Mavenclad (Cladribine Tablets) Data in Multiple Sclerosis Journal Show an Even Greater Treatment Effect in Patients With Highly Active Multiple Sclerosis

DARMSTADT, Germany, April 25, 2018 /PRNewswire/ —

— Post-hoc analysis from the 2-year CLARITY study demonstrated that Mavenclad reduced the risk of 6-month EDSS progression by 47% vs placebo

 — Patients with highly active multiple sclerosis had an even greater treatment effect, reducing the risk by 82% vs placebo  

Merck, a leading science and technology company, today announced the Multiple Sclerosis Journal publication of data outlining the effects of MAVENCLAD^® (cladribine tablets) treatment on two subgroups of patients with highly active relapsing multiple sclerosis (MS)^[1]. These results reaffirm the clinical and radiological efficacy previously demonstrated with MAVENCLAD treatment in patients with relapsing MS.

«This analysis provides valuable insights on the effect of Mavenclad on patients with ongoing disease activity despite treatment with platform therapy, as well as naïve patients with more relapses at baseline, who tend to do worse over time,» said Prof. Gavin Giovannoni, a lead investigator in the CLARITY studies and Chair of Neurology, Barts and The London School of Medicine and Dentistry. «The efficacy data presented in this publication show an even greater risk reduction on expanded disability status scale (EDSS) progression with Mavenclad in patients with highly active MS.»

In this post-hoc analysis, two clinically relevant definitions of high disease activity were selected to effectively identify patients more likely to experience disease progression. Patients from the CLARITY study with high disease activity were categorized by fulfilling one of two overlapping criteria, which reflect those included in the EU SmPC for MAVENCLAD:

• High Relapse Activity (HRA): Patients with ≥2 relapses during the year prior to study entry, whether on disease-modifying drug (DMD) treatment or not
• High Relapse Activity plus Disease Activity on Treatment (HRA + DAT): patients with ≥1 relapse and ≥1 T1 Gadolinium-enhancing (Gd) + or ≥9 T2 lesions during the year prior to study entry while on therapy with other DMDs, plus patients with ≥2 relapses during the year prior to study entry, whether on DMD treatment or not

«Merck is committed to deepening our understanding of the benefit-risk profile of this innovative MS treatment in patient populations with a high need for an effective disease-modifying therapy,» said Luciano Rossetti, Head of Global R&D for the biopharma business of Merck.

HRA and HRA + DAT patients showed clinical and MRI responses to MAVENCLAD that were generally better than, or at least comparable with, the outcomes previously seen in the overall CLARITY study population. In both high disease subgroups, MAVENCLAD was shown to reduce the risk of 6-month EDSS progression by 82% vs placebo, compared to a 47% reduction in the overall CLARITY study population. The newly published analysis also evaluated disease-free status, showing that in the HRA + DAT subgroup, treatment with MAVENCLAD was significantly more likely to result in NEDA* (odds ratio^† 7.82 (95% CI 4.03-15.19; p<0.0001) when compared with the non-HRA + DAT subgroup 4.46 (95% CI 3.13-6.26)). The HRA subgroup was also more likely to achieve NEDA, but a statistically significant difference was not observed when compared to the non-HRA group.

The relative risk of cumulative new T1 Gd+ lesions for patients in both high-disease subgroups treated with MAVENCLAD was low, with strong effects observed in each treatment subgroup. Overall, the subgroup-specific safety analysis for patients with HRA and HRA+DAT did not reveal evidence for new safety findings compared with those previously described for the overall CLARITY population.

About MAVENCLAD^®

In August 2017, the European Commission (EC) granted marketing authorization for MAVENCLAD^® for the treatment of relapsing forms of MS (RMS) in the 28 countries of the European Union (EU) in addition to Norway, Liechtenstein and Iceland. MAVENCLAD^® is now available in Germany, Canada, Australia, Argentina, United Arab Emirates, Israel, Luxembourg, Denmark, Norway, Scotland and the UK. MAVENCLAD^® is not yet approved for any use in the United States.

MAVENCLAD^® (cladribine tablets) is a short-course oral therapy that selectively and periodically targets lymphocytes thought to be integral to the pathological process of multiple sclerosis (MS). The clinical development program of Cladribine in MS comprises more than 10,000 patient years of data with over 2,700 patients included in the clinical trial program, and more than 10 years of observation in some patients.

EU Indication

MAVENCLAD^® (cladribine tablets) is indicated for the treatment of adult patients with highly active relapsing multiple sclerosis (RMS) as defined by clinical or imaging features.

Important EU Safety Information

Contraindications:

MAVENCLAD^® is contraindicated in patients with hypersensitivity to the active substance, human immunodeficiency virus (HIV), active chronic infection (tuberculosis or hepatitis), active malignancy, moderate to severe renal impairment (creatinine clearance <60 mL/min), and those who are pregnant and breast-feeding. MAVENCLAD^® is also contraindicated in immunocompromised patients, including patients currently receiving immunosuppressive or myelosuppressive therapy.

Special warnings and precautions for use:

The most clinically relevant adverse reactions were lymphopenia and herpes zoster.

Haematology

Decreases in neutrophil count, red blood cell count, haematocrit, haemoglobin or platelet count compared to baseline values have been observed in clinical studies, although these parameters usually remain within normal limits.

Additive haematological adverse reactions may be expected if cladribine is administered prior to or concomitantly with other substances that affect the haematological profile

Lymphocyte counts must be determined

• before initiating MAVENCLAD^® in year 1,
• before initiating MAVENCLAD^® in year 2,
• 2 and 6 months after start of treatment in each treatment year. If the lymphocyte count is below 500 cells/mm³, it should be actively monitored until values increase again.

Infections

Cladribine can reduce the body’s immune defence and may increase the likelihood of infections. HIV infection, active tuberculosis and active hepatitis must be excluded before initiation of cladribine.

The incidence of herpes zoster was increased in patients on cladribine. If lymphocyte counts drop below 200 cells/mm³, anti-herpes prophylaxis according to local standard practice should be considered during the time of grade 4 lymphopenia. Interruption or delay of MAVENCLAD^® may be considered until proper resolution of the infection.

Cases of progressive multifocal leukoencephalopathy (PML) have been reported for parenteral cladribine in patients treated for hairy cell leukaemia with a different treatment regimen.

In the clinical study data base of cladribine in MS (1,976 patients, 8,650 patient years) no case of PML has been reported. However, a baseline magnetic resonance imaging (MRI) should be performed before initiating MAVENCLAD^® (usually within 3 months).

About Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory condition of the central nervous system and is the most common, non-traumatic, disabling neurological disease in young adults. It is estimated that approximately 2.3 million people have MS worldwide. While symptoms can vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs and problems with strength and coordination. The relapsing forms of MS are the most common.

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About Merck

Merck is a leading science and technology company in healthcare, life science and performance materials. More than 52,000 employees work to further develop technologies that improve and enhance life — from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2017, Merck generated sales of € 15.3 billion in 66 countries.

Founded in 1668, Merck is the world’s oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.

1. Giovannoni G, Soelberg Sorensen P, Cook S et al. Efficacy of cladribine tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post-hoc analysis of the CLARITY study. Multiple Sclerosis Journal. May 2018,http://journals.sagepub.com/doi/full/10.1177/1352458518771875

[*] No evidence of disease activity (NEDA) was defined as patients having no relapses, no 3-month confirmed EDSS worsening, no T1 Gd+ lesions and no active T2 lesions

[†] Odds ratio (OR) is a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure

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Erin-Marie Beals, +49-151-1454-2694