Veru Inc. (NASDAQ: VERU), a late clinical stage biopharmaceutical
company focused on developing novel medicines for the treatment of
obesity, breast cancer and for viral induced ARDS, today announced
that the Company will advance its proprietary novel agent,
enobosarm, a selective androgen receptor modulator (SARM), into a
Phase 2b clinical trial in combination with weight-loss GLP-1
drugs, Ozempic (semaglutide), Wegovy (semaglutide), or Mounjaro
(tirzepatide) to evaluate the efficacy and the safety of enobosarm
to further increase fat loss while preventing the significant
muscle wasting that occurs with weight-loss GLP-1 drugs.
Weight loss from these medications results from the collective
loss of fat mass and lean mass (muscle and bone). Muscle is
critical for metabolism, muscle strength and physical function
(mobility) and prevention of injury (falls) especially in an older
population. According to the CDC, 42% of older adults have obesity
and could benefit from weight loss medication, but the high amount
of muscle wasting that occurs with weight-loss drugs reduces the
muscle mass to sarcopenic, or critically low amounts, which may
result in muscle weakness leading to poor balance, decreased gait
speed, mobility disability, loss of independence, falls, bone
fractures, higher hospitalizations, and increased mortality. Up to
30% of older obese patients have sarcopenic obesity, which means
they have both obesity and age-related low muscle mass at the same
time and are potentially at the greatest risk for developing
critically low muscle mass and muscle weakness and functional
limitations when taking weight-loss GLP-1 drugs.
In a study by Wilding et al. reported in The New England Journal
of Medicine, a subgroup analysis was conducted in 140 subjects from
the Obesity (STEP 1) Trial which evaluated semaglutide 2.4 mg a
week treatment compared to placebo for 68 weeks. In this analysis,
semaglutide treatment resulted in the average loss of 10.43 kg
(22.9 lbs) of fat and 6.92 kg (15.2 lbs) of muscle mass which means
that muscle loss made up 40% of the total weight lost. Similarly,
Sargeant et al. observed that treatment with GLP-1 receptor
agonists and sodium glucose cotransporter 2 inhibitors (SGLT2i)
resulted in muscle loss that made up 20-50% of the total weight
lost.
Enobosarm treatment consistently prevents loss of muscle
across 5 clinical studies (see Table)
Enobosarm is an oral, new chemical entity, new class, selective
androgen receptor targeting agent or modulator (SARM) that has
demonstrated tissue-selective, dose-dependent increases in muscle
mass (lean body mass), reduces fat mass, improves insulin
resistance, while sparing other androgenic tissue with no
masculinizing effects in women, with prostate neutral effects in
men and without increases in hematocrit. Increases in muscle mass
have resulted in improvements in muscle strength and physical
function. In preclinical studies in male and female mice, enobosarm
demonstrated the ability to prevent and treat bone loss. Enobosarm
has extensive nonclinical and clinical experience having been
evaluated in 25 separate clinical studies in approximately 1,500
subjects dosed. Five clinical studies for a total of 968 patients
measured muscle mass endpoints, including two Phase 2 clinical
studies in healthy older or sarcopenic subjects (168 subjects) and
one Phase 2b and two Phase 3 studies in subjects with muscle
wasting because of cancer (800 subjects). Muscle wasting caused by
cancer creates a “starvation state” where there is significant loss
of both lean body mass and fat mass which is similar to what has
been observed with starvation and weight loss GLP-1 drugs.
Enobosarm treatment in elderly men and postmenopausal women with
and without active muscle wasting consistently resulted in the
reduction in fat mass and significant increases in lean body mass
(muscle) with improvements muscle strength and physical
function. Enobosarm has a large safety database and was
generally well tolerated and safe in both men and women.
