Data Provide Additional Insight into the Mode of Action of Investigational Cladribine Tablets in Patients with Relapsing MS

• Data suggest that cladribine tablets selectively and discontinuously reduces B and T lymphocytes, with lymphocyte counts returning to normal range before the end of Year 2
• The lymphocyte data presented at EAN Congress are consistent with other clinical safety presentations of Cladribine Tablets at the congress

MISSISSAUGA, ON, June 27, 2017 /CNW/ - Merck KGaA, Darmstadt, Germany, a leading science and technology company, operating in Canada as EMD Serono, announced the presentation of safety and efficacy data on investigational cladribine tablets for the treatment of relapsing MS at the 3rd Congress of the European Association of Neurology (EAN), in Amsterdam, the Netherlands. Data from the placebo-controlled CLARITY, CLARITY Extension and ORACLE-MS clinical trials support the benefit: risk profile of cladribine tablets that have prompted an application for marketing authorisation in the EU, and the recent positive opinion from the Committee for Medicinal Products for Human Use (CHMP).

In these studies, cladribine tablets was administered as two annual treatment courses in Years 1 and 2, with a total maximum of 20 days of oral treatment equal to a dose of 3.5 mg/kg body weight, followed by no further active treatment in Years 3 and 4.

"These data presented at EAN Congress 2017 bring the MS treating community closer to understanding the mechanism of action of cladribine tablets," said Professor Per Soelberg Sørensen, presenting author and Head of MS Research Unit, Danish Multiple Sclerosis Centre. "These data support the emerging theories around the ability of some agents to selectively 'reset' the immune system without the secondary autoimmunity that we sometimes see with treatments for relapsing MS. This would represent a significant advance in the field."

Data from three key studies suggest that cladribine tablets selectively and discontinuously reduce both B and T lymphocytes in patients with early and relapsing forms of MS. An early and discontinuous reduction of peripheral blood B cells was seen, with cells numbers reaching a nadir at 13 weeks after treatment, followed by a rapid reconstitution toward baseline. A moderate reduction in T cell counts was also shown, although to a lesser degree than B cells; this reduction was more pronounced in CD4+ than CD8+ lymphocytes.

An exploratory analysis of the CLARITY data suggests that if strict lymphocyte count rules are adhered to before each yearly short course treatment, then the proportion of patients recovering at the end of Year 1 was 89.1% and at the end of Year 2 was 88.3%. Given the clinical effect observed during Years 1 and 2 of dosing in CLARITY, and beyond Years 1 and 2 with CT 3.5 mg/kg in CLARITY EXT, these data demonstrate that the clinical effect observed is achieved without continuous immunosuppression and through selective effects on B and T cell populations.

"Following last week's positive CHMP opinion, this integrated safety data, including 8 years of follow up in some patients, further supports the use of cladribine tablets as a treatment option for patients with MS" said Luciano Rossetti, Global Head of R&D for the biopharma business of Merck KGaA, Darmstadt, Germany.

On 23 June, the Committee for Medicinal Products for Human Use (CHMP) has granted a positive opinion on the use of cladribine tablets for relapsing MS, and this recommendation has been passed on to the European Commission (EC) to make the final decision on the Marketing Authorization Application (MAA) later this year.

Lymphopenia was the most commonly reported adverse event (AE) in patients treated with cladribine tablets. The incidence of infections was 48.3% with cladribine tablets and 42.5% with placebo, with 99.1% and 99.0% rated mild-to-moderate by investigators.

About cladribine tablets
Cladribine tablets is an investigational short-course oral therapy that is thought to selectively and periodically target lymphocytes believed to be integral to the pathological process of MS. Cladribine Tablets is currently under clinical investigation and not yet approved for the treatment for any use in the United States, Canada and Europe. In June 2017, the European Medicines Agency (EMA) accepted for review the Marketing Authorisation Application (MAA) of cladribine tablets for the treatment of relapsing remitting multiple sclerosis.

The clinical development program for cladribine tablets includes:

• The CLARITY (CLAdRIbine Tablets Treating MS OrallY) study: a two-year Phase III placebo-controlled study designed to evaluate the efficacy and safety of cladribine tablets as a monotherapy in patients with RRMS.
• The CLARITY extension study: a four-year Phase III placebo-controlled study following on from the CLARITY study, designed to evaluate the safety and efficacy of cladribine tablets over an extended administration for four years.
• ORACLE MS (ORAl CLadribine in Early MS) study: a two-year Phase III placebo-controlled study designed to evaluate the efficacy and safety of Cladribine Tablets as a monotherapy in patients at risk of developing MS (patients who have experienced a first clinical event suggestive of MS).
• ONWARD (Oral Cladribine Added ON To Interferon beta-1a in Patients with Active Relapsing Disease) study: a Phase II placebo-controlled study designed primarily to evaluate the safety and tolerability of adding Cladribine Tablets treatment to patients with relapsing forms of MS, who have experienced breakthrough disease while on established interferon-beta therapy.
• PREMIERE (Prospective Observational Long-term Safety Registry of Multiple Sclerosis Patients Who Have Participated in Cladribine Clinical Studies) study: interim long-term follow-up data from the prospective registry, PREMIERE, evaluates the safety and efficacy of Cladribine Tablets. The follow-up will consist of over 10,000 patient years of exposure in total, with follow-up in some patients exceeding eight years at completion.

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.

About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany is a leading science and technology company in healthcare, life science and performance materials. Around 50,000 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 2016, Merck KGaA, Darmstadt, Germany generated sales of € 15.0 billion in 66 countries.

Founded in 1668, Merck KGaA, Darmstadt, Germany is the world's oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck KGaA, Darmstadt, Germany 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.

About EMD Serono, Canada
EMD Serono, Canada, is the Canadian biopharmaceutical business of Merck KGaA, Darmstadt, Germany. EMD Serono, Canada has integrated cutting-edge science, innovative products and devices, and industry-leading patient support and access programs. EMD Serono, Canada has deep expertise in neurology, fertility and endocrinology, as well as a robust pipeline of potential therapies in neurology, oncology, immunology and immuno-oncology. Today, EMD Serono, Canada has more than 100 employees across Canada with headquarters in Mississauga, Ontario.

SOURCE EMD Serono

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