SALT LAKE CITY, Aug. 25, 2021 /PRNewswire/ -- Lipocine Inc.
(NASDAQ: LPCN), a clinical-stage biopharmaceutical company focused
on metabolic and endocrine disorders, today announced positive
topline 36-week results from its Phase 2 proof of concept
LiFT ("Liver Fat
intervention with oral Testosterone") clinical
study, NCT04134091, investigating LPCN 1144 in men with
biopsy-confirmed NASH. Currently, there are no approved treatments
for NASH, a leading cause of liver failure and liver
transplantation globally. LPCN 1144 comprises an orally delivered
prodrug of endogenous testosterone ("T").
The LiFT clinical study, a prospective, multi-center,
randomized, double-blind, placebo-controlled, multi-arm, multi-site
trial in the United States,
enrolled biopsy-confirmed hypogonadal or eugonadal male NASH
subjects with stage F1-F3 fibrosis and a NAFLD Activity Score
≥ 4 for a 36-week treatment period. Subjects with
advanced fibrosis (F2-F3) and steatohepatitis (inflammation on
liver biopsy) were also eligible. Subjects were randomized
1:1:1 to one of three arms (Treatment A, a twice daily oral dose of
142 mg testosterone equivalent; Treatment B, a twice daily oral
dose of 142 mg testosterone equivalent formulated with 238 mg of
d-alpha tocopherol equivalent; and the third arm, a twice daily
matching placebo).
The primary endpoint of the LiFT clinical study was
change in hepatic fat fraction via MRI-PDFF post 12 weeks of
treatment. Additionally, key secondary endpoints post 36 weeks of
treatment include assessment of histological change for NASH
resolution and/or fibrosis improvement. The LiFT clinical
study was not powered to assess statistical significance of any of
the secondary endpoints.
At 12 weeks, treatments with LPCN 1144 resulted in statistically
significant liver fat reduction, assessed by MRI-PDFF, meeting the
pre-specific primary endpoint of the LiFT clinical
study. Statistically significant reduction in liver fat was
observed compared to placebo: up to a mean of 9.2% absolute
reduction and a 46.8% relative reduction in liver fat.
Liver biopsies were performed at baseline ("BL") and after 36
weeks of treatment ("EOS"). Prespecified biopsy analyses include
NASH Clinical Research Network ("CRN") scoring as well as a
continuous paired ("Paired Technique") and digital technique
("Digital Technique-Fibronest"). All biopsy analyses were
performed on the same slides and the reads for the three techniques
were done independently. Analysis sets included the NASH Resolution
Set (all subjects that have BL and EOS biopsy with NASH at BL [NAS
≥4 with lobular inflammation score ≥ 1 and hepatocyte ballooning
score ≥1 at BL] (n=37)), the Biopsy Set (all subjects with baseline
and EOS biopsies (n=44)), and the Safety Set (all randomized
subjects (n=56)).
Both LPCN 1144 treatment arms met with statistical significance
the pre-specified accelerated approval regulatory endpoint of NASH
resolution with no worsening of fibrosis based on NASH CRN
scoring. Additionally, both treatment arms showed substantial
improvement of the observed NASH activity in steatosis,
inflammation and ballooning.
Key results are presented in the following table:
-Histology NASH CRN
Scoring Outcomes1
|
|
Placebo (n =
11)
|
Treatment
A
(n=13)
|
Treatment
B
(n=13)
|
NASH Resolution
responders, n (%) 2
|
1 (9%)
|
7
(54%)3
|
9,
(69%)4
|
NASH Resolution with
No Worsening of Fibrosis responders, n (%)
|
0 (0%)
|
6
(46%)3
|
9
(69%)5
|
|
1 NASH
Resolution Set
|
2
Improvement in NASH defined as improvement in ballooning or
inflammation, and no worsening of ballooning or
inflammation
|
3 p
< 0.05 vs placebo
|
4 p
< 0.01 vs placebo
|
5 p
< 0.001 vs placebo
|
Both LPCN 1144 treatment arms showed significant improvement in
NASH without worsening of fibrosis using Paired Technique, which
concurred with the NASH CRN scoring findings (per Biopsy Set; NASH
Improvement responders: Placebo – 13%, Treatment A – 60%, Treatment
B – 57%; NASH Improvement with No Worsening of Fibrosis
responders: Placebo – 13%, Treatment A – 60%, Treatment B –
57%).
