Positive Phase II Data Further Highlights Clinical Proof of Concept for Evobrutinib, First Oral Bruton´s Tyrosine Kinase (BTK) Inhibitor to Report Positive Phase II Clinical Results in MS

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- 48-week results provide additional evidence of relapse reduction
for investigational evobrutinib
- Evobrutinib demonstrated rapid lesion reductions on MRI at week 12
that were maintained through week 48, with no new safety signals
identified over 52 weeks
- Data presented at the American Academy of Neurology 2019 Annual
Meeting and simultaneously published in the NEJM

Darmstadt, Germany (ots/PRNewswire) - Merck, a leading science and
technology company, today announced new 48-week results of the
double-blind, randomised, placebo-controlled, Phase II study of
evobrutinib in patients with relapsing multiple sclerosis (RMS). The
results have been presented at the American Academy of Neurology
(AAN) 2019 Annual Meeting in Philadelphia, United States with
simultaneous publication in the New England Journal of Medicine
(NEJM) (http://www.nejm.org/doi/full/10.1056/NEJMoa1901981).
Evobrutinib is the first oral, highly selective Bruton's tyrosine
kinase (BTK) inhibitor to show clinical proof of concept in RMS.

Previously reported data showed that the study had met its primary
endpoint over 24-weeks of treatment, where the total cumulative
number of T1 gadolinium-enhancing lesions was reduced with
evobrutinib compared with placebo. With evobrutinib 75 mg QD (once a
day) and 75 mg BID (twice a day), rapid reductions in number of T1
Gd+ lesions were observed by week 12 of treatment. New data showed
that the effect on T1 gadolinium-enhancing lesions reduction seen at
week 12 was maintained through 48 weeks with evobrutinib 75 mg QD and
75 mg BID.

"These positive Phase II evobrutinib data are a great example of
the strength of our pipeline and commitment to developing new,
innovative treatments in multiple sclerosis," said Luciano Rossetti,
Head of Global Research & Development for the Biopharma business of
Merck. "As a leader in autoimmune diseases and MS we are proud of
this in-house discovery at Merck. We look forward to continuing to
investigate the potential of evobrutinib as we continue to address
unmet patient needs in MS care."

With evobrutinib 75 mg BID, annualized relapse rate (ARR)
(confidence interval) was 0.11 (0.04-0.25) with 79 percent of
patients remaining relapse free over 48 weeks of treatment. For
reference, at 24 weeks, ARR for evobrutinib 75 mg BID was 0.08
(0.01-0.30) and 0.37 (0.17-0.70) for placebo.

No treatment associated infections, infestations, or lymphopenia
were observed and no new safety signals were identified over 52
weeks. The most common treatment-related TEAEs (>10%) included
nasopharyngitis and increased ALT. The percentage of shifts from
baseline to Grade 2 or greater in ALT were 5.7%, 3.8%, and 13% in the
evobrutinib 25mg QD, 75mg QD and 75mg BID groups, respectively. The
corresponding shifts in ALT in the placebo group over 24 weeks was
7.5%. All events had an onset within 24 weeks of treatment initiation
and were reversible on treatment discontinuation with no clinical
consequences within the 52-week study period. During the course of
the study, 85 percent of patients (227 out of 267) completed 52 weeks
of treatment.

"Building on our initial analysis at 24 weeks, these new data
further demonstrate the potential role of evobrutinib in relapsing
multiple sclerosis, subject to further clinical investigation" said
Dr. Xavier Montalban, Professor of Medicine and Department Division
Director, Neurology, at the University of Toronto and Director of the
MS Centre at St. Michael's Hospital, Canada, and Chairman & Director
Neurology-Neuroimmunology Department & Neurorehabilitation Unit,
Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d'Hebron
University Hospital, Barcelona, Spain. "Evobrutinib is the first
Bruton's tyrosine kinase inhibitor to demonstrate clinical proof of
concept in multiple sclerosis. We are pleased that these 48-week data
further support our continued clinical development of evobrutinib and
investigation into its efficacy for patients with MS."

These 48-week results are a new analysis following the initial
24-week presentation of the data at the 34th Congress of the European
Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)
in Berlin, Germany, on October 12, 2018.

Merck presented a total of 20 abstracts (18 posters and two
platform presentations) during AAN 2019. For further information on
the evobrutinib 48-week abstract please see here:

- Efficacy and Safety of the Bruton's Tyrosine Kinase Inhibitor
Evobrutinib in Patients with Relapsing Multiple Sclerosis over 48
Weeks: a Randomized, Placebo-Controlled, Phase 2 Study (http://inde
xsmart.mirasmart.com/AAN2019/SearchResults.php?q=evobrutinib+) -
presented at 13:33 ET on Friday 10 May during the S56: MS Trials
and Treatment session.

The presentation of these data read-outs showcases the breadth of
Merck's multiple sclerosis (MS) portfolio and further underscores its
commitment to the advancement of MS treatment.

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About Evobrutinib

Evobrutinib (M2951) is in clinical development to investigate its
potential as a treatment for multiple sclerosis (MS), rheumatoid
arthritis (RA) and systemic lupus erythematosus (SLE). It is an oral,
highly selective inhibitor of Bruton's tyrosine kinase (BTK) which is
important in the development and functioning of various immune cells
including B lymphocytes and macrophages. Selectivity has been
assessed in vitro. Evobrutinib is designed to inhibit primary B cell
responses such as proliferation and antibody and cytokine release,
without directly affecting T cells. BTK inhibition is thought to
suppress autoantibody-producing cells, which preclinical research
suggests may be therapeutically useful in certain autoimmune
diseases. Evobrutinib is currently under clinical investigation and
not approved for any use anywhere in the world.

About the Evobrutinib Multiple Sclerosis Phase II Study

This double-blind, placebo-controlled, 48-week, Phase II study
evaluates the safety and efficacy of evobrutinib in patients aged
18-65 years with relapsing multiple sclerosis (RMS). Patients were
randomised to evobrutinib 25mg QD, 75mg QD, 75mg BID, PBO or
open-label dimethyl fumarate (240mg BID; reference arm). The primary
endpoint was the sum of T1 gadolinium-enhancing lesions at weeks 12,
16, 20, and 24. Key secondary endpoints included annualised relapse
rate (ARR) at week 48 and safety. For more information about the
study, visit ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/
study/NCT02975349?term=evobrutinib&rank=6&show_locs=Y#locn).

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 Immunology

Merck has a long-standing legacy in immunology, with significant
R&D and commercial experience in multiple sclerosis. Merck`s robust
immunology pipeline focuses on discovering new therapies that have
the potential to modulate key pathogenic mechanisms in chronic
diseases such as MS, systemic lupus erythematosus (SLE) and forms of
arthritis, including rheumatoid arthritis (RA) and osteoarthritis
(OA).

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.

Your Contact
Tone Brauti Fritzen
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Phone: +49-151-1454-2694

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