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Darmstadt, Germany (ots/PRNewswire) -

- MAVENCLAD® is now approved in 52 countries worldwide
- Approval brings forward new treatment option with a novel mechanism
for highly active relapsing multiple sclerosis in Switzerland
- Approval based on extensive clinical development program capturing
more than 10,000 patient years of safety data and up to 10 years of
follow-up in some patients
- MAVENCLAD® provides the possibility of up to four years of disease
control with a maximum of 20 days of oral treatment administered
over two years

Merck, a leading science and technology company, today announced
that MAVENCLAD® (cladribine tablets) has been approved for the
treatment of highly active relapsing remitting multiple sclerosis*
(RRMS)[1] in Switzerland. MAVENCLAD® is the first treatment for RRMS
that provides the possibility of up to four years of disease control
with a maximum of 20 days of oral treatment administered over two
years.

"The Swissmedic approval of MAVENCLAD is great news for patients
in Switzerland with highly active relapsing remitting MS," said
Luciano Rossetti, Head of Global Research & Development for the
Biopharma business of Merck. "These patients have had limited
treatment options and MAVENCLAD, now approved in 52 countries
worldwide, represents an important new therapy with a novel mechanism
as the first short-course oral treatment for relapsing remitting MS
in Switzerland."

MAVENCLAD® has demonstrated durable clinical efficacy for up to
four years across key measures of disease activity, including
disability progression, annualized relapse rate and magnetic
resonance imaging (MRI) activity. The approval of MAVENCLAD® is based
on more than 10,000 patient years of data with over 2,700 patients
included in the clinical trial program, and up to 10 years of
observation in some patients. The clinical development program
included data from three placebo-controlled Phase III trials, CLARITY
(pivotal efficacy study)[2],[3] CLARITY EXTENSION[4] and ORACLE
MS,[5] the Phase II ONWARD study;[6] and long-term follow-up data
from the 8-year prospective registry, PREMIERE.[7] The efficacy and
safety results of these studies allowed for a full characterization
of the benefit-to-risk profile of MAVENCLAD®.

"To receive a reliably effective therapy remains the most
important consideration for patients," said Professor Ludwig Kappos,
Chair, Neurology, University Hospital Basel, Switzerland. "The medium
and long-term treatment risks ought to be as low as possible. Last
but not least the treatment should be very compatible with a normal
daily life. The approval of MAVENCLAD for highly active relapsing
remitting multiple sclerosis by Swissmedic in Switzerland is good
news because it extends the range of options for this group of MS
patients with an oral treatment with proven, long-lasting effect."

In patients with high disease activity, post hoc analyses of the
two-year Phase III CLARITY trial2,[8] demonstrated that MAVENCLAD®
reduced the annualized relapse rate by 67% and the risk of 6-month
confirmed Expanded Disability Status Scale (EDSS) progression by 82%
versus placebo. As demonstrated in the Phase III CLARITY EXTENSION
study, no further MAVENCLAD® treatment was required in Years 3 and
4.[9] MAVENCLAD® has a well-characterized safety profile, with up to
ten years of observation in some patients and no reported cases of
progressive multifocal leukoencephalopathy (PML) in MS. The most
clinically relevant adverse reactions were lymphopenia and herpes
zoster. Lymphocyte counts must be assessed before, and during,
treatment with MAVENCLAD®. MAVENCLAD® is contraindicated in certain
groups including immunocompromised patients and pregnant women.

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About MAVENCLAD®

MAVENCLAD® is a short-course oral therapy that selectively and
periodically targets lymphocytes thought to be integral to the
pathological process of relapsing MS (RMS). In August 2017, the
European Commission (EC) granted marketing authorization for
MAVENCLAD® for the treatment of relapsing forms of multiple sclerosis
(RMS) in the 28 countries of the European Union (EU) in addition to
Norway, Liechtenstein and Iceland. MAVENCLAD® has since then been
approved in more than 50 countries, including Canada and Australia.
MAVENCLAD® is currently under clinical investigation and not yet
approved for the treatment for any use in the United States.

