FDA Approves MAVENCLAD (Cladribine) Tablets as First and Only Short-Course Oral Treatment for Relapsing-Remitting and A

- MAVENCLAD is the first oral MS treatment to provide two years of proven efficacy with a maximum of 20 days of treatment

- MAVENCLAD's unique mechanism may provide an important new option for patients with ongoing active disease

- MAVENCLAD demonstrated significant efficacy across key measures of disease activity

- Approval is based on clinical program consisting of more than 9,500 patient years of cladribine data and up to 8 years of time on study

DARMSTADT, Germany, March 29, 2019 /PRNewswire/ --

Not intended for U.S. or U.K. based media

Merck, a leading science and technology company, today announced that the U.S. Food and Drug Administration (FDA) has approved MAVENCLAD() (cladribine) tablets for the treatment of adults with relapsing-remitting disease (RRMS) and active secondary progressive disease (SPMS). MAVENCLAD is the first and only FDA approved treatment for RRMS and active SPMS that provides two years of proven efficacy with a maximum of 20 days of oral treatment, during a two-year period.

Because of its safety profile, use of MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of multiple sclerosis (MS), and MAVENCLAD is not recommended for use in patients for Clinically Isolated Syndrome (CIS). The MAVENCLAD label includes a boxed warning for potential risk of malignancy, and the risk of teratogenicity. The label appropriately defines the relevant associated contraindications.

"Multiple sclerosis is the leading cause of non-traumatic disability in young and middle-aged adults," said Belén Garijo, CEO Healthcare and Member of the Executive Board of Merck. "We feel privileged to introduce MAVENCLAD into clinical practice in the United States. MAVENCLAD opens a new way to treat MS--a treatment that requires a maximum of 20 days of oral therapy to deliver two years of efficacy to a patient. This approval is a testimony to our long-standing commitment to people living with MS."

"As an investigator in the clinical trial program, I am pleased MAVENCLAD will now be available to patients in the US. With short treatment courses with pills taken for no more than 10 days in a year and no injections or infusions, MAVENCLAD is an efficacious new treatment option for MS," said Thomas Leist, M.D., PhD, Director, Comprehensive Multiple Sclerosis Center at Jefferson University Hospitals, Philadelphia, USA. "Nearly 1 million individuals are afflicted with MS in the US alone according to a recent National MS Society sponsored study. MAVENCLAD is a welcome new oral treatment option for this heterogenous and often unpredictable disease."

Eighty--five percent of people living with MS are initially diagnosed with RRMS, characterized by attacks of new or increasing neurological symptoms. Most people with RRMS will eventually transition to a secondary progressive course in which there is a progressive worsening of neurologic function over time.(1 )SPMS can be further characterized at different points as either active (with relapses and/or evidence of new MRI activity) or not active.

"The FDA approval of MAVENCLAD is excellent news for people living with RRMS and active SPMS. MAVENCLAD offers a new and effective option for some of those patients with an oral dosing schedule unlike any other treatment currently available," said June Halper, CEO of the Consortium of MS Centers. "People living with MS should have the ability to work with their clinician to choose a treatment with a dosing schedule that supports their lifestyle. CMSC congratulates Merck for their dedication to bring MAVENCLAD to the US as the first short-course oral treatment option for the community."

In the clinical trial program, 1,976 patients received therapy for a total of 9,509 patient years, of which the mean time on study including follow-up was approximately 4.8 years and 24% of the follow-up was for eight years. MAVENCLAD demonstrated clinical efficacy across key measures of disease activity, such as annualized relapse rate, disability progression, and magnetic resonance imaging (MRI) activity:

-- Patients experienced a 58% relative reduction in the annualized relapse rate with MAVENCLAD compared to placebo (0.14 vs 0.33, p<0.001). -- 81% of patients were free of relapses after two years of short-course oral treatment with MAVENCLAD, compared to 63% of patients who received placebo (p<0.05). -- Patients treated with MAVENCLAD had a 33% reduction in risk of 3-month confirmed disability progression as measured by Expanded Disability Status Scale (EDSS) compared to placebo (p<0.05). -- Patients taking MAVENCLAD experienced a lower median number of T1-weighted gadolinium-enhanced brain lesions and new or enlarging T2 brain lesions compared to patients with placebo (0 vs 0.33 and 0 vs 0.67) p<0.001).

The most common (> 20%) adverse reactions reported in the pivotal phase III study, CLARITY were upper respiratory tract infection, headache, and lymphopenia. Serious adverse reactions reported in the clinical program included malignancies (0.27 events per 100 patient-years) in MAVENCLAD treatment arms, compared to placebo patients (0.13 events per 100 patient-years), and herpes zoster infections (2.0% vs. 0.2%) and oral herpes (2.6% vs. 1.2%).

Following the administration of two treatment courses, additional courses of MAVENCLAD are not to be administered. Re-treatment with MAVENCLAD during years three and four may further increase the risk of malignancy. The safety and efficacy of reinitiating MAVENCLAD more than two years after completing two treatment courses has not been studied.

Merck is committed to helping support patients prescribed MAVENCLAD. Over the course of 16 years, Merck`s comprehensive patient support program in the U.S., MS LifeLines, has had over four million touchpoints with patients, care partners, health care professionals, and other stakeholders to support our goal of providing one-on-one assistance to U.S. patients prescribed a Merck MS therapy. MS LifeLines is now expanding to help patients prescribed MAVENCLAD and offers personalized patient support, including assistance with navigating insurance questions and additional resources that may be able to assist patients who are uninsured or underinsured.

The U.S. approval of MAVENCLAD follows its approval in over 50 countries, including the European Union in August 2017.

For more information on MAVENCLAD, and prescribing information [https://www.mavenclad.com/en/prescribing-information] including the boxed WARNINGS, visit www.MAVENCLAD.com [http://www.mavenclad.com/].

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1. National MS Society. Secondary progressive MS (SPMS). https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Sec... [https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Sec...]. Accessed March 2019.

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