Vivoryon Therapeutics N.V. Provides Progress Update on
Varoglutamstat Clinical Development for the Treatment of
Alzheimer's Disease
Vivoryon Therapeutics N.V. Provides
Progress Update on Varoglutamstat Clinical Development
for the Treatment
of Alzheimer's Disease
- VIVIAD Phase 2b study in Europe on
track for final data readout Q1/2024
- Data from all 259 randomized
patients presented at AD/PD show no on-target toxicity and no
clinical signs of ARIA, broadening evidence for potential of
varoglutamstat in AD to overcome the safety challenges of other
drug classes
- Coding enrichment strategy
successfully applied for improved baseline assessment of rescuable
deficits in attention and working memory in the study cohort
- VIVA-MIND Phase 2 study in the
U.S. steadily progressing and enrolling at 18 sites; status update
expected in 2H/2023
- DSMB provided unanimous
recommendation to continue VIVIAD without modification to dosing
regimen, supporting rationale for accelerated uptitration to 600 mg
BID dosing
Halle (Saale) / Munich, Germany,
March 28, 2023 –
Vivoryon Therapeutics N.V. (Euronext Amsterdam: VVY; NL00150002Q7)
(Vivoryon), a clinical stage company focused on
the discovery and development of small molecule medicines to
modulate the activity and stability of pathologically altered
proteins, today provided an update on both clinical studies of its
lead candidate, varoglutamstat, a small molecule medicine in
development for the treatment of Alzheimer's disease (AD),
VIVA-MIND (NCT03919162) and VIVIAD (NCT04498650). Furthermore, the
Company presents updated safety data from its European Phase 2b
study, VIVIAD, at the 2023 International Conference on Alzheimer’s
and Parkinson’s Diseases and related neurological disorders (AD/PD)
in Gothenburg, Sweden.
“We are pleased to report that both of our
ongoing studies are progressing steadily, and we continue to
broaden the overall data package for varoglutamstat with
consistently positive incremental results,” commented Dr. Ulrich
Dauer, CEO of Vivoryon. “Varoglutamstat is strongly positioned as a
differentiated oral, outpatient small molecule that has the
potential to significantly impact the AD treatment landscape and
address ongoing unmet need. Designed to modulate all major
hallmarks of AD including Abeta aggregation, neuroinflammation and
tau pathology, and also enabling improvement of synaptic function,
varoglutamstat captures the key features of a novel drug that has
already exhibited a favorable safety profile with no signs of ARIA
side effects. We are incredibly encouraged by what we have been
able to report to date, and we see a unique opportunity for
ultimately realizing the promise of a widely accessible treatment
option in AD with the realistic potential to reach the millions of
patients in need.”
Vivoryon is pursuing a unique and highly
differentiated approach to AD treatment, with a meticulously
designed clinical development strategy. Grounded in the discovery
that the enzyme glutaminyl cyclase (QPCT) catalyzes formation of
the neurotoxic Abeta variant N3pE- Abeta, a key driver of AD
pathology, Vivoryon is pioneering small molecule-based therapies to
block this disease pathway. Varoglutamstat is designed to prevent
N3pE- Abeta formation, rather than aiming to clear existing
plaques, making it an intervention upstream of other approaches
such as monoclonal antibodies (mAbs). Through a second mode of
action, varoglutamstat also modulates neuroinflammation via the
CCL2 pathway, which, in turn, has an impact on tau pathology.
“We are extremely encouraged by the
exceptionally low discontinuation rates in both of our studies,”
added Dr. Michael Schaeffer, CBO of Vivoryon. “Vivoryon is acutely
focused on lessening the burden of AD for both patients and their
families. As we are addressing an elderly patient population, we
know how important it is to design a drug that is convenient. These
patients typically have to live with and manage many different
health conditions at the same time, which heavily impacts their
everyday lives. Many feel overwhelmed by the sheer number of
medicines they have to take every day and it is therefore our goal
to make taking varoglutamstat as easy and convenient as possible.
By investigating options to further optimize the formulation of our
tablets, we feel that we have the unique chance to facilitate
adherence to the correct dosing in our clinical studies and
beyond.”
