Revive Therapeutics Ltd. (“Revive” or the “Company”) (CSE: RVV,
USA: RVVTF), a specialty life sciences company focused on the
research and development of therapeutics for medical needs and rare
disorders, is pleased to announce that following the U.S. Food
& Drug Administration (“U.S. FDA”) approval to proceed with the
Company’s Phase 3 clinical trial to evaluate the safety and
efficacy of Bucillamine in patients with mild-moderate COVID-19,
the Company has submitted its clinical trial protocol for
independent Institutional Review Board ("IRB") approval.
Additionally, the Company is exploring the FDA Expanded Access
Program, also referred to as the Compassionate Use Program, that
can provide access to the Company’s investigational drug,
Bucillamine, for people who meet the protocol criteria of the
COVID-19 study. Revive expects to have patients enrolled in
September 2020.
“We are continuing to
make strong progress in our Phase 3 clinical trial in COVID-19 and
with the submission of the Phase 3 study protocol to Advarra, a
premier IRB services company in North America, for review and
approval, it will enable us to select key clinical sites in the
U.S. and proceed with site initiation visits to allow for the
selected U.S. clinical locations to enroll patients,” said Michael
Frank, Revive’s Chief Executive Officer. “We are also exploring the
Compassionate Use Program as an alternate option for U.S. licensed
physicians to request Bucillamine for their patients who have been
diagnosed with COVID-19.”
According to the FDA,
expanded access programs provide a way for a patient to receive an
investigational drug for a serious disease or condition. These
investigational drugs are often made available when there are no
comparable or satisfactory alternative therapies to treat the
disease or condition, where patient enrollment in clinical trials
is not possible, the potential patient benefit justifies the
potential risk of treatment and when providing the investigational
drug will not interfere with clinical trials that could support the
drug’s marketing approval for the treatment indication.
About the Phase 3
Confirmatory Clinical Study
The Phase 3
confirmatory clinical study titled, “A Multi-Center, Randomized,
Double-Blind, Placebo-Controlled Study of Bucillamine in Patients
with Mild-Moderate COVID-19”, will enroll up to 1,000 patients that
will be randomized 1:1:1 to receive Bucillamine 100 mg three times
a day (“TID”), Bucillamine 200 mg TID or placebo TID for up to 14
days. The primary objective is to compare the frequency of
hospitalization or death in patients with mild-moderate COVID-19
receiving Bucillamine therapy with those receiving placebo.
The primary endpoint is the proportion of patients meeting a
composite endpoint of hospitalization or death from the time of the
first dose through Day 28 following randomization. Efficacy
will be assessed by comparing clinical outcomes (death or
hospitalization), disease severity using the 8-category NIAID COVID
ordinal scale, supplemental oxygen use, and progression of COVID‑19
between patients receiving standard-of-care plus Bucillamine (high
dose and/or low dose) and patients receiving standard-of-care plus
placebo. Safety will be assessed by reported pre-treatment
adverse events and treatment-emergent adverse events (including
serious adverse events and adverse events of special interest),
laboratory values (hematology and serum chemistry), vital signs
(heart rate, respiratory rate, and temperature), and peripheral
oxygen saturation.
An interim analysis
will be performed by an Independent Data and Safety Monitoring
Board (“DSMB”) after 210 patients have been treated and followed up
for 28 days after randomization. The better performing
Bucillamine dose at the interim analysis will be selected and
patients will then be randomized 2:1 to the selected Bucillamine
dose or placebo. Additional interim analyses will be performed
after 400, 600, and 800 patients have reached this same
post-treatment timepoint. The independent DSMB will actively
monitor interim data for the ongoing safety of patients and will
recommend continuation, stopping or changes to the conduct of the
study based on the interim analysis reports.
The Company is not
making any express or implied claims that its product has the
ability to eliminate or cure COVID-19 (SARS-2 Coronavirus) at this
time.
Scientific Rationale
of Bucillamine for COVID-19
Preclinical and
clinical studies have demonstrated that reactive oxygen species
contribute to the destruction and programmed cell death of
pulmonary epithelial cells.1 N-acetyl-cysteine (NAC) has been shown
to significantly attenuate clinical symptoms in respiratory viral
infections in animals and humans, primarily via donation of thiols
to increase antioxidant activity of cellular glutathione2,3,4,5.
Bucillamine (N-(mercapto-2-methylpropionyl)-l-cysteine) has a
well-known safety profile and is prescribed in the treatment of
rheumatoid arthritis in Japan and South Korea for over 30 years.
