DARMSTADT, Germany, February 9, 2017 /PRNewswire/ --
- Post hoc analysis of Phase III CLARITY study data
recently published in Multiple Sclerosis
Journal showed statistically significant reduction in brain
atrophy in patients on a short
course of investigational Cladribine Tablets over two
years compared with patients receiving placebo
- These findings correlated with effects on clinical progression as measured by the EDSS scale, a method of quantifying
disability in multiple sclerosis
Merck, a leading science and technology company, today announced the publication of the results of a post hoc analysis of the
Phase III CLARITY study in Multiple Sclerosis Journal. The analysis showed that Cladribine Tablets reduced the
annualised rate of brain volume loss - also known as brain atrophy - compared with placebo in patients with relapsing remitting
multiple sclerosis (RRMS).
In addition, the analysis found that patients with lower rates of brain atrophy showed the highest probability of remaining
free from disability progression at two years. This supports existing findings that increased brain volume loss over time is
associated with worse clinical outcomes, such as increased disability progression and cognitive changes, in patients with
multiple sclerosis.
"Evidence shows that brain atrophy in general accumulates throughout the course of multiple sclerosis and is associated with
disability progression. This analysis is important because it confirms the link between reduced brain atrophy and reduced
disability progression found in the CLARITY study," said Nicola De Stefano, lead author of the
publication and Associate Professor of Neurology, Department of Medicine, Surgery and Neuroscience, University of Siena.
The CLARITY study was a two-year (96-week), randomised, double-blind, placebo-controlled Phase III study of Cladribine Tablets
in 1,326 people with RRMS. The CLARITY study primary (rate of relapse at 96 weeks) and key secondary endpoints (proportion of
patients who were relapse free and the time to sustained progression of disability) were met. These outcomes and safety results
were published in The New England Journal of Medicine.
The brain atrophy analysis evaluated the effect of Cladribine tablets on brain volume loss (BVL) over 2 years in RMS and the
association of BVL with confirmed disability progression in 1,025 (77.3%) of the patients in CLARITY. The mean percentage brain
volume loss per year was significantly reduced in patients treated with Cladribine Tablets 3.5 mg/kg (-0.56%±0.68, p=0.010,
n=336) and 5.25 mg/kg (-0.57%±0.72, p=0.019, n=351) compared with patients treated with placebo (-0.70%±0.79, n=338). The risk of
disability progression was also significantly lower in patients treated with Cladribine Tablets 3.5 mg/kg (HR 0.63, 95% CI 0.438,
0.894; p=0.010) and 5.25 mg/kg (HR 0.58, 95% CI 0.406, 0.833; p=0.003) than in those treated with placebo. After adjusting for
treatment group, percentage brain volume loss per year showed a significant correlation with the cumulative probability of
disability progression in the overall study population (HR 0.67, 95% CI 0.571, 0.787; p<0.0001).
"These findings reinforce and expand on the consistent and positive effect of Cladribine Tablets in improving clinically
relevant outcomes, such as reducing relapse rate and disability, and further our resolve to make this investigational therapy
available for patients living with RRMS," said Steven Hildemann, MD, PhD, Global Chief Medical
Officer and Head of Global Medical Affairs and Safety, Merck.
CLARITY study design
The CLARITY study was a two-year (96-week), randomised, double-blind, placebo-controlled, international study. It randomised
1,326 patients with relapsing remitting MS according to the revised McDonald criteria. Study participants were randomised to one
of three different treatment groups consisting of two different dose regimens of Cladribine Tablets or matching placebo tablets
(1:1:1 ratio).
The primary endpoint of the CLARITY study was the relapse rate over 96 weeks. Secondary endpoints included MRI endpoints,
proportion of subjects relapse-free and disability progression at 96 weeks.
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 selectively and periodically targets lymphocytes
thought 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 July 2016, 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 and its extension: 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 and its two-year
extension designed to provide data on the long-term safety and efficacy of extended administration of Cladribine Tablets for up
to four years.
- The 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).
- The 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, to evaluate 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. Although many treatments exist there is a
need for an effective therapy without the risks associated with continuous immunosuppression and which reduces the need for
frequent switches.
All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go
to http://www.merckgroup.com/subscribe to
register online, change your selection or discontinue this service.
About Merck
Merck 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 2015, Merck generated sales of € 12.85 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, 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.