Late-breaking data for Roche’s BTK inhibitor fenebrutinib show brain penetration and significant reduction in lesions in patients with relapsing multiple sclerosis
13 Oktober 2023 - 3:30PM
Late-breaking data for Roche’s BTK inhibitor fenebrutinib show
brain penetration and significant reduction in lesions in patients
with relapsing multiple sclerosis
- New data from Phase II
FENopta study in relapsing multiple sclerosis (RMS) show
fenebrutinib crosses the blood-brain barrier with the potential to
act directly on the chronic inflammation related to multiple
sclerosis (MS)
- More than 90% relative
reduction in new/enlarging T2 lesions and new T1
gadolinium-enhancing (Gd+) lesions with fenebrutinib beginning at 8
weeks
- The safety profile of
fenebrutinib was consistent with previous and ongoing clinical
trials across more than 2,500 people to date
Basel, 13 October 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY)
today announced new data from the Phase II FENopta study showing
that investigational, oral fenebrutinib is brain penetrant and
reduces brain lesions in people with relapsing multiple sclerosis
(RMS) with a consistent safety profile to other fenebrutinib
trials. The late-breaking data were featured in an oral
presentation at the 9th Joint ECTRIMS-ACTRIMS Meeting (European and
Americas Committees for Treatment and Research in Multiple
Sclerosis). “These interesting results raise the possibility that
fenebrutinib slows MS disease progression in part by acting
directly within the brain,” said Levi Garraway, M.D., Ph.D.,
Roche’s Chief Medical Officer and Head of Global Product
Development. “These data, which we are currently confirming in
pivotal trials of both relapsing and progressive MS, suggest that
fenebrutinib may have the potential to counteract acute and chronic
inflammation within the brain to reduce disease activity in people
with MS.” Brain penetrance was measured by the level of
fenebrutinib in the cerebrospinal fluid (CSF) of a subgroup of 11
patients with RMS. After 12 weeks of continuous treatment, the mean
fenebrutinib concentration was 43.1 ng/mL. Similar fenebrutinib
concentrations can produce near-maximal inhibition (IC90) in
preclinical studies. Thus, the level of fenebrutinib in the brain
and central nervous system may conceivably become high enough to
reduce MS disease activity and progression in patients.Fenebrutinib
significantly reduced the total number of new T1
gadolinium-enhancing (T1 Gd+) brain lesions which are markers of
active inflammation, and the total number of new or enlarging
T2-weighted (T2) brain lesions, which represent the amount of
disease burden or chronic lesion load. A rapid onset of lesion
reduction was observed by 4 weeks, with relative reductions of 92%
and 90% in T1 Gd+ lesions and relative reductions of 90% and 95% in
T2 lesions observed at 8 and 12 weeks, respectively.
Furthermore, patients treated with fenebrutinib were four times
more likely to be free from any new T1 Gd+ brain lesions and new or
enlarging T2 brain lesions at weeks 4, 8, and 12 combined, compared
to patients who received placebo (odds ratio 4.005, p=0.0117). The
safety profile of fenebrutinib was consistent with previous and
ongoing fenebrutinib clinical trials across more than 2,500 people
to date. There were no new safety concerns identified in the
FENopta study. Overall rates of adverse events were 38% for
fenebrutinib and 33% for placebo. The most common adverse events
that were higher with fenebrutinib than placebo were abnormal liver
enzyme levels (5.5% fenebrutinib, 0% placebo), headache (4.1%
fenebrutinib, 2.8% placebo), nasopharyngitis (2.7% fenebrutinib, 0%
placebo) and upper abdominal pain (2.7% fenebrutinib, 0% placebo).
Fenebrutinib is the only non-covalent and reversible BTK inhibitor
in Phase III trials for MS and was designed to be highly selective,
which may be important in reducing off-target effects of a molecule
and potentially contribute to long-term safety outcomes. An
open-label extension of FENopta is ongoing, with Phase III studies
FENhance 1 and 2 currently enrolling patients with RMS and
FENtrepid fully enrolled for patients with primary progressive MS
(PPMS). Roche is committed to advancing innovative clinical
research programmes to broaden the scientific understanding of MS,
further reduce disability worsening in RMS and PPMS and improve the
treatment experiences for those living with the disease.
About fenebrutinibFenebrutinib is an
investigational oral, reversible and non-covalent Bruton’s tyrosine
kinase (BTK) inhibitor that blocks the function of BTK. BTK, also
known as tyrosine-protein kinase BTK, is an enzyme that regulates
B-cell development and activation and is also involved in the
activation of innate immune system myeloid lineage cells, such as
macrophages and microglia. Preclinical data have shown fenebrutinib
to be potent and highly selective, and it is the only reversible
inhibitor currently in Phase III trials for MS. Fenebrutinib has
been shown to be 130 times more selective for BTK vs. other
kinases. These design features may be important as the high
selectivity and reversibility can potentially reduce off-target
effects of a molecule.Fenebrutinib is a dual inhibitor of both
B-cell and microglia activation. This dual inhibition may be able
to reduce both MS disease activity and disability progression,
thereby potentially addressing the key unmet medical need in people
living with MS. The Phase III programme includes two identical
trials in RMS (FENhance 1 & 2) with an active teriflunomide
comparator and one trial in PPMS (FENtrepid) in which fenebrutinib
is being evaluated against OCREVUS® (ocrelizumab). To date, more
than 2,500 patients and healthy volunteers have been treated with
fenebrutinib in Phase I, II and III clinical programmes across
multiple diseases, including MS and other autoimmune disorders.