The treatment effects on fibrosis improvement need confirmation
in a larger study.
Key fibrosis improvement results are presented in the following
table:
Histopathological
Assessment TechniquesX
|
|
Placebo
(n = 15)
|
Treatment
A
(n=15)
|
Treatment
B
(n=14)
|
NASH CRN:
Fibrosis Improvement ≥ 1 Stage with No Worsening of NASH,
Responders, n (%)
|
6
(40%)†
|
4 (27%)
|
2 (14%)
|
Paired
Technique: Fibrosis Improvement with No Worsening of
NASH,y Responders, n (%)
|
3 (20%)
|
6 (40%)
|
8 (57%)
|
Digital
Technique-FibroNest: Fibrosis Improvement,z
Responders, n (%)
|
5 (33%)
|
12 (80%)
|
6 (43%)
|
|
x Biopsy
Set
|
y Fibrosis
improvement on paired reads defined as a score of improvement in
fibrosis with a score of no worsening of ballooning, inflammation,
or steatosis
|
z For
Digital Reads (FibroNest - http://www.fibronest.com), improvement
defined as a decrease in parenchymal tissue normalized phenotypic
fibrosis composite score
|
† One
subject in placebo is missing NASH CRN fibrosis score and is
treated as a non-responder
|
In both treatment arms substantial reductions in markers of
liver injury compared to placebo were observed post four weeks of
treatment and were sustained through EOS. Using all available
Safety Set data, alanine aminotransferase ("ALT") decreased up to a
mean of 23.4 U/L at EOS from all group mean baseline of 51.5 U/L
and aspartate aminotransferase ("AST") decreased up to a mean of
13.3 U/L at EOS from all group mean baseline of 31.9 U/L.
Positive effects in appendicular lean mass and whole-body fat
mass, an indicator overall tissue quality, based on dual-energy
X-ray absorptiometry scans were noted in both LPCN 1144 treatment
arms.
During the 36 weeks of treatment, LPCN 1144 was well tolerated
with an overall safety profile comparable to placebo. Frequency and
severity of treatment emergent adverse events, TEAEs, in both
treatment arms were comparable to placebo. Study drug related TEAEs
were mild to moderate. Four subjects discontinued due to TEAEs in
the placebo arm vs one subject in total across the treatment arms.
Cardiovascular events were balanced among groups with hematocrit
increases averaging <2% in the treatment arms, no observed
thromboembolic events, and comparable blood pressure changes in
both treatment arms to placebo.
There were no reported cases of hepatocellular carcinoma or Drug
Induced Liver Injury ("DILI"). Weight change from baseline, GI
adverse events and PSA changes were small and comparable among
groups. Additionally, no clinically meaningful changes in lipids in
treatment groups were noted compared to placebo, and rates of pedal
edema were low and similar in all arms.
Additionally, all subjects had the option to continue with LPCN
1144 treatment through an open label extension study (NCT04685993).
The extension study will enable the collection of additional data
on LPCN 1144 for up to a total of 72 weeks of therapy.
"The extent of the LPCN 1144 efficacy results in meeting the
NASH resolution regulatory endpoint from the LiFT study are
striking with no adverse safety signal. These data strongly support
further development of this differentiated novel approach as a
treatment of NASH," said Dr. Arun Sanyal, Professor in
the Virginia Commonwealth University ("VCU") Department
of Internal Medicine and Education Core Director in
the VCU Center for Clinical and Translational
Research.
"We are delighted by the remarkable efficacy results and the
overall safety profile of LPCN 1144 in the LiFT study,
which we believe demonstrate the potential for LPCN 1144 to be the
"best in class" option for treating NASH with a discerning benefit
to risk profile as required for a chronic therapy," said
Dr. Mahesh Patel, Chairman, President and CEO of Lipocine Inc.
