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Prilenia
Announces Clinical Data in Support of its Plans to Initiate Global Phase 3 Study in
ALS
2024-01-19
·
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NAARDEN, Netherlands & WALTHAM, Mass.--(BUSINESS WIRE)--
Prilenia Therapeutics B.V.
, a clinical stage biotechnology company focused on the urgent mission to develop novel therapeutics to slow the progression of
neurodegenerative diseases
and
neurodevelopmental disorders
, will present clinical data supporting a future Phase 3 study in
amyotrophic lateral sclerosis (ALS)
during the 14th Annual California
ALS
Research Summit in Los Angeles. The Company has completed discussions with global regulatory agencies regarding the next stage of development of
pridopidine
for
ALS
and is planning for a single pivotal Phase 3 study to start in H2 2024.
Pridopidine
is an investigational oral, small molecule, highly selective and potent Sigma-1 Receptor (S1R) agonist being studied as a potential treatment for
ALS
and
Huntington’s disease (HD)
. The
S1R
is highly expressed in the brainstem and spinal cord, areas implicated in
ALS
and important for bulbar function and speech. “Based on the clinical data generated to date,
pridopidine
has the potential to become a meaningful treatment for
ALS
, slowing key measures of disease progression, including function, respiration, quality of life and impact on speech, which is very meaningful for patients and caregivers, as well as prolonging overall survival,” said Dr. Michael R. Hayden, CEO and Founder of
Prilenia
. “We believe it is important for
Prilenia
to advance our clinical program in
ALS
, and we are actively planning a single, global, pivotal Phase 3 clinical trial. Our sincere appreciation to the many
ALS
patients, caregivers and healthcare providers who have contributed so much to our clinical studies as well as to those who will participate in future trials. We also are grateful to Dr. Merit Cudkowicz and the entire team at the Sean M. Healey & AMG Center for
ALS
for their innovative and passionate approach to evaluating
pridopidine
as we continue our close working relationship.” “In the Phase 2 clinical trial,
pridopidine
showed encouraging results for the potential treatment of
ALS
across multiple secondary and exploratory measures with an excellent safety profile, and we are pleased to work closely with
Prilenia
on the advancement of this program into Phase 3,” said Merit Cudkowicz, M.D., MSc, principal investigator and sponsor of the HEALEY
ALS
Platform Trial, Director of the Sean M. Healey & AMG Center for
ALS
, Chair of the Department of Neurology at
Massachusetts General Hospital
and the Julieanne Dorn Professor of Neurology at Harvard Medical School. While
pridopidine
did not meet the primary outcome measure, data from the Phase 2 HEALEY
ALS
Platform Trial evaluating the safety and efficacy of
pridopidine
as a potential treatment for
ALS
show in the pre-specified subgroup of participants with definite
ALS
who were also early in the course of the disease (less than 18 months from symptom onset) that
pridopidine
was associated with slower disease progression relative to placebo in ALSFRS-R (Δ2.4, p=0.19), respiratory domain (Δ1.04, p=0.18), and dyspnea (Δ1.35, p=0.014). Less worsening was observed on the ALSAQ-40 quality of life scale (Δ-10.83, p=0.018) and its eating and drinking (Δ-19.18, p=0.015) and communication (Δ-13.04, p=0.12) domains.
Pridopidine
was also observed to have beneficial effects compared to placebo in speech in the full analysis set (speaking rate, p=0.027, articulation rate p=0.0129, phonation time p=0.076, and articulation precision p=0.1138). Speech is a highly clinically relevant endpoint in
ALS
, and measures of speech are associated with overall
ALS
and
bulbar disease
severity. As
ALS
progresses, it is common for patients to have difficulty speaking due to weakening muscles (dysarthria). This poses significant communications challenges with family, friends and healthcare providers. Additional analyses from the same Phase 2 study of participants with definite or probable
ALS
who were also early and fast progressors were conducted. In this subgroup, there was a significant and meaningful (41 percent) slowing of disease progression compared to placebo at 24 weeks in ALSFRS-R (Δ5.2, p=0.04). This slowing of disease progression was already observed at 8 weeks (44.5 percent, p=0.02) and 16 weeks (52 percent, p=0.014). This group also showed greatest improvements vs placebo in ALSFRS-R respiratory domain (Δ1.81, p=0.08),
dyspnea
(Δ1.41, p=0.019), speaking rate (Δ1.08, p=0.00004) and articulation rate (Δ1.03, p=0.00002). Furthermore, survival benefits from post-hoc analyses of the placebo-controlled and open-label extension portions of the study show that
pridopidine
provided an increase in survival time for the specific subgroup consisting of participants with definite or probable
ALS
who were also early in the course of the disease. A Kaplan-Meier survival analysis showed a prolongation of median survival time from ~300 to 600 days in these participants compared to the delayed-start placebo participants (log rank test: p=0.069). The Cox Proportional Hazard Ratio (HR), adjusted for baseline characteristics, was 0.429 (p=0.052), representing a 57 percent improvement in survival benefit. Altogether, these results are encouraging and further inform the ongoing planning of a Phase 3 study. In collaboration with
Massachusetts General Hospital
and the Healey Center and through the ACT for
ALS
(Accelerating Access to Critical Therapies for
ALS
Act), the
National Institutes of Health (NIH)
has provided a grant to support expanded access to
pridopidine
for 200 persons with
ALS
in the U.S. who are not eligible for active clinical trials. Preliminary topline results in the full analysis set of this Phase 2 study were previously announced.