Clinical
development of
varoglutamstat
Following a meticulously designed clinical
development strategy, varoglutamstat was shown to be well-tolerated
in both a completed first-in-human Phase 1 study in over 200
participants and the subsequent first-in-patient Phase 2a study,
SAPHIR (NCT02389413), which enrolled 120 patients suffering from
early AD. Importantly, after only 12 weeks of treatment, this study
showed evidence of improving not only pathological hallmarks, but
also synaptic function and connectivity, cognition, memory and
attention in AD patients, including statistically significant
changes from baseline in working memory.
Building on these encouraging results, Vivoryon
based the selection of endpoints for both VIVIAD and VIVA-MIND on
the outcome of SAPHIR, as well as on the regulatory draft
guidelines for AD drug development introduced by FDA and EMA in
2018. With these two complementary studies, the Company intends to
assess if potential cognitive improvements in patients in the
European VIVIAD study will translate into an established clinical
endpoint in patients in the U.S. VIVA-MIND study.
VIVIAD: European Phase 2b
study in patients with mild cognitive impairment and mild
AD
VIVIAD is a state-of-the-art Phase 2b study
being conducted in Europe and designed to evaluate the safety,
tolerability and efficacy of varoglutamstat in 250 subjects with
mild cognitive impairment (MCI) and mild AD compared to placebo
over the course of 48 to 96 weeks of treatment. The highest dose
investigated in the study (600 mg twice daily) was selected by an
independent Data Safety Monitoring Board (DSMB) as final dose after
the dose-escalation portion of the study. Enrollment was completed
and the study was adapted to enable longer average treatment
duration of participants (anticipated average treatment duration
~82 weeks) in the third quarter of 2022. The primary endpoint is a
composite of the Neuropsychological Test Battery (NTB) focusing on
changes in working memory and attention with secondary endpoints
including multiple cognitive, safety and biomarker assessments.
Highlights from AD/PD
poster titled, VIVIAD, a
Phase 2b study investigating varoglutamstat in patients with MCI
and mild AD: Update on interim blinded safety results
(Poster P0315/#2631)
- As of the data cut-off date of
January 5, 2023, over 100 of the 259 participants randomized into
the study had been treated for 48 weeks or more
- Varoglutamstat showed no on-target
toxicity and no clinical signs of brain swelling or hemorrhages
(ARIA), a clearly limiting class side effect of Abeta
antibodies
- Overall, varoglutamstat was well
tolerated in the study to date, with all of the adverse events
(AEs) (except for COVID-19 infections) being gastrointestinal,
general, or related to the nervous system or skin. Only 14 serious
AEs (SAEs) have been reported
- A low number of treatment emergent
adverse events (TEAEs) was observed, only 18% of which were
considered to be potentially related to study treatment
- The occurrence of AEs normalized
per 100 visits is stable at 31 and as few as 19 participants (6.5%)
discontinued the study, with only six (2.3%) discontinuing due to
AEs
- Both the total number of SAEs and
the discontinuation rate were considerably lower than the
respective numbers at the 800 mg BID varoglutamstat dose in
Vivoryon’s completed Phase 2a SAPHIR study (15% SAEs, 33%
discontinuation), while retaining a similar level of target
inhibition at the dosing in both studies
- Data from these participants
corroborate the beneficial safety data reported previously for
varoglutamstat, with no on-study deaths, no on-target toxicity and
no clinical signs of ARIA observed
- A new coding enrichment strategy
was applied to ensure that the majority of participants exhibited
rescuable deficits in attention and working memory at baseline,
enabling reliable assessment of potential cognitive improvement
after treatment
- Only five of the 259 participants
exhibited normal performance on cognitive tests of the CogState NTB
at baseline, demonstrating that the strategy of recruiting
individuals with evidence of baseline deficits can be an effective
method of enriching a study cohort
Vivoryon remains on track to report the final data readout from
the VIVIAD study in the first quarter of 2024.