Visit www.MAVENCLAD.com for more information.

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 Phase III placebo-controlled study
following on from the CLARITY study, which evaluated the safety and
exploratory efficacy of cladribine tablets over two additional
years beyond the two-year CLARITY study, according to the treatment
assignment scheme for years 3 and 4.
- 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) study: a long-term observational follow-up
safety registry of MS patients who participated in cladribine
tablets clinical studies.

In the two-year CLARITY study, the most commonly reported adverse
event (AE) in patients treated with cladribine tablets was
lymphopenia (26.7% with cladribine tablets and 1.8% for placebo). The
incidence of infections was 48.3% with cladribine tablets and 42.5%
with placebo, with 99.1% and 99.0% respectively rated
mild-to-moderate by investigators. Adverse Events reported in other
clinical studies were similar.2

Swiss Indication and Important Safety Information

Mavenclad® (10 mg cladribine)

I: Adult patients with highly active relapsing-remitting multiple
sclerosis (MS), as defined by clinical or imaging findings. PO: Dose
of 3.5 mg/kg body weight over 2 years, administered as 1 treatment
phase of 1.75 mg/kg per year. CI: Hypersensitivity to cladribine or
any of the excipients. Infection with the human immunodeficiency
virus (HIV). Severe active infections, active chronic infection (e.g.
tuberculosis or hepatitis). Initiation of treatment in
immunocompromised patients. Existing active malignant disease.
History of progressive multifocal leukoencephalopathy. Moderate or
severe impairment of renal function. Children and adolescents under
18 years. Pregnancy and breast-feeding. W: General: Not recommended
in patients with inactive disease or stabilised on established
therapy. No more than 2 annual treatment phases within 4 years.
Haematological monitoring: The lymphocyte count must be determined
before the start of treatment with Mavenclad in year 1 and year 2, as
well as 2 and 6 months after initiation of treatment in each year of
treatment. Infections: Cladribine can weaken the body's immune system
and potentially increase the likelihood of infection. Patients with
lymphocyte counts below 500 cells/mm3 must be actively monitored for
signs and symptoms of infection, especially herpes zoster. Malignant
disease: Cladribine interferes with DNA synthesis and has an
immunosuppressive effect. Contraception: Reliable contraceptive
methods must be used during treatment with cladribine and for at
least 6 months after the last dose. Blood transfusions: In patients
requiring blood transfusions, irradiation of the cellular blood
components is recommended prior to transfusion. Switching to
cladribine and from cladribine to other medicinal products: Before
starting treatment with Mavenclad, the mechanism of action and
duration of action of the other medicinal product should be taken
into account. Renal disease: Mavenclad must not be used in cases of
moderate or severe impairment of renal function. Hepatic disease:
Mavenclad is not recommended in cases of moderate or severe
impairment of liver function. Fructose intolerance: Patients with
fructose intolerance should not take Mavenclad. IA: Mavenclad
contains hydroxypropylbetadex, which may be able to form complexes
with other medicinal products and hence lead to increased
bioavailability of these medicinal products. Haematotoxic or
immunosuppressive medicines (methotrexate, cyclophosphamide,
ciclosporin, azathioprine, corticosteroids). Other disease-modifying
drugs. Haematotoxic medicines (carbamazepine). Live vaccines and live
attenuated vaccines. Potent inhibitors of ENT1, CNT3 and BCRP
transporters (such as dilazep, nifedipine, nimodipine, cilostazol,
sulindac, reserpine). Potent inducers of BCRP and P-gp transporters
(e.g. corticosteroids and rifampicin, St. John's wort). Hormonal
contraceptives. Most common UE: lymphopenia, oral herpes, dermatomal
herpes zoster, reduction in neutrophil count, rash, alopecia. P:
Mavenclad 10 mg: 1, 4 or 6 tablets. [A] For detailed information, see
www.swissmedicinfo.ch. FEB19

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.