Table:Veru has clinical data: 5
clinical studies in 968 older subjects with and without muscle
wasting
Subjects(n=) |
Phase |
Population |
Purpose |
Muscle (LBM) |
Muscle strength/ function |
Fat Mass |
Duration |
Source |
120 (24 received enobosarm 3mg) |
2 |
Males over 60 years of age and postmenopausal women(Study
G200501) |
Dose-finding(0.1mg-3mg) |
3mg=1.25 kg increase(p< 0.001 compared to placebo) |
3mgIncrease SCP(p=0.049 compared to placebo) |
3mg=0.32 kg decrease(p=0.049 compared to placebo)Representing a
2-5% decrease of total fat mass |
12 weeks |
Dalton JTJ Cachexia Sarcopenia Muscle 2:153, 2011 and CSR |
48 (12 received enobosarm 3mg) |
2 |
Sarcopenic postmenopausal women(Study 003) |
Double-blind placebo controlled (3mg) |
3mg=1.54 kg increase(p<0.001 compared to placebo) |
Bilateral leg press3mg 21.86 lbs. increase from baseline vs placebo
1.5 lbs. increase from baseline |
Not collected |
12 weeks |
Merck study Clinical study report (on file) |
159 (41 received enobosarm 3mg) |
2b |
Muscle wasting cancer(Study G200502) |
Double-blind placebo controlled(1 and 3 mg) |
3mg = 1.3 kg increase(p=0.046 compared to baseline) |
3mg16.8 watt increase SCP.(p=0.001 compared to baseline) |
3mg= 0.76 kg decrease in total fat mass(p=0.086 compared to
placebo) |
16 weeks |
Dobs AS Lancet Oncology 14:335, 2013And CSR |
321 (160 received enobosarm 3mg) |
3 |
Lung cancer muscle wasting receiving cisplatin + taxane
chemotherapy(Study G300504) |
Double-blind placebo controlled(3mg) |
0.8 kg Increase in LBM at Day 84 (p<0.001 from baseline) Higher
mean slope of the change from baseline than placebo (p=0.0002 Day
84 and p<0.0001 Day 147) |
5.17% Increased in SCP at Day 84 vs. -1.27% in the placebo Higher
mean slope of the change from baseline (p=0.0147 at Day 84, p=0.049
at Day 147) |
Not collected |
21 weeks |
Clinical study report (on file) |
320 (159 received enobosarm 3mg) |
3 |
Lung cancer muscle wasting receiving cisplatin + nontaxane
chemotherapy(Study G300505) |
Double-blind placebo controlled(3mg) |
0.73 kg Increase in LBM Day 84 and 0.67 kg increase at Day 147
(p=0.013) Higher mean slope of the change from baseline compared to
placebo(p=0.0111 at Day 84, and p=0.0028 at Day 147) |
SCP N.S. |
Not collected |
21 weeks |
Clinical study report (on file) |
Sarcopenic= presence of low muscle mass; LBM= lean body mass; SCP=
stair climb power (Watts), power exerted in a 12-step stair climb;
CSR=clinical study report; N.S.= not significant |
|
Phase 2b Enobosarm + GLP-1 weight loss drug combination
to treat obesity and protect against muscle loss clinical study
design
Given the extensive clinical experience with enobosarm, in both
older patients and in patients with initial and ongoing muscle
wasting caused by a starvation state (cancer induced muscle
wasting), the combination of enobosarm and semaglutide or
tirzepatide therapy for weight loss or diabetes may provide
additional clinical benefit and ameliorate adverse muscle wasting
effects of GLP-1 agents. Specifically, enobosarm therapy could
augment the preferential loss of fat mass while preventing the loss
of critical muscle mass and bone mineral density. Enobosarm
treatment could also preserve or improve muscle strength and
physical function in older adults being treated with a weight loss
drug.
