- Met primary endpoint: treatment with LPCN 1148 increased L3
skeletal muscle index (L3-SMI) relative to placebo (P
<0.01)
- Fewer hepatic encephalopathy (HE) events of grade >1 in the
LPCN 1148 treatment arm relative to placebo (P < 0.05)
- More patients on LPCN 1148 reported symptom improvement
compared to placebo (P < 0.05)
- LPCN 1148 was well-tolerated, with AE rates and severities
similar to placebo
- Conference call and webcast today at 8:30am ET
SALT
LAKE CITY, July 27,
2023 /PRNewswire/ -- Lipocine Inc. (NASDAQ: LPCN), a
biopharmaceutical company focused on treating Central Nervous
System (CNS) disorders by leveraging its proprietary platform to
develop differentiated products, today announced positive topline
results from a Phase 2 clinical study of LPCN 1148. LPCN 1148 is an
oral candidate under development for the clinical management of
cirrhosis. Lipocine plans to meet with the FDA to discuss a
development path to NDA filing.
"We are delighted with the positive results from our Phase 2
study," said Dr. Mahesh Patel, President and CEO of Lipocine
Inc. "Managing cirrhosis is a significant unmet medical need
with a strong pharmaco-economic rationale. We believe LPCN 1148 is
a compelling development opportunity; if approved, we believe it
has potential to be the standard of care in managing advanced
cirrhosis."
This Phase 2 proof of concept study is an ongoing randomized
placebo-controlled study in sarcopenic male patients with cirrhosis
on the liver transplant waitlist. Twenty-nine patients were
randomized 1:1 to receive either LPCN 1148 or matching placebo for
24 weeks. At Week 24, the open-label extension stage of the study
begins; during this stage all patients receive LPCN 1148. The
study's primary endpoint was a change in L3-SMI at week 24. L3-SMI
estimates whole body skeletal muscle mass and is the standard for
sarcopenia assessment in cirrhosis. Secondary endpoints included
rates of decompensation events including hepatic encephalopathy,
and participant-reported change in symptoms using the PGI-C
scale.
All LPCN 1148-treated patients completed Week 24 (n=15), whereas
ten of fourteen placebo patients completed Week 24. All LPCN
1148-treated patients had at least one evaluable post-baseline CT
scan and are therefore part of the modified intent to treat (mITT)
analysis; ten placebo-treated patients had an evaluable
post-baseline CT. As prespecified, L3-SMI analysis was performed on
the mITT population (n=25), with the last evaluable post-baseline
observation carried forward (LOCF).
Results
Primary endpoint: LPCN 1148 treatment resulted in a
significant increase in L3-SMI at Week 24 compared to placebo, as
shown in Table 1 below.
Table 1. Change in
L3-SMI at Week 24
|
Timepoint
|
LPCN
1148
(n=15)
|
Placebo
(n=10)
|
P-value
|
Change from
Baseline
|
Vs.
Placebo
|
Baseline
(cm2/m2)
|
47.8 (1.8)
|
45.8 (2.3)
|
N/A
|
NS
|
Week 24 CFB
(cm2/m2)
|
3.62 (0.93)
|
- 0.74
(1.14)
|
<0.001
|
0.007
|
Data are LS mean (SE). CFB, Change from Baseline
|
Clinical Decompensation Events: 1148-treated
patients experienced significantly fewer cases of hepatic
encephalopathy > Grade 1 compared to placebo, despite the two
treatment groups having similar number of patients with a medical
history of hepatic encephalopathy.
Table 2: Major
Decompensation Events During the First 24 Weeks of the Study
|
|
LPCN 1148
(n=15)
|
Placebo
(n=14)
|
Total decompensation
events
|
7
|
10
|
Total
decompensation events > Grade 1
|
6
|
10
|
Hepatic
Encephalopathy
|
3
|
6
|
HE >
Grade 1 *
|
2
|
6
|
Recurrence
of HE > Grade 1
|
1
|
6
|
Time to
first recurrence of HE >
Grade 1
(days)
|
115
|
39**
|
Decompensation events include HE, ascites, variceal bleeding,
spontaneous bacterial peritonitis
Recurrence of HE: Medical history of HE + HE
events during the study
*P < 0.05 vs placebo
** Mean value
|
Consistent with the American Association for the Study of Liver
Disease (AASLD) statement, if a patient recovers a significant
amount of liver function and muscle mass from the time they had
bouts of HE, the patient may be able to stop standard HE
therapy. Our study results support the concept that
improvement in sarcopenia improves clinical outcomes.
