Adial Pharmaceuticals, Inc. (NASDAQ: ADIL; ADILW)
(“Adial” or the “Company”), a clinical-stage biopharmaceutical
company focused on developing therapies for the treatment and
prevention of addiction and related disorders, announces that
greater than 50% of patients expected to complete the ONWARD™ Phase
3 trial evaluating AD04 as a therapeutic agent for the treatment of
Alcohol Use Disorder (AUD) in persons with certain target genotypes
related to the serotonin transporter and receptor genes have
completed the full, 24-week, treatment period.
ONWARD is a 24-week, multicenter, randomized,
double-blind, placebo-controlled, parallel group, pivotal Phase 3
clinical trial to evaluate the efficacy, safety and tolerability of
AD04 in patients with AUD and selected polymorphisms in the
serotonin transporter and receptor genes.
The intended primary endpoint for analysis of
efficacy is the change from baseline in the monthly number of heavy
drinking days (HDDs) during the last 8 weeks (weeks 16-24) of the
24-week treatment period, where heavy drinking is defined as the
consumption of 5 or more drinks/day for men and 4 or more
drinks/day for women.
Drinking levels are self-reported using the
timeline follow-back (TLFB) method. The TLFB method is a daily
calendar for alcohol consumption and employs memory aids to prompt
recall. The TLFB has been used extensively in pharmacotherapy
trials for AUD and other substance abuse disorders. Baseline is the
4-week period prior to the screening visit. For each subsequent
clinic visit, alcohol consumption is recorded as the number of
drinks per day.
Patients have been randomized based on a
one-to-one (placebo-to-AD04) ratio, so that approximately 50% of
enrolled patients will be in the placebo group and 50% in the AD04
group. Both placebo and active clinical trial material were
manufactured in two batches of equal amounts and are light-yellow,
oval tablets for oral administration with each tablet weighing
approximately 80 mg. Placebo and active tablets are
indistinguishable from each other. The active tablets have 0.33 mg
of AD04’s active ingredient, Ondansetron, in place of a similar
volume of excipient (i.e., starch) in the placebo. They have been
packaged in blister-packs of 18 tablets, which allows for 7-days of
dosing plus 2-days extra to allow for flexibility in appointment
scheduling. During packaging, the clinical trial material was coded
so that neither the Company, the doctors, nor the patients can
determine whether a package contains placebo or active tablets
(i.e., double-blinding).
Adverse events are monitored by the Company’s
Chief Medical Officer; Crown CRO (the contract research
organization running ONWARD), and the trial’s Data Monitoring
Committee. Clinical trial material can be unblinded in the event
one of these safety reviewers determines unblinding is necessary to
ensure the safety of any particular trial patient on a case-by case
basis. To date, no situations have arisen where it was determined
unblinding would be warranted, and therefore, no trial patients
have had their dosing unblinded to determine if they were taking
placebo or active tablets.
ONWARD is being conducted in 25 clinical sites
in six countries in Scandinavia and Central and Eastern Europe:
Sweden, Finland, Poland, Latvia, Bulgaria and Croatia. The
Coordinating Principal Investigator is Professor Hannu E.R. Alho,
Emeritus Professor of Addiction Medicine at the University of
Helsinki.
Patients are genetically screened prior to
enrollment in the ONWARD trial so that only genetically positive
patients are enrolled. A total of 1216 people were genetically
screened with 403 showing genetic positivity for the AD04 target
genotypes (i.e., 33%).
Behavioral therapy (i.e., counseling) is
administered to all trial patients so that the placebo or drug will
be an adjunct therapy to behavioral therapy. This was required by
the regulatory authorities because behavioral therapy is considered
the standard of care. A successful approval would therefore likely
result in a label stating that AD04 should be administered in
combination with behavioral therapy. This would be expected to be
similar to psychiatric drugs, such as anti-depressants. The Company
agreed that use of a standardized counseling protocol in the trial
would be important and the Company’s Chief Medical Officer provided
training for all clinical sites to administer the behavioral
therapy. All clinical sites have been certified for using this
protocol.
In order to qualify for enrollment in ONWARD, in
addition to having the genotype, patients had to meet the following
additional requirements (i.e., inclusion criteria), among
others:
- Male or female over the age of 18
years old;
- Qualify as having AUD under the
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition
(DSM-5) [Criteria can be found here];
- Have experienced 6 or more heavy
drinking days in the previous 4 weeks;
- Have not been abstinent for more
than 14 days in the previous 4 weeks; and
- Expression of a desire to reduce or
stop alcohol consumption (i.e., are treatment seeking).
Patients meeting the above inclusion criteria
were rejected for enrollment in ONWARD based on the following key
criteria (i.e., exclusion criteria), among others:
- Withdrawal symptoms requiring
medical intervention at either the screening of baseline
visit;
- Diagnosis of any of the following
concomitant psychiatric disorders: non-treated, unstable
schizophrenia, bipolar disorder, other psychotic disorder during
the lifetime of the patient;
- Recent (within last 12 months)
diagnosis of a major depressive disorder, post-traumatic stress
disorder, panic disorder or eating disorder;
- Current or recent treatment with
antipsychotics or antidepressants medications, which can have an
effect on serotonin receptor or transporter actions, or opiate
antagonists (e.g., naltrexone, Vivitrol®, Selincro®), glutamate
antagonists (e.g., acamprosate), anticonvulsants (e.g.,
topiramate), serotonin reuptake inhibitors (e.g., fluoxetine),
serotonin antagonists (e.g., buspirone), other antidepressants
(e.g., tricyclic antidepressants or monoamine oxidase inhibitors),
dopamine antagonists (e.g., haloperidol), and disulfiram
(Antabuse®);
- Clinically significant untreated
and unstable illness, for example, hepatic or renal insufficiency,
or a cardiovascular, pulmonary, gastrointestinal, endocrine,
neurological, infectious, neoplastic, or metabolic
disturbance;
- Clinically abnormal ECG or
significantly abnormal vital signs;
- Clinically significant hepatic
disease; and
- Positive pregnancy test (females
only).
The ONWARD Phase 3 clinical trial commenced with
the opening of a site in Finland in February 2020, and 302 patients
have been enrolled. Enrollment was closed on August 30, 2021
immediately after the 302nd patient was randomized for placebo or
active treatment and completed the first treatment visit. Since
each trial patient undergoes approximately 24 weeks of treatment,
the last patient should complete dosing in February 2022. Each
patient receives a follow-up call approximately 4 weeks after
completing of the full treatment cycle to collect additional safety
and tolerability information.
As of the week ending September 24th, 120
patients had successfully completed their participation in the
trial, 60 patients had discontinued participation in the trial
prior to completion, and 122 patients are still being dosed in the
trial. As stated above, the last of these patients is expected to
complete dosing in February 2022. Patient retention rates continue
to exceed projections.
As each ONWARD trial site discharges its last
patient, the Company will work expeditiously to resolve any
outstanding data queries at each site so that it can be closed upon
the last follow-up call 4 weeks later. Once the last patient
completes his or her final dose, which is expected in February
2022, the Company anticipates closing the last site within 6 weeks.
Following closure of the last site, the database containing all the
information will be “locked,” meaning it can no longer be changed;
the trial will be unblinded so that it will be known for each
patient whether the patient received placebo or active tablets; and
data analysis will commence by the Company’s outside statisticians.
Results will be released expeditiously, likely within a few weeks
of the last site closure.
Dr. Bankole Johnson, Adial’s Chief Medical
Officer, commented, “Having overseen more than 20 AUD and other
addiction related clinical trials during the course of my career, I
am invigorated by the rapid progress of our ONWARD Phase 3 trial.
Just last month we announced we had achieved full enrollment and
now we have taken 50% of patients expected to complete the trial
through their full trial dosing range of 24-weeks. We remain
encouraged by the trial retention rate, which has exceeded our
expectations. Importantly, we remain on target to complete all
patient dosing in the first quarter of 2022. I would like to thank
our team, our CRO and the clinical investigators for their hard
work in efficiently advancing this important trial. I look forward
with anticipation to trial data with great expectations.”
William Stilley, Adial’s Chief Executive
Officer, stated, “Following years of research and clinical trials,
as we move closer to completion of our ONWARD Phase 3 trial of AD04
for the treatment of AUD, we are highly confident that our
genetically targeted approach may provide significant promise for
those suffering from this devastating disease, which contributes to
the annual deaths of more than 3 million people and costs the U.S.
economy approximately $250 billion annually. This trial is
especially timely given the dramatic increase in the number of
persons suffering with this disorder, exacerbated in significant
part due to the ongoing effects of the pandemic. In ONWARD, we
anticipate demonstrating a favorable safety profile with AD04 with
a low occurrence of any side effects and we are optimistic we will
meet our primary endpoint. With the ease of oral administration by
patients, we believe those suffering from AUD will be more likely
to complete their treatment regimen in the real world as compared
with current therapies, which are all known to have side effects
that we believe, on balance, are more significant than those
expected to be demonstrated by AD04. I extend a heartfelt thank you
to our entire trial team and our patients that are bringing us
closer to a new day in the treatment of alcohol use disorder.”
About Adial Pharmaceuticals,
Inc.
Adial Pharmaceuticals is a clinical-stage
biopharmaceutical company focused on the development of treatments
for addictions. The Company’s lead investigational new drug
product, AD04, is a genetically targeted, serotonin-3 receptor
antagonist, therapeutic agent for the treatment of Alcohol Use
Disorder (AUD) and is currently being investigated in the Company’s
landmark pivotal ONWARD™ Phase 3 clinical trial for the potential
treatment of AUD in patients with certain target genotypes, which
are identified using the Company’s proprietary companion diagnostic
genetic test. A Phase 2b clinical trial of AD04 for the treatment
of AUD showed promising results in reducing frequency of drinking,
quantity of drinking and heavy drinking (all with statistical
significance), and no overt safety concerns (there were no
statistically significant serious adverse events reported). AD04 is
also believed to have the potential to treat other addictive
disorders such as Opioid Use Disorder, gambling, and obesity. The
Company is also developing adenosine analogs for the treatment of
pain and other disorders. Additional information is available at
www.adialpharma.com.
About the Landmark ONWARD™ Pivotal Phase
3 Clinical Trial
The ONWARD trial is a 24-week, multicenter,
randomized, double-blind, placebo-controlled, parallel group,
pivotal Phase 3 clinical trial to evaluate the efficacy, safety and
tolerability of AD04 in patients with Alcohol Use Disorder (AUD)
and selected polymorphisms in the serotonin transporter and
receptor genes. Patients are genetically screened prior to
enrollment in the ONWARD trial so that only genetically positive
patients are enrolled. The primary endpoint for analysis of
efficacy is the change from baseline in the monthly number of heavy
drinking days during the last 8 weeks of the 24-week treatment
period. ONWARD is currently being conducted in 25 clinical sites in
six countries in Scandinavia and Central and Eastern Europe
(Sweden, Finland, Poland, Latvia, Bulgaria and Croatia). The
Coordinating Principal Investigator is Professor Hannu E.R. Alho,
Emeritus Professor of Addiction Medicine at the University of
Helsinki.
Forward Looking Statements
This communication contains certain
"forward-looking statements" within the meaning of the U.S. federal
securities laws. Such statements are based upon various facts and
derived utilizing numerous important assumptions and are subject to
known and unknown risks, uncertainties and other factors that may
cause actual results, performance or achievements to be materially
different from any future results, performance or achievements
expressed or implied by such forward-looking statements. Statements
preceded by, followed by or that otherwise include the words
"believes," "expects," "anticipates," "intends," "projects,"
"estimates," "plans" and similar expressions or future or
conditional verbs such as "will," "should," "would," "may" and
"could" are generally forward-looking in nature and not historical
facts, although not all forward-looking statements include the
foregoing. The forward-looking statements include statements
regarding completion of the ONWARD Phase 3 trial in Q1 2022, the
last patient dosing being completed in February 2022, the Company’s
genetically targeted approach providing significant promise for
those suffering from AUD, demonstrating a favorable safety profile
with AD04 with a low occurrence of any side effects, meeting the
primary endpoint, patients suffering from AUD being more likely to
complete their treatment regimen in the real world as compared with
current therapies due to the ease of oral administration by
patients, side effects of current treatments being more significant
than those expected to be demonstrated by AD04, and the potential
of AD04 to treat other addictive disorders such as opioid use
disorder, gambling, and obesity. Any forward-looking statements
included herein reflect our current views, and they involve certain
risks and uncertainties, including, among others, our ability to
complete the ONWARD Phase 3 trial in Q1 2022 and complete dosing of
the last patient in February 20222, and achieve desired results and
benefits as expected, including meeting the primary endpoint and a
favorable safety and low-side effect profile, our ability to obtain
regulatory approvals for commercialization of product candidates or
to comply with ongoing regulatory requirements, regulatory
limitations relating to our ability to promote or commercialize our
product candidates for specific indications, acceptance of product
candidates in the marketplace and the successful development,
marketing or sale of products, our ability to maintain our license
agreements, the continued maintenance and growth of our patent
estate, our ability to establish and maintain collaborations, our
ability to obtain or maintain the capital or grants necessary to
fund its research and development activities, and our ability to
retain our key employees or maintain our Nasdaq listing. These
risks should not be construed as exhaustive and should be read
together with the other cautionary statement included in our Annual
Report on Form 10-K for the year ended December 31, 2020,
subsequent Quarterly Reports on Form 10-Q and current reports on
Form 8-K filed with the Securities and Exchange Commission. Any
forward-looking statement speaks only as of the date on which it
was initially made. We undertake no obligation to publicly update
or revise any forward-looking statement, whether as a result of new
information, future events, changed circumstances or otherwise,
unless required by law.
Contact:Crescendo Communications,
LLC David
Waldman / Natalya
Rudman Tel:
212-671-1021 Email:
adil@crescendo-ir.com
Adial Pharmaceuticals (NASDAQ:ADIL)
Historical Stock Chart
From Mar 2024 to Apr 2024
Adial Pharmaceuticals (NASDAQ:ADIL)
Historical Stock Chart
From Apr 2023 to Apr 2024