- Lipocine to receive $11 million
license fee
- Up to $259 million in development
and commercial sales milestones
- Tiered royalties on net sales of licensed products up to
18%
- Commercialization of TLANDO transitions to Verity Pharma
effective Feb.1 2024
- Lipocine retains all rights for territories outside
the United States and Canada, and all non-TRT rights globally
SALT
LAKE CITY, Jan. 18, 2024 /PRNewswire/ -- Lipocine
Inc. (NASDAQ: LPCN), a biopharmaceutical company focused on
treating Central Nervous System (CNS) disorders, Gordon Silver
Limited and Verity Pharmaceuticals, Inc. (Verity Pharma) today
announced that they have entered into an exclusive licensing
agreement under which Verity Pharma will market TLANDO® in
the United States and, if
approved, in Canada. TLANDO is the first and only oral
testosterone replacement therapy (TRT) option approved by the US
Food and Drug Administration (FDA) that does not require dose
titration. The agreement also provides Verity Pharma with the
U.S. and Canadian rights to develop and commercialize LPCN 1111
(TLANDO XR), a next generation, once daily oral product candidate
for TRT.
Under the terms of the agreement, Lipocine will receive
from Verity Pharma a license fee of $11
million with an initial payment of $2.5 million which was received on signing of the
License Agreement, $5 million to be
paid on February 1, 2024,
$2.5 million to be paid no later than
January 1, 2025, and $1 million to be paid no later than January 1, 2026. Lipocine will be
entitled to receive up to $259
million in development and sales-based commercial milestone
payments, as well as tiered royalty payments at rates ranging from
12% up to 18% on net sales of TLANDO franchise products.
Under the agreement, Verity Pharma will be responsible for
regulatory and marketing obligations in the U.S. and Canada, and all further development.
Lipocine retains all rights to the TLANDO franchise for territories
outside the U.S. and Canada, and
all rights to non-TRT indications globally.
"We are very pleased to enter this license agreement with Verity
Pharma. Men's health is one of Verity Pharma's areas of focus and
Verity Pharma's sales force has existing relationships with men's
health prescribers. Verity Pharma is highly motivated and has the
capabilities and expertise to successfully grow the TLANDO
franchise without interruption in patient access to TLANDO," said
Dr. Mahesh Patel, President and Chief Executive Officer of
Lipocine. "This transaction will further enable Lipocine's
strategy to focus on developing treatments for CNS disorders and to
add value to our non-core assets."
TRT is a large and growing market with ~8M annual prescriptions
in the U.S. and ~650,000 in Canada.
Raymond James acted as financial
advisor to Lipocine on this transaction.
About TLANDO
TLANDO is approved by the FDA as a testosterone replacement
therapy ("TRT") in adult males indicated for conditions associated
with a deficiency or absence of endogenous testosterone: primary
hypogonadism (congenital or acquired) and hypogonadotropic
hypogonadism (congenital or acquired). It was developed using
Lipocine's proprietary Lip'ral drug delivery technology
platform.
For full prescribing information, please visit
www.TLANDO.com.
IMPORTANT SAFETY INFORMATION
TLANDO (testosterone undecanoate) capsules, for oral use,
CIII
Initial U.S. Approval: 1953
IMPORTANT SAFETY INFORMATION
WARNING: BLOOD PRESSURE INCREASES (See Boxed Warning on
Product Label for more information)
TLANDO can cause blood pressure (BP) increases that can increase
the risk of major adverse cardiovascular events (MACE), including
non-fatal myocardial infarction, non-fatal stroke and
cardiovascular death with greater risk in patients with established
cardiovascular disease or risk factors for cardiovascular
disease.
Before initiating TLANDO, consider the patient's baseline
cardiovascular risk and ensure blood pressure is adequately
controlled.
Three weeks after initiating therapy monitor for and treat
new-onset hypertension or exacerbations of pre-existing
hypertension.
Re-evaluate whether the benefits of TLANDO outweigh its risks in
patients who develop cardiovascular risk factors or cardiovascular
disease on treatment. Due to this risk, use TLANDO only for the
treatment of men with hypogonadal conditions associated with
structural or genetic etiologies.
TLANDO INDICATIONS AND USAGE
TLANDO (testosterone undecanoate) is indicated for testosterone
replacement therapy in adult males for conditions associated with a
deficiency or absence of endogenous testosterone.
Primary hypogonadism (congenital or acquired)
Hypogonadotropic hypogonadism (congenital or acquired)
LIMITATIONS OF USE
Safety and efficacy of TLANDO in males less than 18 years old
have not been established.
CONTRAINDICATIONS
TLANDO is contraindicated in:
Patients with carcinoma of the breast or known or suspected
carcinoma of the prostate.
