Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical
company (the “Company”), today announced topline results from a
Week 24 interim analysis of 160 subjects in its 48-week MOMENTUM
Phase 2 obesity trial of pemvidutide along with the results of the
12-week Phase 1b safety trial of pemvidutide in subjects with
obesity or overweight and type 2 diabetes.
MOMENTUM Phase 2 Obesity Trial – Week 24
Interim Analysis
The MOMENTUM Phase 2 obesity trial is being
conducted at 30 sites across the U.S., with Dr. Louis Aronne,
Professor of Metabolic Research and Professor of Clinical Medicine,
Weill Cornell Medicine, a leading authority in obesity and obesity
clinical trials, serving as the Principal Investigator. The trial
was designed to enroll approximately 320 subjects with obesity or
overweight with at least one co-morbidity and without diabetes.
Subjects were randomized 1:1:1:1 to 1.2 mg, 1.8 mg, 2.4 mg
pemvidutide or placebo administered weekly for 48 weeks in
conjunction with diet and exercise. A pre-specified interim
analysis was conducted after 160 subjects completed 24 weeks of
treatment. Subjects in the interim analysis had a demographic
composition similar to the full study population previously
announced, with a median age of approximately 48 years, a median
body mass index of approximately 36 kg/m2, and a median body weight
of approximately 100 kg. Approximately 75% of subjects were female,
and approximately 20% of subjects were of Hispanic ethnicity.
At Week 24, subjects receiving pemvidutide
achieved mean weight losses of 7.3%, 9.4% and 10.7% at the 1.2 mg,
1.8 mg, and 2.4 mg doses, respectively, with the placebo group
experiencing a mean weight loss of 1.0% (p < 0.001 at all three
doses vs placebo, efficacy estimand using a mixed model of repeated
measures [MMRM] analysis). An impact of baseline body weight was
observed, where subjects with baseline body weight less than or
equal to 115 kg (75% of the study population) achieved mean weight
losses of 8.2%, 10.6%, 11.9% and 0.8% at the 1.2 mg, 1.8 mg, 2.4 mg
and placebo groups, respectively (p < 0.001 at all three doses
vs placebo). Approximately 50% of subjects achieved 10% or more
weight loss and approximately 20% of subjects achieved 15% or more
weight loss at Week 24 at the 1.8 mg and 2.4 mg doses. Robust
reductions in waist circumference (a measure of visceral fat) and
serum lipids were also observed, and clinically meaningful
reductions in blood pressure were achieved without meaningful
increases in heart rate. Glucose homeostasis was also maintained,
with no significant changes in fasting glucose or HbA1c.
Regarding safety, upper GI events of nausea and
vomiting comprised the majority of AEs. These events were
predominantly mild and moderate in severity, dose-related and
similar in frequency to those observed in prior trials of
pemvidutide. Rates of lower GI AEs including diarrhea and
constipation were notably low. This AE profile was observed in the
absence of dose titration at the 1.2 mg and 1.8 mg doses and with a
limited 4-week dose titration at the 2.4 mg dose. One subject
(2.4%) experienced a serious adverse event of nausea and vomiting
requiring rehydration at the 2.4 mg dose. Treatment discontinuation
rates were 28.2% in subjects receiving placebo and 24.0% in
subjects receiving pemvidutide. The majority of placebo
discontinuations were due to withdrawal of consent, while
approximately half of the withdrawals across the pemvidutide dose
groups were attributed to GI AEs. These discontinuations occurred
almost entirely in the first 16 weeks of treatment. The protocol
did not allow for dose reduction due to intolerability as employed
in other incretin trials.
“The weight loss achieved was impressive and
bodes well for the effects that could be achieved at the completion
of 48 weeks of therapy,” said Louis Aronne, M.D., Sanford I. Weill
Professor of Metabolic Research and Professor of Clinical Medicine,
Weill Cornell Medicine, and a paid scientific advisory board member
for Altimmune, Inc. “I believe that the reductions in total and LDL
cholesterol, blood pressure and waist circumference have the
potential to be compelling product attributes, if approved, for
patients with risk factors for cardiovascular disease. The impact
of baseline weight, which was likewise observed with semaglutide
above 115 kg, suggests that higher doses could be an effective
strategy in the population with more severe degrees of
obesity.”
“We regard these results as extremely
promising,” said Vipin K. Garg, Ph.D., President and Chief
Executive Officer of Altimmune. “The ability to achieve robust
reductions in body weight, waist circumference, blood pressure, and
serum lipids, together with the previously demonstrated
best-in-class effects on liver fat reduction, suggest that
pemvidutide has the potential to be an important treatment option
for patients with obesity, especially those who are at risk for
liver disease, dyslipidemia and related conditions.” Dr. Garg
added, “We believe that the 1.2 mg and 1.8 mg doses used without
dose titration would be attractive options for primary care
physicians and that we have the opportunity to improve further upon
the profile of pemvidutide by utilizing higher doses in patients
with more severe degrees of obesity, by allowing dose reduction and
by employing a more prolonged titration for doses higher than 1.8
mg in our future trials. We look forward to completing our 48-week
MOMENTUM obesity trial in the fourth quarter of 2023 and initiating
a Phase 2 biopsy NASH trial in mid-2023.”