Veru intends to conduct a Phase 2b multicenter, double-blind,
placebo-controlled, randomized, and dose-finding obesity or
overweight clinical study in approximately 75 patients who qualify
for treatment with a GLP-1 receptor agonist, Ozempic (semaglutide),
Wegovy (semaglutide), or Mounjaro (tirzepatide), for weight loss
and are at risk for muscle loss. Patients will be randomized in a
1:1 ratio to a GLP-1 receptor agonist plus enobosarm 3mg, GLP-1
receptor agonist plus enobosarm 6mg, or a GLP-1 receptor agonist
plus placebo for 4 months. The primary endpoint of the study will
be change in total lean body mass (muscle) from baseline to 4
months. Key secondary endpoints will be change from baseline to 4
months in total fat mass, insulin resistance (HOMA-IR), and body
weight. After completing this study, participants will then
continue into a separate Bone Mineral Density (BMD) extension study
for an additional 5 months (total of 9 months) to determine the
effects of GLP-1 + enobosarm 3mg, GLP-1 + enobosarm 6mg, or GLP-1 +
placebo on bone mineral density measured by DEXA.
"While GLP-1 agonists have been very effective
in inducing substantial weight loss, there is growing concern about
the potential deleterious effects of the associated loss of muscle
and bone mass in older adults," said Dr. Dennis Villareal,
Professor of Medicine, Baylor College of Medicine and Chief,
Division of Endocrinology, Diabetes and Metabolism. "Therefore,
there is an urgent unmet need for a clinical trial to test whether
a muscle anabolic drug such as enobosarm that can effectively
preserve muscle mass during weight-loss therapy of older patients
with obesity."
“It has become apparent that the total body weight loss caused
by weight loss GLP-1 drugs is the result of not only the loss of
fat, but also the loss of significant amounts of muscle. This
muscle wasting adverse effect of GLP-1 drugs places elderly
overweight or obese patients with sarcopenic obesity at risk as
they already have low muscle mass and may develop muscle weakness,
functional limitations, mobility disability, and falls. Given the
extensive clinical experience of enobosarm, Veru has decided to
advance enobosarm into Phase 2b clinical development in combination
with GLP-1 agents (semaglutide or tirzepatide). The Phase 2b
clinical study will aim to maximize the preferential loss of fat
loss while preventing muscle wasting and bone loss caused by GLP-1
agents (semaglutide or tirzepatide),” said Mitchell Steiner, M.D.,
Chairman, President, and Chief Executive Officer of Veru. “Another
potential indication for enobosarm is for the treatment of older
obese patients that have stopped treatment with GLP-1 agent
(semaglutide or tirzepatide) and now have critically low muscle
mass. As fat will return before muscle, these elderly patients are
at risk for muscle weakness and functional limitations. The
potential market for enobosarm in combination with weight-loss
drugs is a large and growing multi-billion dollar market.”
References
Dalton JT et al. The selective androgen receptor modulator
(enobosarm) improves lean body mass and physical function in
healthy elderly men and postmenopausal women: results of double
blind, placebo -controlled Phase 2 trial. J Cachexia Sarcopenia
Muscle 2:153-161, 2011.
Dobs AS et al. Effects of enobosarm on muscle wasting and
physical function in patients with cancer: a double blind,
randomized controlled phase 2 study. Lancet Oncol 14:335-345,
2013.
Ida S et al. Effects of antidiabetic drugs on muscle mass in
type 2 diabetes mellitus. Curr Diabetes Rev 17:293-303, 2021.
Madison Muller and Bloomberg. Fortune Well: Weight-loss drugs
like Ozempic and Wegovy may be risky for older people because they
melt away all-important muscles. September 27, 2023.
Sargeant JA et al. A review of the effects of glucagon-like
peptide-1 receptor agonists and sodium-glucose cotransporter 2
inhibitors on lean body mass in humans. Endocrinol Metab
34:247-262, 2019
Villareal DT, Chode S, Parimi N, et al. Weight loss, exercise,
or both and physical function in obese older adults. N Engl J Med
3/31/2011 2011;364(13):1218-1229. doi:10.1056/NEJMoa1008234
Villareal DT, Aguirre L, Gurney AB, et al. Aerobic or Resistance
Exercise, or Both, in Dieting Obese Older Adults. N Engl J Med
5/18/2017 2017;376(20):1943-1955. doi:10.1056/NEJMoa1616338
Wennamethee SG et al. Sarcopenic Obesity and cardiometabolic
health and mortality in older adults: a growing health concern in
an aging population. Current Diabetes Reports 2023.
