ROCKLAND, Mass., May 23, 2020 /PRNewswire/ -- EMD Serono, the
biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada, today announced data on the long-term
efficacy and safety profile of evobrutinib, an investigational,
oral, highly selective Bruton's Tyrosine Kinase (BTK) inhibitor in
adult patients with relapsing multiple sclerosis (RMS). The results
from the Phase II open-label extension (OLE) study will be
presented as a late-breaker at the European Academy of Neurology
(EAN) 2020 Virtual Congress.
"These data demonstrate evobrutinib has a sustained and high
impact on annualized relapse rate over 108 weeks," said
Luciano Rossetti, Head of Global
Research & Development for EMD Serono. "Greatest efficacy was
clearly associated with BTK occupancy, and this further validates
our choice of dose for the Phase III program. We are also
encouraged by evobrutinib's breadth of consistent safety data,
including no increase of serious infections in more than 1,200
patients up to two years."
Annual relapse rate (ARR) results in the double-blind phase of
the study were maintained over the open-label extension, with
patients receiving evobrutinib 75mg BID (twice a day) in the
double-blind phase showing an ARR of 0.11 (95% CI 0.04–0.25) at
week 48, and of 0.12 (0.06–0.22) for the 108-week period.
The data from the Phase II study continues to demonstrate that
BID dosing can achieve higher efficacy than QD dosing on clinical
outcomes, as demonstrated by reduced ARR. Modelling data show that
greater than 95% BTK occupancy at trough is necessary in nearly all
patients to achieve highest efficacy and this can be best achieved
with BID dosing.
Data previously published in the New England Journal of
Medicine reported the findings of the Phase II study where at
24 weeks, evobrutinib significantly reduced the cumulative number
of T1 Gd-enhancing lesions compared to placebo, meeting its primary
endpoint. At week 48, all patients could enter the OLE which
assessed the long-term efficacy and safety of
"The 108-week efficacy and safety data for evobrutinib through
the double-blind and the OLE period are very robust," noted Dr.
Xavier Montalban, Chairman &
Director Neurology-Neuroimmunology Department &
Neurorehabilitation Unit, Multiple Sclerosis Centre of Catalonia
(Cemcat), Vall d'Hebron University Hospital, Barcelona, Spain. "This, combined with the
high selectivity of evobrutinib, suggests that evobrutinib may
offer a promising approach to MS treatment."
Of 267 randomized patients, 213 completed 108 weeks of treatment
(48 weeks in main study and 60 weeks in OLE). Evobrutinib was
generally well-tolerated, with the safety profile maintained during
the OLE including no increase in infections and overall no new
safety signals identified. Consistent with evobrutinib's high
selectivity, patients participating in the trial experienced no
systemic side effects, such as gastrointestinal disturbances. In
the Phase II trial, the most commonly observed adverse events of
any grade associated with evobrutinib included nasopharyngitis and
increases in levels of alanine aminotransferase (ALT), aspartate
aminotransferase (AST) and lipase.
The transient elevated liver aminotransferases were restricted
to the first 24 weeks following evobrutinib treatment initiation
and were not observed in the OLE in patients continuing treatment
Evobrutinib is entering Phase III trials following the results
of the Phase II clinical trial, which met its primary endpoint over
24 weeks of treatment. The two new trials, EVOLUTION RMS 1 and 2
are multi-center, randomised, parallel group, double-blind, double
dummy, active-controlled studies of evobrutinib with teriflunomide,
in participants with RMS. Each trial's primary endpoint is
patients' ARR after 96 weeks of treatment. Secondary endpoints
include the appearance of new or enlarging T2 lesions assessed by
MRI scans and progressing disability as measured by the Expanded
Disability Status Scale (EDSS).
Evobrutinib (M2951) is in clinical
development to investigate its potential as a treatment for
multiple sclerosis (MS). 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. 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. The global Phase III clinical
development programme evaluating evobrutinib in MS includes two
pivotal studies, EVOLUTION RMS 1 and 2. Evobrutinib is currently
under clinical investigation and not approved for any use anywhere
in the world.
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.
EMD Serono, Inc. and Multiple Sclerosis
For more than
20 years, EMD Serono has been relentlessly focused on understanding
the journey people living with MS face in order to create a
meaningful, positive experience for them and the broader MS
community. However, there is still much that is unknown about this
complex and unpredictable disease. EMD Serono is digging deeper to
advance the science.
About EMD Serono, Inc.
EMD Serono - the
biopharmaceutical business of Merck KGaA, Darmstadt, Germany,
in the U.S. and Canada - is engaged in the discovery,
research and development of medicines for patients with difficult
to treat diseases. The business is committed to transforming lives
by developing and delivering meaningful solutions that help address
the therapeutic and support needs of individual patients. Building
on a proven legacy and deep expertise in neurology, fertility and
endocrinology, EMD Serono is developing potential new oncology and
immuno-oncology medicines while continuing to explore potential
therapeutic options for diseases such as psoriasis, lupus and MS.
Today, the business has approximately 1,500 employees around the
country with commercial, clinical and research operations based in
the company's home state
of Massachusetts. www.emdserono.com.
Alice McGrail 1-781-738-8791
SOURCE EMD Serono