of the European Union (EU), with first launches in the UK and in Germany
Darmstadt, Germany, 25 August, 2017 – Merck KGaA, Darmstadt, Germany, a leading science and technology company, today announced that the European Commission (EC) has granted marketing authorization for MAVENCLAD® 10mg (Cladribine Tablets) for the treatment of highly active relapsing multiple sclerosis* (RMS)^1^ in the 28 countries of the European Union (EU) in addition to Norway, Liechtenstein and Iceland. 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.
“Multiple Sclerosis (MS) is one of the world’s most common neurological disorders. With the approval of MAVENCLAD® in the European Union, we are pleased to offer patients and clinicians an innovative agent with a simplified dosing schedule as a new approach to managing active relapsing MS,” said Belén Garijo, CEO Healthcare and Member of the Executive Board of Merck KGaA, Darmstadt, Germany. ”This is a pivotal change in the treatment of MS which further demonstrates our unwavering commitment to advancing patient care.”
MAVENCLAD®’s marketing authorization is based on more than 10,000 patient years of data with over 2,700 patients included in the clinical trial program,^2^
and up to 10 years of observation in some patients. The clinical development program included data from three Phase III trials, CLARITY, ^3^,^4^ CLARITY EXTENSION^5^ and ORACLE MS,^6^ the Phase II ONWARD study;^7^ and long-term follow-up data from the 8-year prospective registry, PREMIERE.^8^ The efficacy and safety results of these studies allowed for a full characterization of the benefit-to-risk profile of MAVENCLAD®.
“This is an exciting moment and one that will change the way we treat MS,” said Gavin Giovannoni, Professor of Neurology at Barts and The London School of Medicine and Dentistry, Queen Mary University of London. “MAVENCLAD® 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.”
The authorization follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) that was received in June 2017. MAVENCLAD® is expected to become commercially available to patients in Europe by prescription within the coming months, with initial launches in Germany and UK expected as early as September 2017. In addition, Merck KGaA, Darmstadt, Germany plans additional filings for regulatory approval in other countries, including the United States.
“Multiple Sclerosis affects more than 700,000 people across Europe and has no cure to date,” said Anne Winslow, President of the European Multiple Sclerosis Platform. ”New treatment options will significantly help improve the quality of life of people living with active relapsing MS.”
In patients with high disease activity, post hoc analyses of the two-year Phase III CLARITY trial^2^,^3^ demonstrated that MAVENCLAD® reduced the annualized relapse rate by 67% and the risk of 6-month confirmed EDSS progression by 82% versus placebo. As demonstrated in the Phase III CLARITY EXTENSION^5^ study, no further MAVENCLAD® treatment was required in Years 3 and 4. The comprehensive dataset has informed the posology and monitoring requirements. The most clinically relevant adverse reactions were lymphopenia and herpes zoster. Lymphocyte counts must be assessed before, and during, treatment with MAVENCLAD®. MAVENCLAD® is contraindicated in certain groups including immunocompromised patients and pregnant women.
For MAVENCLAD® prescribing information, please visit http://www.ema.europa.eu/ema/.
* Defined as: patients with 1 relapse during the previous year and ≥ 1 T1 Gd+ lesion or ≥ 9 T2 lesions while on therapy with other DMDs; OR patients with ≥ 2 or more relapses in the previous year, whether on DMD treatment or not.
^1^ MAVENCLAD® Summary of Product Characteristics August 2017
^2^ Merck KGaA, Darmstadt, Germany data on file
^3^ Giovannoni G, Comi G, Cook S et al. A Placebo-Controlled Trial of Oral Cladribine for Relapsing Multiple Sclerosis. 2010 New England Journal of Medicine 362:416-426
^4^ Giovannoni G et al. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis Lancet Neurol 2011; 10:329–337
^5^ EU Clinical Trials Register. A Phase IIIb, Double-Blind, Placebo-Controlled, Multicenter, Parallel Group, Extension Trial to Evaluate the Safety and Tolerability of Oral Cladribine in Subjects with Relapsing-Remitting Multiple Sclerosis Who Have Completed Trial 25643 (CLARITY). Available at https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-000381-20/results. Last accessed August 2017
^6^ Leist T, Comi G, Cree B et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol 2014; 13: 257–67
^7^ EU Clinical Trials Register. A phase II, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability and efficacy study of add-on Cladribine tablet therapy with Rebif New Formulation in Multiple Sclerosis Subjects with Active Disease. Available at https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-003366-33/results. Last accessed August 2017
^8^ Schreiner T, Miravalle A,. Current and Emerging Therapies for the Treatment of Multiple Sclerosis: Focus on Cladribine. Journal of Central Nervous System Disease. 2012; 4: 1–14