Pridopidine
was well-tolerated with no serious treatment-related adverse events, with a safety and tolerability pro to placebo and consistent with previous clinical studies. About
Pridopidine
and the Sigma-1 Receptor (S1R)
Pridopidine
(45 mg twice daily) is an oral, highly selective, and potent investigational
S1R
agonist that has exhibited a safety and tolerability pro to placebo in clinical studies to date. The
S1R
protein is highly expressed in the brain and spinal cord, where it regulates several key processes that are commonly impaired in various
neurodegenerative diseases
. Activation of the
S1R
by
pridopidine
stimulates multiple cellular protective pathways, including autophagy, axonal transport, mitochondrial energy production and calcium homeostasis, which are essential to neuronal function and survival, and may lead to neuroprotective effects. Mutations in the
S1R
gene cause
ALS
with the time of onset related to the expression of the
S1R
gene. For example, patients with no
S1R
protein have juvenile-onset
ALS
, while patients with diminished
S1R
expression have adult-onset
ALS
. The
S1R
positively regulates key cellular pathways that are commonly impaired in
ALS
and other
neurodegenerative diseases
. In
ALS
cell culture and mouse models,
pridopidine
has been shown to be neuroprotective, specifically mediated via the activation of
S1R
.
Prilenia
holds Orphan Drug designation for
pridopidine
in
ALS
and
Huntington’s Disease (HD)
in the U.S. and EU. In addition,
pridopidine
has received Fast Track designation by the
U.S. Food and Drug Administration (FDA)
for the treatment of HD.
Pridopidine
is not yet approved in the U.S. or EU. About the HEALEY
ALS
Platform Study –
Pridopidine
Regimen The Phase 2 clinical study, led by the Sean M. Healey & AMG Center for
ALS
at
Massachusetts General Hospital
, was designed to evaluate the potential safety and efficacy of
pridopidine
, along with multiple other investigational products simultaneously, for the treatment of
ALS
. Eligible participants had El Escorial possible, probable, or definite
ALS
, symptom onset <36mo and vital capacity >50%-predicted.
Pridopidine
45 mg bid (n=121) was compared to a shared placebo (n=164). The primary endpoint was change from baseline through 24 weeks in ALSFRS-R total (Full Analysis Set, FAS). Secondary and exploratory endpoints included speech, respiration, and quality of life measurements. Prespecified and post-hoc subgroups included definite or probable
ALS
, early (<18mo symptom onset) and fast progressors (pre-baseline slope>=-1). Nominal p-values are reported. About Expanded Access for
Pridopidine
The Sean M. Healey & AMG Center for
ALS
at
Massachusetts General Hospital
has been awarded a grant from the
National Institutes of Health (NIH)
-
Neurological Disorders
and
Stroke
(NINDS) to conduct an intermediate size Expanded Access Protocol (EAP) in
ALS
in collaboration with
Prilenia Therapeutics
. The EAP made possible by this award will allow
ALS
individuals who are otherwise not eligible for participation in clinical trials of
pridopidine
to access this investigational drug. Additionally, this EAP will provide real world safety, biomarker, and clinical data in up to two hundred (200)
ALS
individuals treated with
pridopidine
for up to two (2) years, thus contributing to our understanding of the effects of
pridopidine
in a broad population. The
pridopidine
EAP will be conducted at up to 45 enrolling centers across the U.S. The enrollment phase is anticipated to start in the Spring of 2024. Additional information about
Prilenia
’s EAP policy is available on our website. About
Prilenia
Prilenia
is a clinical stage biotechnology company founded in 2018 focused on the urgent mission to develop novel therapeutics to slow the progression of
neurodegenerative diseases
and
neurodevelopmental disorders
. The initial focus of the company has been on HD and
ALS
.
Prilenia
is backed by a group of well-respected investors including: Forbion,
Morningside
,
Sands Capital
, SV Health Investors, Sectoral Asset Management,
Talisman
,
Amplitude Ventures
and the ALS Investment Fund. The Company is based in Naarden, the Netherlands, Herzliya, Israel and Waltham, Massachusetts in the U.S. For more information, visit and follow us on LinkedIn and Twitter. ©2024
Prilenia Therapeutics B.V.
For a copy of this release, visit
Prilenia
’s website at .
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机构
Prilenia Therapeutics Development Ltd.
Prilenia Therapeutics BV
The General Hospital Corp.
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