Merck in Multiple Sclerosis

Merck has a long-standing legacy in neurology and immunology, with
significant R&D and commercial experience in multiple sclerosis (MS).
Merck's current portfolio includes two products for the treatment of
relapsing MS, with a robust pipeline focusing on discovering new
therapies that have the potential to modulate key pathogenic
mechanisms in MS. Merck aims to improve the lives of those living
with MS, by addressing areas of unmet medical needs.

About Merck

Merck, a leading science and technology company, operates across
healthcare, life science and performance materials. Around 52,000
employees work to make a positive difference to millions of people's
lives every day by creating more joyful and sustainable ways to live.
From advancing gene editing technologies and discovering unique ways
to treat the most challenging diseases to enabling the intelligence
of devices - the company is everywhere. In 2018, Merck generated
sales of EUR 14.8 billion in 66 countries.

Scientific exploration and responsible entrepreneurship have been
key to Merck's technological and scientific advances. This is how
Merck has thrived since its founding in 1668. The founding family
remains the majority owner of the publicly listed company. Merck
holds the global rights to the Merck name and brand. The only
exceptions are the United States and Canada, where the business
sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma
in life science, and EMD Performance Materials.

* Defined as: patients with one relapse during the previous year
and >= 1 T1 Gd+ lesion or >= 9 T2 lesions while on therapy with other
disease modifying drugs (DMD); OR patients with >= 2 or more relapses
in the previous year, whether on DMD treatment or not.

References:

[1] MAVENCLAD® Summary of Product Characteristics February 2019

[2] Giovannoni G, Comi G, Cook S et al. A Placebo-Controlled Trial
of Oral Cladribine for Relapsing Multiple Sclerosis. 2010 New England
Journal of Medicine 362:416-426

[3] Giovannoni G et al. Sustained disease-activity-free status in
patients with relapsing-remitting multiple sclerosis treated with
cladribine tablets in the CLARITY study: a post-hoc and subgroup
analysis. Lancet Neurol 2011; 10:329-337

[4] EU Clinical Trials Register. A Phase IIIb, Double-Blind,
Placebo-Controlled, Multicenter, Parallel Group, Extension Trial to
Evaluate the Safety and Tolerability of Oral Cladribine in Subjects
with Relapsing-Remitting Multiple Sclerosis Who Have Completed Trial
25643 (CLARITY). Available at https://www.clinicaltrialsregister.eu/c
tr-search/trial/2007-000381-20/results. Last accessed March 2019

[5] Leist T, Comi G, Cree B et al. Effect of oral cladribine on
time to conversion to clinically definite multiple sclerosis in
patients with a first demyelinating event (ORACLE MS): a phase 3
randomised trial. Lancet Neurol 2014; 13: 257-67

[6] EU Clinical Trials Register. A phase II, multicenter,
randomized, double-blind, placebo-controlled, safety, tolerability
and efficacy study of add-on Cladribine tablet therapy with Rebif New
Formulation in Multiple Sclerosis Subjects with Active Disease.
Available at https://www.clinicaltrialsregister.eu/ctr-search/trial/2
006-003366-33/results. Last accessed March 2019

[7] Schreiner T, Miravalle A. Current and Emerging Therapies for
the Treatment of Multiple Sclerosis: Focus on Cladribine. Journal of
Central Nervous System Disease. 2012; 4: 1-14

[8] Giovannoni G, 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. 2018
Multiple Sclerosis Journal 1-9 [Epub ahead of print]

[9] Giovannoni G, Sorensen P, Cook S et al. Safety and efficacy of
cladribine tablets in patients with relapsing-remitting multiple
sclerosis: Results from the randomized extension trial of the CLARITY
study. 2018 Multiple Sclerosis Journal 24(12) 1594-1604

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