"Additionally, the unique benefits of LPCN 1144 in improving body
composition may fulfill an unmet medical need. We look
forward to meeting with the FDA regarding the path forward for an
accelerated approval and Phase 3 study requirements," said Dr.
Patel.
Conference Call
Management will host a conference call
and webcast today at 8:30 a.m. Eastern
time to discuss LPCN 1144 Phase 2 LiFT clinical study
key secondary endpoint topline results. To participate in the
conference call, please dial 1-877-451-6152 from the U.S. or
1-201-389-0879 from outside the U.S. In addition, following
the completion of the call, a telephone replay will be accessible
until September 1, 2021, by dialing
1-844-512-2921 from the U.S. or 1-412-317-6671 from outside the
U.S. and entering conference ID #13722634. Those interested
in listening to the conference call live via the internet may do so
by using the following
link: http://public.viavid.com/index.php?id=146385. An
archive of the webcast will also be available on the webcast page
of the Company's website for 90 days.
About NASH
NASH is a more advanced state of
non-alcoholic fatty liver disease ("NAFLD") and can progress to a
cirrhotic liver and eventually hepatocellular carcinoma/liver
cancer. Twenty-five to thirty percent of the U.S. population is
estimated to suffer from NAFLD. NASH afflicts three to twelve
percent of the U.S. population, which is a substantially large
population that lacks effective therapy. Currently, there are no
FDA approved treatments for NASH. Approximately 50% of NASH
patients are in adult males and the number of NASH cases is
projected to increase 63% from 16.5 million cases in 2015 to 27.0
million cases in 2030. NAFLD/NASH is becoming more common due to
its strong correlation with obesity and metabolic syndrome,
including components of metabolic syndrome such as diabetes,
cardiovascular disease and high blood pressure. In men, especially
with comorbidities associated with NAFLD/NASH, testosterone
deficiency has been associated with an increased accumulation of
visceral adipose tissue and insulin resistance, which could be
factors contributing to NAFLD/NASH.
About Lipocine
Lipocine Inc. is a clinical-stage
biopharmaceutical company focused on metabolic and endocrine
disorders using its proprietary drug delivery technologies.
Lipocine's clinical development pipeline includes: TLANDO, LPCN
1144, TLANDO XR, LPCN 1148, LPCN 1154, and LPCN 1107. TLANDO, a
novel oral prodrug of testosterone containing testosterone
undecanoate, has received tentative approval from the FDA for
conditions associated with a deficiency of endogenous testosterone,
also known as hypogonadism, in adult males. LPCN 1144, an oral
prodrug of bioidentical testosterone, recently completed a Phase 2
clinical study demonstrating the potential utility in the treatment
of non-cirrhotic NASH. TLANDO XR, a novel oral prodrug
of testosterone, originated and is being developed by Lipocine as a
next-generation oral testosterone product with potential for
once-daily dosing. In a phase 2 clinical evaluation when
administered as once daily or twice daily TLANDO XR met the typical
primary and secondary end points. LPCN 1148 is an oral prodrug of
bioidentical testosterone targeted for the treatment of cirrhosis.
LPCN 1107 is potentially the first oral hydroxyprogesterone
caproate product candidate indicated for the prevention of
recurrent preterm birth and has been granted orphan drug
designation by the FDA. LPCN 1154 is an oral neuro-steroid targeted
for the treatment of post-partum depression. For more
information, please visit www.lipocine.com.
Cautionary and 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 Lipocine's product candidates and related clinical
trials, the timing and completion of additional clinical trials and
studies, the potential uses and benefits of LPCN 1144 for the
treatment of NASH and fibrosis improvement, the timing of
additional data, whether LPCN 1144 will be eligible for and receive
accelerated approval from the FDA for LPCN 1144, and our product
development efforts. Investors are cautioned that all such
forward-looking statements involve risks and uncertainties,
including, without limitation, the risk that 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, 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. There can be no
assurance that we will choose, or have the ability, to conduct
Phase 3 trials with respect to LPCN 1144 and, ultimately, apply for
and receive approval from the FDA to market LPCN 1144 for the
indications described in this press release. 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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