VIVA-MIND: U.S. Phase 2a/b in patients
with early AD
VIVA-MIND is a complementary Phase 2 study being
conducted in the U.S., coordinated by the Alzheimer's Disease
Cooperative Study (ADCS) at the University of California San Diego
(UCSD) School of Medicine and supported by the National Institute
on Aging (NIA), part of the National Institutes of Health (NIH)
with a $15 million grant (NIA award number R01AG061146). The study
seeks to enroll 180 patients into the Phase 2a adaptive
dose-finding portion with the Phase 2b portion, enrolling an
additional 234 patients treated at the selected dose for at least
72 weeks, with a total of 414 patients being treated on stable
doses of varoglutamstat for 18 months. The VIVA-MIND design was
adapted in the third quarter of 2022 to enable all 180 patients to
be treated for at least 72 weeks, allowing for the opportunity to
progress seamlessly to a potential Phase 3 study. The flexible
study design is aimed at increasing the probability of success by
broadening option space for adjustments in clinical development
based on learnings from VIVIAD and other developments in the field.
The primary endpoint for this study is clinical dementia rating
scale - sum of boxes (CDR-SB), an established approvable endpoint
measuring a combination of cognitive abilities and activities of
daily living. Secondary efficacy endpoints include quantitative EEG
theta power, ADAS-Cog 13 and others. Exploratory endpoints include
mini-mental state examination (MMSE), Montreal cognitive assessment
(MoCA), quantitative EEG alpha power, relative QPCT activity in CSF
and others.
Highlighted
study
updates:
- Study is ongoing and continuing to
recruit patients at 18 sites across the U.S. Vivoryon expects the
first cohort to be fully randomized into the study within the
second quarter of this year
- Focus on overcoming the challenges
historically impacting AD drug development with a uniquely designed
study, serving as a complementary to VIVIAD and following a
specific dosing scheme implemented to investigate the feasibility
of an accelerated uptitration regimen
- Objective to reach the 600 mg BID
dose, the final dose selected in the VIVIAD study, without
requiring slow uptitration to reduce the overall burden on patients
and study sites
- The study’s independent Data Safety
Monitoring Board (DSMB) has recently provided the unanimous
recommendation to continue the study without modification
- Study design allows to potentially
transform VIVA-MIND into a Phase 3 study and include further
patients beyond the currently planned 414; the decision on actual
size will be taken after the readout of the VIVIAD study
Vivoryon expects to provide the next update on the VIVA-MIND
study in the second half of 2023.
“As a neurologist confronted with the severe
impact this devastating disease has on peoples’ lives on a daily
basis, I am very pleased to see the progress being made in
Vivoryon’s varoglutamstat studies and the hope that this new
treatment might offer to patients,” commented Dr. Howard Feldman,
Professor of Neurosciences and Director of the ADCS at UC San
Diego, and the VIVA-MIND study director. “While there remains much
to be done in terms of research and development for safe and
effective disease-modifying therapies that are widely available to
patients, I believe that varoglutamstat represents a new approach
to reducing the pathological events in AD. The complementary
studies, VIVIAD and VIVA-MIND, present a strong clinical path
forward for varoglutamstat. It is encouraging to see the VIVA-MIND
trial receive its most recent DSMB recommendation for the trial to
continue forward based on their most recent safety review of March
13, 2023.”
###
About Vivoryon Therapeutics
N.V.Vivoryon is a clinical stage biotechnology company
focused on developing innovative small molecule-based medicines.
Driven by our passion for ground-breaking science and innovation,
we strive to change the lives of patients in need suffering from
severe diseases. We leverage our in-depth expertise in
understanding post-translational modifications to develop medicines
that modulate the activity and stability of proteins which are
altered in disease settings. Beyond our lead program,
varoglutamstat, which is in Phase 2 clinical development to treat
Alzheimer’s disease, we have established a solid pipeline of orally
available small molecule inhibitors for various indications
including cancer, inflammatory diseases and fibrosis.
www.vivoryon.com
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For more information, please contact:
Investor ContactStern IRJulie SeidelTel: +1
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Media ContactTrophic CommunicationsValeria
FisherTel: +49 175 8041816Email: vivoryon@trophic.eu
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