Women who are pregnant. Testosterone can cause virilization of
the female fetus when administered to a pregnant woman.
Known hypersensitivity to testosterone undecanoate or any of
TLANDO's ingredients.
Men with hypogonadal conditions, such as "age-related
hypogonadism", that are not associated with structural or genetic
etiologies. The efficacy of TLANDO has not been established for
these conditions, and TLANDO can increase BP that can increase the
risk of MACE.
WARNINGS AND PRECAUTIONS
Increase in Blood Pressure: In Study 18-001, TLANDO increased
systolic BP after 4 months of treatment by an average of 4.3 mmHg
based on ambulatory blood pressure monitoring (ABPM) and 4.8 mmHg
from baseline based on blood pressure cuff measurements [see
Adverse Reactions (6.1)].
These BP increases can increase the risk of major adverse
cardiovascular events (MACE), with greater risk in patients with
established cardiovascular disease or risk factors for
cardiovascular disease.
In some patients, the increase in BP with TLANDO may be too
small to detect but can still increase the risk for MACE.
Before initiating TLANDO, consider the patient's baseline
cardiovascular risk and ensure blood pressure is adequately
controlled. Check BP approximately 3 weeks after initiating TLANDO
and periodically thereafter. Treat new-onset hypertension or
exacerbations of pre-existing hypertension. Re-evaluate whether the
benefits of continued treatment with TLANDO outweigh its risks in
patients who develop cardiovascular risk factors or cardiovascular
disease.
Polycythemia: Increases in hematocrit levels, reflective of
increases in red blood cell mass, may require discontinuation of
TLANDO. Check hematocrit prior to initiating TLANDO. Evaluate
hematocrit approximately every 3 months during the first year of
treatment, and then every 6 months thereafter while the patient is
taking TLANDO. If hematocrit becomes elevated, stop TLANDO until
hematocrit decreases to an acceptable concentration. If TLANDO is
restarted and again causes hematocrit to become elevated, stop
TLANDO permanently. An increase in red blood cell mass may increase
the risk of thromboembolic events.
Cardiovascular Risk: Long term clinical safety trials have not
been conducted to assess the cardiovascular outcomes of
testosterone replacement therapy in men. To date, epidemiologic
studies and randomized controlled trials have been inconclusive for
determining the risk of major adverse cardiovascular events (MACE),
such as non-fatal myocardial infarction, non-fatal stroke, and
cardiovascular death, with the use of testosterone compared to
non-use. Some studies, but not all, have reported an increased risk
of MACE in association with use of testosterone replacement therapy
in men.
TLANDO can cause BP increases that can increase the risk of
MACE. Patients should be informed of this possible risk when
deciding whether to use or to continue to use TLANDO.
Worsening of Benign Prostatic Hyperplasia (BPH) and Potential
Risk of Prostate Cancer: Patients with BPH treated with androgens
are at an increased risk for worsening of signs and symptoms of
BPH. Monitor patients with BPH for worsening signs and symptoms.
Patients treated with androgens may be at increased risk for
prostate cancer. Evaluate patients for prostate cancer, including
measurement of prostate specific antigen (PSA), prior to initiating
and during treatment with androgens.
Venous Thromboembolism: There have been post marketing reports
of venous thromboembolic events, including deep vein thrombosis
(DVT) and pulmonary embolism (PE), in patients using testosterone
replacement products such as TLANDO. Evaluate patients who report
symptoms of pain, edema, warmth, and erythema in the lower
extremity for DVT and those who present with acute shortness of
breath for PE. If a venous thromboembolic event is suspected,
discontinue TLANDO and initiate appropriate workup and
management.
Abuse of Testosterone and Monitoring of Serum Testosterone
Concentrations: Testosterone has been subject to abuse, typically
at doses higher than recommended for the approved indication and in
combination with other anabolic androgenic steroids. Anabolic
androgenic steroid abuse can lead to serious cardiovascular and
psychiatric adverse reactions.
If testosterone abuse is suspected, check serum testosterone
concentrations to ensure they are within therapeutic range.
However, testosterone levels may be in the normal or subnormal
range in men abusing synthetic testosterone derivatives. Counsel
patients concerning the serious adverse reactions associated with
abuse of testosterone and anabolic androgenic steroids. Conversely,
consider the possibility of testosterone and anabolic androgenic
steroid abuse in suspected patients who present with serious
cardiovascular or psychiatric adverse events.
