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

Darmstadt, Germany (ots/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 EUR 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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ots Originaltext: Merck KGaA
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