Bucillamine, a cysteine derivative with two thiol groups, has been
shown to be 16 times more potent as a thiol donor in vivo than NAC
6. The drug is non-toxic with high cellular permeability. The basis
of the clinical study will analyze if Bucillamine has the
potential, via increasing glutathione activity and other
anti-inflammatory activity, to lessen the destructive consequences
of SARS-CoV2 infection in the lungs and attenuate the clinical
course of COVID-19.
About Revive Therapeutics
Ltd.
Revive is a life sciences company focused on the
research and development of therapeutics for infectious diseases
and rare disorders, and it is prioritizing drug development efforts
to take advantage of several regulatory incentives awarded by the
FDA such as Orphan Drug, Fast Track, Breakthrough Therapy and Rare
Pediatric Disease designations. Currently, the Company is exploring
the use of Bucillamine for the potential treatment of infectious
diseases, with an initial focus on severe influenza and COVID-19.
With its recent acquisition of Psilocin Pharma Corp., Revive is
advancing the development of Psilocybin-based therapeutics in
various diseases and disorders. Revive’s cannabinoid pharmaceutical
portfolio focuses on rare inflammatory diseases and the company was
granted FDA orphan drug status designation for the use of
Cannabidiol (CBD) to treat autoimmune hepatitis (liver disease) and
to treat ischemia and reperfusion injury from organ
transplantation. For more information, visit
www.ReviveThera.com.
For more information, please contact:
Michael Frank Chief Executive Officer Revive Therapeutics Ltd.
Tel: 1 888 901 0036 Email: mfrank@revivethera.com
Website: www.revivethera.com Neither the Canadian
Securities Exchange nor its Regulation Services Provider have
reviewed or accept responsibility for the adequacy or accuracy of
this release.
Cautionary Statement
This press release contains ‘forward-looking
information’ within the meaning of applicable Canadian securities
legislation. These statements relate to future events or future
performance. The use of any of the words “could”, “intend”,
“expect”, “believe”, “will”, “projected”, “estimated” and similar
expressions and statements relating to matters that are not
historical facts are intended to identify forward-looking
information and are based on Revive’s current belief or assumptions
as to the outcome and timing of such future events. Forward looking
information in this press release includes information with respect
to the Offering, including the intended use of proceeds.
Forward-looking information is based on reasonable assumptions that
have been made by Revive at the date of the information and is
subject to known and unknown risks, uncertainties, and other
factors that may cause actual results or events to differ
materially from those anticipated in the forward-looking
information. Given these risks, uncertainties and assumptions, you
should not unduly rely on these forward-looking statements. The
forward-looking information contained in this press release is made
as of the date hereof, and Revive is not obligated to update or
revise any forward-looking information, whether as a result of new
information, future events or otherwise, except as required by
applicable securities laws. The foregoing statements expressly
qualify any forward-looking information contained herein. Reference
is made to the risk factors disclosed under the heading “Risk
Factors” in the Company’s annual MD&A for the fiscal year ended
June 30, 2019, which has been filed on SEDAR and is available under
the Company’s profile at www.sedar.com.
References
1. S Ye et al,
Inhibition of Reactive Oxygen Species Production Ameliorates
Inflammation Induced by Influenza A Viruses via Upregulation of
SOCS1 and SOCS3., American Society for Microbiology. 2015
Mar;89(5):2672-2683).
2. L. Carati et al,
Attenuation of influenza-like symptomatology and improvement of
cell-mediated immunity with long-term N-acetylcysteine treatment.,
Eur Respir J. 1997 Jul;10(7):1535-41).
3. M Mata et al,
N-acetyl-L-cysteine (NAC) inhibit mucin synthesis and
pro-inflammatory mediators in alveolar type II epithelial cells
infected with influenza virus A and B and with respiratory
syncytial virus (RSV)., Biochem Pharmacol. 2011
Sep;82(5):548-55.
4. D Ungheri et al,
Protective effect of n-acetylcysteine in a model of influenza
infection in mice., Int J Immunopathol Pharmacol. 2000
Sep-Dec;13(3):123-128.
5. RH Zhang et al,
N-acetyl-l-cystine (NAC) protects against H9N2 swine influenza
virus-induced acute lung injury., Int Immunopharmacol. 2014
Sep;22(1):1-8).
6. LD Horwitz, Bucillamine: a potent thiol donor
with multiple clinical applications, Cardiovasc Drug
Rev. 2003 Summer;21(2):77-90).
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