Not for Use in Women: Due to lack of controlled studies in women
and the potential for virilizing effects, TLANDO is not indicated
for use in women. Potential for Adverse Effects on Spermatogenesis:
With large doses of exogenous androgens, including TLANDO,
spermatogenesis may be suppressed through feedback inhibition of
pituitary follicle-stimulating hormone (FSH) possibly leading to
adverse effects on semen parameters including sperm count. Patients
should be informed of this possible risk when deciding whether to
use or to continue to use TLANDO.
Hepatic Adverse Effects: Prolonged use of high doses of orally
active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been
associated with serious hepatic adverse effects (peliosis hepatis,
hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis
hepatis can be a life-threatening or fatal complication. Long-term
therapy with intramuscular testosterone enanthate has produced
multiple hepatic adenomas. TLANDO is not a 17 alpha-alkyl
androgen and is not known to produce hepatic adverse effects
associated with 17-alpha-alkyl androgens.
Nonetheless, patients should be instructed to report any signs
or symptoms of hepatic dysfunction (e.g., jaundice). If these
occur, promptly discontinue TLANDO while the cause is
evaluated.
Edema: Androgens, including TLANDO, may promote retention of
sodium and water. Edema, with or without congestive heart failure,
may be a serious complication in patients with preexisting cardiac,
renal, or hepatic disease [see Adverse Reactions (6.1)]. In
addition to discontinuation of the drug, appropriate work up and
management of edema may be required.
Sleep Apnea: The treatment of hypogonadal men with testosterone
products may potentiate sleep apnea in some patients, especially
those with risk factors such as obesity or chronic lung
diseases.
Gynecomastia: Gynecomastia may develop and persist in patients
being treated for hypogonadism.
Lipid Changes: Changes in serum lipid profile may require dose
adjustment of lipid lowering drugs or discontinuation of
testosterone therapy. Monitor the lipid profile periodically after
starting testosterone therapy.
Hypercalcemia: Androgens, including TLANDO, should be used with
caution in cancer patients at risk of hypercalcemia (and associated
hypercalciuria). Monitor serum calcium concentrations periodically
in these patients.
Decreased Thyroxine-binding Globulin: Androgens, including
TLANDO, may decrease concentrations of thyroxin-binding globulins,
resulting in decreased total T4 serum concentrations and increased
resin uptake of triiodothyronine (T3) and thyroxine (T4). Free
thyroid hormone concentrations remain unchanged, however, and there
is no clinical evidence of thyroid dysfunction.
Increases in Prolactin: Increases in serum prolactin have been
reported in patients treated with TLANDO in clinical trials.
Evaluate serum prolactin levels prior to initiating treatment with
TLANDO. Re-evaluate serum prolactin levels 3 to 4 months after
starting treatment. If serum prolactin remains elevated,
discontinue TLANDO.
ADVERSE REACTIONS
The safety of TLANDO was evaluated in 2 clinical studies in a
total of 233 men.
Study 18-001: 138 hypogonadal males were treated with TLANDO 225
mg twice daily with morning and evening meals for approximately 4
months.
Study 16-002: 95 hypogonadal males were treated with TLANDO 225
mg twice daily with morning and evening meals for approximately 24
days.
The most commonly reported adverse reactions (≥ 2%) were:
increased blood prolactin, hypertension, increased hematocrit,
upper respiratory tract infection, weight increased, headache, and
musculoskeletal pain.
DRUG INTERACTIONS
Insulin: Changes in insulin sensitivity or glycemic control may
occur in patients treated with androgens. In diabetic patients, the
metabolic effects of androgens may decrease blood glucose and,
therefore, insulin requirements.
Oral Anticoagulants: Changes in anticoagulant activity may be
seen with androgens. Frequent monitoring of INR and prothrombin
time may be necessary in patients taking anticoagulants, especially
at the initiation and termination of androgen therapy.
Corticosteroids: The concurrent use of testosterone with
corticosteroids may result in increased fluid retention and should
be monitored cautiously, particularly in patients with cardiac,
renal or hepatic disease.
Drugs that May Also Increase Blood Pressure: Some prescription
drugs and nonprescription analgesic and cold medications can
increase blood pressure. Concomitant administration of these
medications with TLANDO may lead to additional increases in blood
pressure.
USE IN SPECIFIC POPULATIONS
Pregnancy: TLANDO is contraindicated in pregnant women and not
indicated for use in females. Testosterone is teratogenic and may
cause fetal harm when administered to a pregnant woman based on
data from animal studies (see Data) and its mechanism of action.
Exposure of a female fetus to androgens may result in varying
degrees of virilization. In animal developmental studies, exposure
to testosterone in utero resulted in hormonal and behavioral
changes in offspring and structural impairments of reproductive
tissues in female and male offspring. These studies did not meet
current standards for nonclinical development toxicity studies.
Lactation: TLANDO is not indicated for use in females.