Wilding JPH et al. Once-weekly semaglutide in adults with
overweight or obesity. N Engl J Med 384: 989-1002, 2021.
Supplementary appendix.
About Veru Inc.Veru is a late clinical stage
biopharmaceutical company with the following programs.
Oncology program: metastatic breast cancer
The Company’s late-stage breast cancer development portfolio
comprises enobosarm, a selective androgen receptor targeting
agonist.
- Phase 3 clinical ENABLAR-2 study – enobosarm +/- abemaciclib
combination versus estrogen blocking agent (active control) as a
2nd line treatment in AR+ ER+ HER2- metastatic breast
cancer is open and active. The Company and Eli Lilly and Company
have entered into a clinical study collaboration and supply
agreement for the ENABLAR-2 study. Lilly supplies Verzenio
(abemaciclib).
Infectious disease program: viral ARDS
- Sabizabulin is an oral, first-in-class, new chemical entity,
microtubule disruptor that has dual anti-inflammatory and host
mediated antiviral properties. Veru has conducted a positive
double-blind, randomized, placebo-controlled Phase 3 COVID-19
clinical trial in 204 hospitalized moderate to severe COVID-19
patients at high risk for ARDS and death. In April 2023, the
Company reached agreement with FDA on design of the Phase 3
confirmatory COVID-19 clinical trial to evaluate sabizabulin in
hospitalized moderate to severe COVID-19 patients at high risk for
ARDS. Although the Company reached agreement with FDA for the
design of Phase 3 confirmatory COVID-19 clinical trial, the Company
met with FDA in September 2023 and reached agreement on the design
of Phase 3 study design evaluating sabizabulin 9mg for the broader
treatment of hospitalized adult patients who have any type of viral
ARDS.
- Smallpox virus: The Company had a preIND
meeting in August with FDA to discuss the development of
sabizabulin for smallpox virus. FDA agreed that the Animal Rule
pathway is acceptable for evaluating the efficacy of smallpox
virus. The Company will work with FDA to develop a plan for the
nonclinical studies that could support a smallpox indication.
Sexual health program – Urev
Veru has a commercial sexual health division called Urev that is
comprised of FC2 Female Condom® (internal condom), for the dual
protection against unplanned pregnancy and the transmission of
sexually transmitted infections which is sold in the U.S. and
globally. The Company has launched its own independent,
FC2-dedicated direct to patient telehealth and pharmacy services
portal. The Company is focused on executing new contracts with
additional telehealth partners and has internet fulfillment
pharmacy partners that provide coverage in all 50 states in the
U.S.
Forward-Looking StatementsThe statements in
this release that are not historical facts are “forward-looking
statements” as that term is defined in the Private Securities
Litigation Reform Act of 1995. Forward-looking statements in this
release include statements regarding: the planned design,
enrollment, timing, commencement, interim and full data readout
timing, scope, regulatory pathways, and results of the Company’s
current and planned clinical trials, including the planned Phase 2b
study of enobosarm with GLP-1 drugs in obesity studies, planned
Phase 3 study of sabizabulin in hospitalized adult patients with
viral induced ARDS, the Phase 3 study of enobosarm alone or in
combination with abemaciclib for the 2nd line treatment of AR+ ER+
HER2 metastatic breast cancer, the Phase 3 study of enobosarm in
bone-only non-measurable hormone receptor and HER2- metastatic
breast cancer, the Phase 3 study of sabizabulin in hospitalized
influenza patients at high risk of ARDS, and studies of sabizabulin
in smallpox virus and Ebola virus, and whether any of such studies
will meet any of its primary or secondary endpoint; whether
enobosarm will demonstrate sufficient effect in preventing muscle
wasting in patients taking GLP-1 drugs, whether enobosarm will
augment fat loss in such patients and whether enobosarm will become
a potential treatment for patients taking GLP-1 drugs or suffer
from muscle wasting generally; whether the results of the planned
sabizabulin ARDS study will be sufficient to support the submission
of an NDA and the timing of any such data reading out; whether the
Company will pursue any Phase 3 study of sabizabulin for COVID-19
alone; whether and when the Company will receive the future
installment payments of the ENTADFI purchase price or sales
milestone payments; and the outlook for growth in the Company's FC2
business through telehealth customers, our direct to patient
telehealth portal and the global public health sector. These
forward-looking statements are based on the Company’s current