As assessed by PGI-C, patients who received active treatment
reported significant improvement in symptoms as early as Week 4,
which persisted through Week 24. LPCN 1148 patients showed a
significant increase in hemoglobin and trended towards resolution
of anemia, improvement of ascites, and reduced total number of days
hospitalized. CT scans also suggest improved muscle quality and
reduced visceral and subcutaneous fat with LPCN 1148 therapy.
LPCN 1148 was well-tolerated, with adverse event (AE) rates and
severities similar to placebo; no mortality was noted in the LPCN
1148 treatment group. Rates of diarrhea and nausea were low and
similar in both groups. There were no cases of drug-induced liver
injury.
Dr. Arun J. Sanyal, MD,
Interim Chair, Division of Gastroenterology, Hepatology and
Nutrition, Virginia Commonwealth
University, commented, "Sarcopenia and frailty are major
markers of poor outcomes for patients with end-stage liver
disease. It is very exciting to see proof of concept that
correction of sarcopenia by LPCN 1148 safely improved muscle mass,
functional status and quality of life as well as reduced days in
the hospital compared to placebo. This demonstrates for the first
time that correcting sarcopenia improves many clinically
significant issues for this very sick population and could provide
a better bridge to transplant and quality of life for those who are
not transplant candidates. I look forward to larger studies
to further confirm the efficacy and safety of LPCN 1148 that was
observed in this study."
Dr. Jennifer Lai, MD, MBA, study
principal investigator, Professor of Medicine, UCSF, and a
practicing general/transplant hepatologist and board-certified
Physician Nutrition Specialist, added, "All of these patients had
advanced liver disease awaiting liver transplant which predisposes
them to losing muscle mass. The fact that those who received LPCN
1148 gained muscle mass in a relatively short time is remarkable.
The signals toward improved clinical outcomes, such as hospitalized
days and rates of hepatic encephalopathy, are scientifically
plausible effects of having higher muscle mass and are quite
promising."
Cirrhosis is an end stage liver disease of varying etiologies
such as alcoholic liver disease, chronic hepatitis, nonalcoholic
fatty liver disease and primary cholangitis. Complications of
cirrhosis include decompensation events such as hepatic
encephalopathy due to systemic ammonia buildup, variceal bleeding,
and ascites, which require frequent hospitalizations. Poor
Quality of Life (QOL) is common while waiting for a liver
transplant. Although there is a limited supply of donor livers,
transplant is the only cure for end-stage cirrhosis. Hepatic
encephalopathy (HE) is a frequent complication and one of the most
debilitating manifestations of liver disease, severely affecting
the lives of patients and their caregivers. Furthermore, cognitive
impairment associated with cirrhosis results in utilization of more
health care resources in adults than other manifestations of liver
disease. LPCN 1148 comprises testosterone dodecanoate, a unique
androgen receptor agonist. It is targeted as a differentiated
intervention option with a novel multimodal mechanism of action to
elicit potential benefits in management of cirrhosis and associated
comorbidities of cirrhosis.
About the Phase 2 study
This multi-center study
enrolled and dosed a total of 29 patients across 8 centers in the
US. The primary objective was to evaluate the efficacy of 24 weeks
of LPCN 1148 treatment in cirrhotic men with sarcopenia. The
secondary objective was to evaluate the safety and tolerability of
LPCN 1148. Baseline characteristics, including age, disease
etiology baseline L3-SMI, and other comorbidities were generally
well-balanced between groups. Overall, the average baseline Model
for End-Stage Liver Disease (MELD) score was 16.8, and 97% of
patients had previously experienced at least one clinical
decompensation event. Sarcopenia, or low muscle mass, was assessed
by computed tomography (CT) scan; total skeletal muscle area was
measured by CT scan at the third lumbar vertebra and normalized by
subject height (L3-SMI, L3-skeletal muscle index). Patients had
study visits every four weeks, with CTs performed at Week 12 and
Week 24. Patients with a variety of cirrhosis etiologies were
eligible. During the study there were no restrictions on standard
of care medications, procedures, or other interventions.