About the FENopta studyThe FENopta study is a
global Phase II, randomised, double-blind, placebo-controlled
12-week study to investigate the efficacy, safety and
pharmacokinetics of fenebrutinib in 109 adults aged 18-55 years
with RMS. The primary endpoint is the total number of new
gadolinium-enhancing T1 lesions as measured by MRI scans of the
brain at 4, 8 and 12 weeks. Secondary endpoints include the number
of new or enlarging T2-weighted lesions as measured by MRI scans of
the brain at 4, 8 and 12 weeks, and the proportion of patients free
from any new gadolinium-enhancing T1 lesions and new or enlarging
T2-weighted lesions as measured by MRI scans of the brain at 4, 8
and 12 weeks. The goal of the FENopta study is to characterise the
effect of fenebrutinib on MRI and soluble biomarkers of disease
activity and progression, and it includes an optional substudy to
measure cerebrospinal fluid biomarkers of neuronal injury. Patients
who complete the double-blind period are eligible for an open-label
extension study. About multiple sclerosisMultiple
sclerosis (MS) is a chronic disease that affects more than 2.8
million people worldwide. MS occurs when the immune system
abnormally attacks the insulation and support around nerve cells
(myelin sheath) in the central nervous system (brain, spinal cord
and optic nerves), causing inflammation and consequent damage. This
damage can cause a wide range of symptoms, including muscle
weakness, fatigue and difficulty seeing, and may eventually lead to
disability. Most people with MS experience their first symptom
between 20 and 40 years of age, making the disease the leading
cause of non-traumatic disability in younger adults.People with all
forms of MS experience disease progression – permanent loss of
nerve cells in the central nervous system – from the beginning of
their disease even if their clinical symptoms aren’t apparent or
don’t appear to be getting worse. Delays in diagnosis and treatment
can negatively impact people with MS, in terms of their physical
and mental health, and contribute to the negative financial impact
on the individual and society. An important goal of treating MS is
to slow, stop and ideally prevent disease activity and progression
as early as possible.Relapsing-remitting MS (RRMS) is the most
common form of the disease and is characterised by episodes of new
or worsening signs or symptoms (relapses) followed by periods of
recovery. Approximately 85% of people with MS are initially
diagnosed with RRMS. The majority of people who are diagnosed with
RRMS will eventually transition to secondary progressive MS (SPMS),
in which they experience steadily worsening disability over time.
Relapsing forms of MS (RMS) include people with RRMS and people
with SPMS who continue to experience relapses. Primary progressive
MS (PPMS) is a debilitating form of the disease marked by steadily
worsening symptoms but typically without distinct relapses or
periods of remission. Approximately 15% of people with MS are
diagnosed with the primary progressive form of the disease. Until
the FDA approval of OCREVUS, there had been no FDA-approved
treatments for PPMS.About Roche in
NeuroscienceNeuroscience is a major focus of research and
development at Roche. Our goal is to pursue ground-breaking science
to develop new treatments that help improve the lives of people
with chronic and potentially devastating diseases. Roche and
Genentech are investigating more than a dozen medicines for
neurological disorders, including MS, spinal muscular atrophy,
neuromyelitis optica spectrum disorder, Alzheimer’s disease,
Huntington’s disease, Parkinson’s disease, acute ischemic stroke,
Duchenne muscular dystrophy and Angelman syndrome. Together with
our partners, we are committed to pushing the boundaries of
scientific understanding to solve some of the most difficult
challenges in neuroscience today. About Roche
Founded in 1896 in Basel, Switzerland, as one of the first
industrial manufacturers of branded medicines, Roche has grown into
the world’s largest biotechnology company and the global leader in
in-vitro diagnostics. The company pursues scientific excellence to
discover and develop medicines and diagnostics for improving and
saving the lives of people around the world. We are a pioneer in
personalised healthcare and want to further transform how
healthcare is delivered to have an even greater impact. To provide
the best care for each person we partner with many stakeholders and
combine our strengths in Diagnostics and Pharma with data insights
from the clinical practice.
In recognising our endeavour to pursue a long-term perspective
in all we do, Roche has been named one of the most sustainable
companies in the pharmaceuticals industry by the Dow Jones
Sustainability Indices for the thirteenth consecutive year. This
distinction also reflects our efforts to improve access to
healthcare together with local partners in every country we
work.
Genentech, in the United States, is a wholly owned member of the
Roche Group. Roche is the majority shareholder in Chugai
Pharmaceutical, Japan.
For more information, please visit www.roche.com.
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