expectations and subject to risks and uncertainties that may cause
actual results to differ materially, including unanticipated
developments in and risks related to: the development of the
Company’s product portfolio and the results of clinical studies
possibly being unsuccessful or insufficient to meet applicable
regulatory standards or warrant continued development; the ability
to enroll sufficient numbers of subjects in clinical studies and
the ability to enroll subjects in accordance with planned
schedules; the ability to fund planned clinical development as well
as other operations of the Company; the timing of any submission to
the FDA or any other regulatory authority and any determinations
made by the FDA or any other regulatory authority; the possibility
that as vaccines, antivirals and other treatments become widely
distributed the need for new COVID-19 or other ARDS treatment
candidates may be reduced or eliminated; government entities
possibly taking actions that directly or indirectly have the effect
of limiting opportunities for sabizabulin as a COVID-19 or other
ARDS treatment, including favoring other treatment alternatives or
imposing price controls on COVID-19 or other ARDS treatments; the
Company’s existing products, including FC2 and, if authorized,
sabizabulin, and any future products, if approved, possibly not
being commercially successful; the ability of the Company to obtain
sufficient financing on acceptable terms when needed to fund
development and operations; demand for, market acceptance of, and
competition against any of the Company’s products or product
candidates; new or existing competitors with greater resources and
capabilities and new competitive product approvals and/or
introductions; changes in regulatory practices or policies or
government-driven healthcare reform efforts, including pricing
pressures and insurance coverage and reimbursement changes; risks
relating to the Company's development of its own dedicated direct
to patient telemedicine and telepharmacy services platform,
including the Company's lack of experience in developing such a
platform, potential regulatory complexity, development costs, and
market awareness and acceptance of any telehealth platform we
develop; risks relating to our ability to increase sales of FC2
after significant declines in recent periods due to telehealth
industry consolidation and the bankruptcy of a large telehealth
customer; the Company’s ability to protect and enforce its
intellectual property; the potential that delays in orders or
shipments under government tenders or the Company’s U.S.
prescription business could cause significant quarter-to-quarter
variations in the Company’s operating results and adversely affect
its net revenues and gross profit; the Company’s reliance on its
international partners and on the level of spending by country
governments, global donors and other public health organizations in
the global public sector; the concentration of accounts receivable
with our largest customers and the collection of those receivables;
the Company’s production capacity, efficiency and supply
constraints and interruptions, including potential disruption of
production at the Company’s and third party manufacturing
facilities and/or of the Company’s ability to timely supply product
due to labor unrest or strikes, labor shortages, raw material
shortages, physical damage to the Company’s and third party
facilities, product testing, transportation delays or regulatory
actions; costs and other effects of litigation, including product
liability claims and securities litigation; the Company’s ability
to identify, successfully negotiate and complete suitable
acquisitions or other strategic initiatives; the Company’s ability
to successfully integrate acquired businesses, technologies or
products; and other risks detailed from time to time in the
Company’s press releases, shareholder communications and Securities
and Exchange Commission filings, including the Company’s Form 10-K
for the fiscal year ended September 30, 2022 and subsequent
quarterly reports on Form 10-Q. These documents are available on
the “SEC Filings” section of our website at
www.verupharma.com/investors. The Company disclaims any intent or
obligation to update these forward-looking statements.
Ozempic® and Wegovy® are trademarks owned by or licensed to Novo
Nordisk A/S, its subsidiaries, or affiliates. Mounjaro® is a
trademark owned by or licensed to Eli Lilly and Company, its
subsidiaries, or affiliates.
Investor and Media Contact:Samuel FischExecutive Director,
Investor Relations and Corporate CommunicationsEmail:
veruinvestor@verupharma.com
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