Further details on the study design, including inclusion and
exclusion criteria, can be found on Clinicaltrials.gov
(NCT04874350).
Conference Call and Webcast
Lipocine management will
host a conference call and webcast with slides beginning at
8:30 a.m. Eastern Time today to
discuss the Phase 2 clinical study results and answer
questions. To participate via telephone, please dial
1-877-451-6152 or 1-201-389-0879 (ex-U.S. toll dial-in number)
using the conference ID 13740396. Participants can also click
the Call me™ link,
https://callme.viavid.com/viavid/?callme=true&passcode=13738729&h=true&info=company&r=true&B=6,
for instant telephone access to the event. The Call me™ link
will be made active 15 minutes prior to scheduled start time. The
webcast is available to view here and also at www.lipocine.com. It
will be available for replay for 180 days.
About Lipocine
Lipocine is a biopharmaceutical company
leveraging its proprietary technology platform to augment
therapeutics through effective oral delivery to develop products
for CNS disorders. Lipocine has drug candidates in development as
well as drug candidates for which we are exploring partnering. Our
drug candidates represent enablement of differentiated, patient
friendly oral delivery options for favorable benefit to risk
profile which target large addressable markets with significant
unmet medical needs.
Lipocine's clinical development candidates include: LPCN 1154,
oral brexanolone, for the potential treatment of postpartum
depression, LPCN 2101 for the potential treatment of epilepsy and
LPCN 1148, an oral prodrug of bioidentical testosterone targeted
for the management of symptoms associated with liver cirrhosis.
Lipocine is exploring partnering opportunities for LPCN 1107,
our candidate for prevention of preterm birth, LPCN 1148, for the
management of decompensated cirrhosis, LPCN 1144, our candidate for
treatment of non-cirrhotic NASH, and LPCN 1111, a once-a-day
therapy candidate for testosterone replacement therapy (TRT).
TLANDO, a novel oral prodrug of testosterone containing
testosterone undecanoate developed by Lipocine, is approved by the
FDA for conditions associated with a deficiency of endogenous
testosterone, also known as hypogonadism, in adult males. For
more information, please visit www.lipocine.com.
Forward-Looking Statements
This release contains "forward-looking statements" that are
made pursuant to the safe harbor provisions of the Private
Securities Litigation Reform Act of 1995 and include statements
that are not historical facts regarding our product development
efforts, our product candidates and related clinical trials, our
strategic plans for developing products to treat CNS disorders, our
ability to monetize non-core product candidates, including through
entering into partnering arrangements, the application of our
proprietary platform in developing new treatments for CNS
disorders, the timing and completion of regulatory reviews,
outcomes of clinical trials of our product candidates, the
potential uses and benefits of our product candidates, the
potential uses and benefits of LPCN 1148, the timing of and our
ability to make any NDA filing relating to LPCN 1148, . Investors
are cautioned that all such forward-looking statements involve
risks and uncertainties, including, without limitation, the risks
that we may not be successful in developing product candidates to
treat CNS disorders, we may not be able to enter into partnerships
or other strategic relationships to monetize our non-core assets,
the FDA will not approve any of our products, risks related to our
products, expected product benefits not being realized, clinical
and regulatory expectations and plans not being realized, new
regulatory developments and requirements, risks related to the FDA
approval process including the receipt of regulatory approvals and
our ability to utilize a streamlined approval pathway for LPCN
1154, the results and timing of clinical trials, patient acceptance
of Lipocine's products, the manufacturing and commercialization of
Lipocine's products, and other risks detailed in Lipocine's filings
with the SEC, including, without limitation, its Form 10-K and
other reports on Forms 8-K and 10-Q, all of which can be obtained
on the SEC website at www.sec.gov. Lipocine assumes no
obligation to update or revise publicly any forward-looking
statements contained in this release, except as required by
law.
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SOURCE Lipocine Inc.