Females and Males of Reproductive Potential: During treatment
with large doses of exogenous androgens, including TLANDO,
spermatogenesis may be suppressed through feedback inhibition of
the hypothalamic-pituitary-testicular axis. Reduced fertility is
observed in some men taking testosterone replacement therapy. The
impact on fertility may be irreversible. Testicular atrophy,
subfertility, and infertility have also been reported in men who
abuse anabolic androgenic steroids.
Pediatric Use: The safety and effectiveness of TLANDO in
pediatric patients less than 18 years old have not been
established. Improper use may result in acceleration of bone age
and premature closure of epiphyses.
Geriatric Use: There have not been sufficient numbers of
geriatric patients in controlled clinical studies with TLANDO to
determine whether efficacy or safety in those over 65 years of age
differs from younger subjects. Of the 95 patients enrolled in Study
16-002, the 24-day major safety and effectiveness study utilizing
TLANDO, 16 (16.8%) were over 65 years of age. Additionally,
there is insufficient long-term safety data in geriatric patients
utilizing TLANDO to assess the potentially increased risk of
cardiovascular disease and prostate cancer.
Geriatric patients treated with androgens may also be at risk
for worsening of signs and symptoms of BPH and hypertension.
DRUG ABUSE AND DEPENDENCE
TLANDO contains testosterone undecanoate, a Schedule III
controlled substance.
Abuse and misuse of testosterone are seen in male and female
adults and adolescents. Testosterone, often in combination with
other anabolic androgenic steroids may be abused by athletes and
bodybuilders.
Serious adverse reactions have been reported in individuals who
abuse anabolic androgenic steroids and include cardiac arrest,
myocardial infarction, hypertrophic cardiomyopathy, congestive
heart failure, cerebrovascular accident, hepatotoxicity, and
serious psychiatric manifestations, including major depression,
mania, paranoia, psychosis, delusions, hallucinations, hostility
and aggression.
The following adverse reactions have also been reported in men:
transient ischemic attacks, convulsions, hypomania, irritability,
dyslipidemias, testicular atrophy, subfertility, and
infertility.
The following additional adverse reactions have been reported in
women: hirsutism, virilization, deepening of voice, clitoral
enlargement, breast atrophy, male-pattern baldness, and menstrual
irregularities.
The following adverse reactions have been reported in male and
female adolescents: premature closure of bony epiphyses with
termination of growth, and precocious puberty.
Withdrawal symptoms can be experienced upon abrupt
discontinuation in patients with addiction. Withdrawal symptoms
include depressed mood, major depression, fatigue, craving,
restlessness, irritability, anorexia, insomnia, decreased libido,
and hypogonadotropic hypogonadism. Drug dependence in individuals
using approved doses for approved indications has not been
documented.
For more information, call 1-844-996-7833.
Please see full Prescribing Information, including Boxed Warning
and Medication Guide.
About TLANDO XR
TLANDO XR (also known as LPCN 1111) is a next-generation, novel
ester prodrug of testosterone comprised of testosterone
tridecanoate (TT) which uses Lipocine's proprietary delivery
technology to enhance solubility and improve systemic absorption.
Lipocine has successfully completed a Phase 2b dose finding study in hypogonadal men. Results
suggested that the primary objectives were met, including
identifying the dose expected to be tested in a planned Phase 3
study that would be required for FDA approval.
About Verity Pharma
Verity Pharma is a specialty pharmaceutical company focused on
delivering meaningful solutions to healthcare professionals and
their patients..
Verity Pharma works with best-in-class global pharmaceutical
manufacturing partners to ensure that product quality and
availability is a constant deliverable. The company is also
committed to supporting programs, initiatives, and organizations
that help improve health, expand research opportunities and promote
education within the healthcare community. Learn more
at www.veritypharma.com.
About Lipocine
Lipocine is a biopharmaceutical company leveraging its
proprietary technology platform to augment therapeutics through
effective oral delivery to develop differentiated 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, a novel androgen receptor agonist prodrug for oral
administration 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, LPCN1154, for rapid relief of postpartum depression,
LPCN 1148, for the management of decompensated cirrhosis, and LPCN
1144, our candidate for treatment of non-cirrhotic NASH.
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 Verity Pharma's development
and commercialization of TLANDO and TLANDO XR, the amount of the
license fee, milestone payments, and royalty payments we will
ultimately receive, Verity Pharma's ability to grow the TLANDO
franchise, our product development efforts, the application of our
proprietary platform in developing new treatments for CNS
disorders, our product candidates and related clinical trials, our
development of and filing of a NDA with the FDA for LPCN 1148, and
the potential uses and benefits of our product candidates.
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 have sufficient
capital to complete the development processes for our product
candidates, 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.