Type of information: Granting of a Market Authorisation in the EU
Product name: Mavenclad®
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
- nucleoside analog. Cladribine (2-chlorodeoxyadenosine [2-CdA]) is a purine analog. This synthetic anti-cancer agent that also suppresses the immune system. Cladribine inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA.
Company: Merck KGaA (Germany)
Disease: relapsing-remitting multiple sclerosis
- • On August 25, 2017, Merck KGaA announced that the European Commission has granted marketing authorization for Mavenclad® 10mg (Cladribine Tablets) for the treatment of highly active relapsing multiple sclerosis 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 relapsing multiple sclerosis, including disability progression, annualized relapse rate and magnetic resonance imaging (MRI) activity.
The marketing authorization is based on more than 10,000 patient years of data with over 2,700 patients included in the clinical trial program, and up to 10 years of observation in some patients. The clinical development program included
data from three Phase III trials, CLARITY, CLARITY EXTENSION and ORACLEMS the Phase II ONWARD study and long-term follow-up data from the 8-year prospective registry, PREMIERE. 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 plans additional filings for regulatory approval in other countries, including the United States.
• On June 22, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Mavenclad® for the treatment of relapsing forms of multiple sclerosis. The drug will be available as 10-mg tablets. The benefits with Mavenclad® are its ability to reduce the frequency of relapses and to delay disease
progression. The most important side effects are lymphopenia, which can be severe and long-lasting, and infections, including herpes zoster.
The full indication is: "Treatment of adult patients with highly active relapsing multiple sclerosis (MS) as defined by clinical or imaging features".
- • On July 18, 2016, Merck KGaA announced that the European Medicines Agency (EMA) has accepted for review the Marketing Authorization Application (MAA) of cladribine tablets for the treatment of relapsing-remitting multiple sclerosis. The MAA submission includes data from three Phase III studies, CLARITY, CLARITY EXTENSION and ORACLE MS, and the Phase II ONWARD study. In these trials, Cladribine Tablets showed significantly reduced relapse rates, risk of disability progression and development of new multiple sclerosis lesions, as detected by MRI, versus placebo in patients with relapsing-remitting multiple sclerosis. Together with interim long-term follow-up data from the prospective registry, PREMIERE, the new MAA also includes follow-up consisting of over 10,000 patient years of exposure in total, with follow-up in some patients exceeding eight years.
- • On September 11, 2015, Merck KGaA announced that it intends to submit its investigational treatment cladribine tablets for the treatment of relapsing multiple sclerosis for registration in Europe. The decision follows the company’s evaluation of new data and additional analyses of the compound’s benefit-risk profile. Merck KGaA has submitted a letter of intent to the EMA to file a Marketing Authorization Application (MAA) for Cladribine Tablets, which initiates a process to address a number of pre-submission requirements. The company’s submission plan for other geographies is being further developed and executed. Merck KGaA wound down its clinical development program for Cladribine Tablets in 2011 after some regulatory authorities expressed concerns over the insufficient characterization of the drug's benefit-risk profile. Nevertheless, several large clinical trials were allowed to complete and additional safety information was also collected in a long-term registry.
- • On February 17, 2011, Merck KGaA’s decision to withdraw the application was based on the CHMP's adopted opinion that the data available to date did not allow the Committee to adopt a positive opinion recommending the granting of a marketing authorisation for Movectro®.
• On March 2, 2011, Merck KGaA announced that it received a complete response letter from the FDA on the new drug application (NDA) for Cladribine Tablets, its proprietary investigational oral formulation of cladribine, as a therapy for relapsing-remitting multiple sclerosis. In the complete response letter, the FDA concluded that substantial evidence of Cladribine Tablets’ effectiveness was provided by the CLARITY1 study. However, the FDA has requested Merck KGaA provide an improved understanding of safety risks and the overall benefit-risk profile either through additional analyses or by additional studies. Merck KGaA intends to request an end-of-review meeting with the FDA to clarify next steps and to identify whether data from completed and ongoing clinical studies can address the FDA's questions.
Several clinical studies are still underway (CLARITY [CLAdRIbine Tablets treating MS orallY], ORACLE MS [ORAl CLadribine in Early MS], ONWARD [Oral Cladribine added oN to interferon beta-1a in patients With Active Relapsing Disease]). Top-line results from the CLARITY EXTENSION and ORACLE MS2 studies are expected by the end of 2011. Top-line results from the ONWARD3 study are expected in the first half of 2012.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE: 2011-02-17
UE authorization: 2017-08-24
Favourable opinion UE: 2017-06-22
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: