Statistically significant lower "Drug Liking"
for the 81mg and 162mg doses of oral nalbuphine vs.
butorphanol covering our clinical dose range
Company to host a conference call and webcast
today at 5:00 p.m. ET
NEW
HAVEN, Conn., Dec. 3, 2024
/PRNewswire/ -- Trevi Therapeutics, Inc. (Nasdaq: TRVI), a
clinical-stage biopharmaceutical company developing the
investigational therapy Haduvio™ (oral nalbuphine ER) for the
treatment of patients with chronic cough in idiopathic pulmonary
fibrosis (IPF) and refractory chronic cough (RCC), today announced
positive results from the human abuse potential (HAP) study of oral
nalbuphine.
The HAP study was a randomized, double-blind, double-dummy,
active and placebo controlled five-way crossover study in
recreational drug users. The study's primary endpoint was the peak
effect (Emax) for "Drug Liking" ("at this moment"),
assessed on a bi-polar, 100-point visual analog scale (VAS). The
VAS scale for this endpoint ranges from strong disliking (0) – to
neither like nor dislike (50) – to strong liking (100). Oral
nalbuphine was analyzed across three different doses (ranging from
a low dose to a supratherapeutic dose) for its "Drug Liking"
compared to the active comparator, intravenous (IV) butorphanol,
and placebo. Topline results demonstrated a statistically
significant lower "Drug Liking" for the clinical doses of oral
nalbuphine (81mg and 162mg) compared to 6mg IV butorphanol. The
supratherapeutic dose of oral nalbuphine (486mg) was numerically
lower than the 6mg IV butorphanol for "Drug Liking" but the results
were not statistically significant.
Primary Endpoint*
|
Placebo
(N=52)
|
IV butorphanol
6mg
(N=52)
|
Oral nalbuphine
81mg
(N=52)
|
Oral
nalbuphine
162mg
(N=52)
|
Oral nalbuphine
486mg
(N=52)
|
Mean Emax
for "Drug Liking"
|
51.8
|
82.3
|
71.2
|
74.5
|
81.1
|
P-value for difference
vs
butorphanol 6mg IV
|
p<0.0001
|
-
|
p<0.0001
|
p=0.0008
|
p=0.3221
|
*All analyses performed were on the Modified Completer
Population, which was prespecified in the statistical analysis plan
for the primary endpoint.
Secondary Endpoints
|
Placebo
(N=52)
|
IV butorphanol
6mg
(N=52)
|
Oral nalbuphine
81mg
(N=52)
|
Oral nalbuphine
162mg
(N=52)
|
Oral nalbuphine
486mg
(N=52)
|
Mean Emax
for "Take Drug Again"
|
53.4
|
62.8
|
71.0
|
67.3
|
64.2
|
Mean Emax
for "I Feel High"
|
3.4
|
77.6
|
35.6
|
39.3
|
59.2
|
Mean Emax
for "I Feel Good"
|
2.7
|
71.9
|
40.3
|
40.8
|
61.0
|
Secondary endpoints included pharmacodynamic markers and
patient reported outcomes, which were generally consistent with the
primary endpoint. No serious adverse events were reported in the
study.
"We're very pleased with our study results," said James Cassella, Ph.D., Chief Development Officer
of Trevi Therapeutics. "The positive butorphanol drug liking effect
versus placebo demonstrates the validity and robustness of our
study design. Our clinical program has studied doses ranging from
27mg to 162mg and we believe these results are consistent with the
known profile of nalbuphine. We look forward to reporting data from
our two ongoing chronic cough studies in IPF and RCC, two
conditions where patients continue to have a significant unmet
need."
Jack Henningfield, Ph.D., Vice
President, Research, Health Policy and Abuse Liability at Pinney
Associates added, "Nalbuphine is currently unscheduled in the U.S.
and has been for several decades. It has remained unscheduled
because of its years of experience with little evidence of
diversion, abuse, or contribution to overdose deaths. This
experience, coupled with these HAP results, continues to support
the conclusion that nalbuphine extended-release has potential to
address an important health need without the public safety risks
posed by the opioids that are often prescribed for chronic
cough."
The results of the HAP study will be included in the 8-factor
analysis of the abuse potential of nalbuphine for
nalbuphine ER that would be submitted as part of any new
drug application (NDA) submission to inform scheduling
considerations.
The Company will host a conference call and webcast to review
the topline results today, December
3rd, at 5:00 p.m.
ET. The live webcast, including audio and presentation
slides, will be accessible at the time of the meeting and can be
accessed here. To participate in the conference call by phone,
please dial (877) 870 4263 (domestic) or (412) 317 0790
(international) and ask to join the Trevi Therapeutics call. No
code is necessary for access. An archived replay of the webcast
will also be available for 30 days on the Company's website
following the event.
About the Human Abuse Potential Study for Oral
Nalbuphine
The HAP study was conducted in two parts. The
first part of the study characterized various IV butorphanol doses
in order to select a dose to be studied as the comparator. The
second part of the HAP study being reported in this release was a
randomized, double-blind, double-dummy, active and
placebo-controlled five-way crossover study. The U.S. Food and Drug
Administration, or FDA, agreed to the comparator (butorphanol),
comparator route of administration (IV to mimic intranasal
exposure), comparator dose (6mg), and nalbuphine doses. This study
compared the likeability of three doses of oral nalbuphine with 6mg
of IV butorphanol using various drug-liking scales, including the
primary endpoint, which measured the peak effect for "Drug Liking"
assessed using a bi-polar visual analog scale. Safety and
physiological measures, pharmacokinetic data, and abuse-related
adverse events were also evaluated.
About Trevi Therapeutics, Inc.
Trevi Therapeutics,
Inc. is a clinical-stage biopharmaceutical company developing the
investigational therapy Haduvio™ (oral nalbuphine extended-release)
for the treatment of chronic cough in patients with idiopathic
pulmonary fibrosis (IPF) and refractory chronic cough (RCC).
Haduvio acts on the cough reflex arc both centrally and
peripherally as a kappa agonist and a mu antagonist (KAMA), which
are opioid receptors that play a key role in controlling cough
hypersensitivity. Nalbuphine is not currently scheduled by the U.S.
Drug Enforcement Agency.
Chronic cough is highly prevalent among approximately 140,000
IPF patients in the U.S., with up to 85% of IPF patients
experiencing chronic cough. The impact of chronic cough is
significant with some IPF patients coughing up to 1,500 times per
day and may lead to worsening disease, a higher risk of
progression, death, or need for lung transplant. Chronic cough also
often leads to a decline in patients' social, physical, and
psychological quality of life. There are no approved therapies for
the treatment of chronic cough in IPF and current off-label
treatment options provide minimal benefit to patients.
Refractory chronic cough affects approximately 2-3 million
adults in the U.S. and is caused by cough reflex hypersensitivity
in both the central and peripheral nerves. It is highly disruptive
and accompanied by a wide range of complications, ranging from
urinary incontinence in females to sleep disruption and social
embarrassment that causes significant social and economic burdens
for patients and those around them. Haduvio is being developed for
the treatment of moderate to severe RCC. There are also no approved
therapies for RCC in the U.S.
Trevi intends to propose Haduvio as the trade name for oral
nalbuphine ER. Its safety and efficacy have not been evaluated by
any regulatory authority.
For more information, visit www.TreviTherapeutics.com and
follow Trevi on X (formerly Twitter) and LinkedIn.
Forward-Looking Statements
Statements contained in this press release regarding matters that
are not historical facts are "forward-looking statements" within
the meaning of the Private Securities Litigation Reform Act of
1995. Such statements are subject to risks and uncertainties and
actual results may differ materially from those expressed or
implied by such forward-looking statements. Such statements
include, but are not limited to, statements regarding Trevi's
business plans and objectives, including future plans or
expectations for Haduvio and plans and timing with respect to
clinical trials and clinical data, expectations regarding the abuse
potential of Haduvio, and other statements containing the words
"believes," "anticipates," "plans," "expects," and similar
expressions. Risks that contribute to the uncertain nature of the
forward-looking statements include: uncertainties regarding the
success, cost and timing of Trevi's product candidate development
activities and ongoing and planned clinical trials; the risk that
positive data from a clinical trial may not necessarily be
predictive of the results of later clinical trials in the same or a
different indication; uncertainties regarding Trevi's ability to
execute on its strategy; uncertainties with respect to regulatory
authorities' views as to the data from Trevi's clinical trials and
next steps in the development path for Haduvio in the United States and foreign countries,
uncertainties inherent in estimating Trevi's cash runway, future
expenses and other financial results, including Trevi's ability to
fund future operations, including clinical trials, as well as other
risks and uncertainties set forth in the quarterly report on Form
10-Q for the quarter ended September 30,
2024 filed with the Securities and Exchange Commission and
in subsequent filings with the Securities and Exchange Commission.
All forward-looking statements contained in this press release
speak only as of the date on which they were made. Trevi undertakes
no obligation to update such statements to reflect events that
occur or circumstances that exist after the date on which they were
made.
Investor Contact
Katie
Barrett
Trevi Therapeutics, Inc.
203-304-2499
k.barrett@trevitherapeutics.com
Media Contact
Rosalia
Scampoli
914-815-1465
rscampoli@marketcompr.com
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SOURCE Trevi Therapeutics, Inc.