MOMENTUM Week 24 Interim
Analysis—Summary of Efficacy Findings
Primary Endpoint: Body weight |
Placebo(n=39) |
1.2 mg(n=40) |
1.8 mg(n=40) |
2.4 mg(n=41) |
∆ Body weight, all subjects |
%, LSM (SE)1 |
-1.0 (0.8) |
-7.3 (0.8)*** |
-9.4 (0.8)*** |
-10.7 (0.9)*** |
Impact of Baseline Body Weight on Efficacy |
Placebo(n=28) |
1.2 mg(n=30) |
1.8 mg(n=31) |
2.4 mg(n=31) |
∆ Body weight, subjects with baseline weight ≤ 115 kg |
%, LSM (SE)1 |
-0.8 (1.0) |
-8.2 (1.1)*** |
-10.6 (1.1)*** |
-11.9 (1.1)*** |
|
Responder Analyses |
Placebo(n=28) |
1.2 mg(n=33) |
1.8 mg(n=33) |
2.4 mg(n=26) |
% Subjects w/ ≥5% weight loss |
% |
25.0% |
66.7%** |
66.7%*** |
84.6%**** |
% Subjects w/ ≥10% weight loss |
% |
0.0% |
30.3%** |
48.5%**** |
50.0%**** |
% Subjects w/ ≥15% weight loss |
% |
0.0% |
6.1% |
18.2%* |
23.1%* |
|
|
|
|
|
|
Secondary Endpoints |
Placebo(n=39) |
1.2 mg(n=40) |
1.8 mg(n=40) |
2.4 mg(n=41) |
∆ Waist circumference |
cm, LSM (SE)1 |
-4.0 (1.5) |
-8.2 (1.5)** |
-8.8 (1.5)*** |
-10.2 (1.6)*** |
∆ Total cholesterol |
mg/dl. mean (SE)2 |
-2.5 (4.7) |
-13.0 (4.7)** |
-14.5 (4.9)*** |
-16.5 (5.1)*** |
∆ LDL cholesterol |
-1.1 (7.9) |
-5.5 (7.9) |
-10.3 (8.3) |
-12.7 (8.5) |
∆ Triglycerides |
-3.3 (9.4) |
-25.1 (9.6)** |
-14.4 (9.9) |
-25.0 (10.3)** |
∆ Systolic BP |
mm Hg, LSM (SE)1 |
-0.5 (2.6) |
-2.9 (2.5) |
-3.1 (2.7) |
-5.5 (2.8) |
∆ Diastolic BP |
0.5 (1.6) |
-0.1 (1.5) |
-1.4 (1.6) |
-1.8 (1.7) |
∆ Heart rate |
bpm, LSM (SE)1 |
-2.4 (1.9) |
0.0 (1.8) |
1.0 (1.9) |
0.6 (2.0) |
1 MMRM, 2ANCOVA, *p < .05; ** p < 0.05, *** p < 0.001,
****p < 0.0001 compared with placebo
MOMENTUM Week 24 Interim
Analysis—Summary of Safety Findings
|
Placebo(n=39) |
1.2 mg(n=40) |
1.8 mg(n=40) |
2.4 mg(n=41) |
Adverse events (AEs) |
Serious AEs |
n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
1 (2.4%)1 |
Discontinuations due to AE |
n (%) |
1 (2.6%) |
3 (7.5%) |
4 (10.0%) |
11 (26.8%) |
Gastrointestinal AEs |
Nausea AEs |
Mild, n (%) |
2 (5.1%) |
5 (12.5%) |
9 (22.5%) |
12 (29.3%) |
Moderate, n (%) |
0 (0.0%) |
3 (7.5%) |
13 (32.5%) |
9 (22.0%) |
Severe, n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
1 (2.4%) |
Vomiting AEs |
Mild, n (%) |
0 (0.0%) |
0 (0.0%) |
2 (5.0%) |
5 (12.2%) |
Moderate, n (%) |
0 (0.0%) |
2 (5.0%) |
3 (7.5%) |
4 (9.8%) |
Severe, n (%) |
0 (0.0%) |
0 (0.0%) |
1 (2.5%) |
1 (2.4%) |
Diarrhea AEs |
Mild, n (%) |
0 (0.0%) |
3 (7.5%) |
2 (5.0%) |
4 (9.8%) |
Moderate, n (%) |
2 (5.1%) |
0 (0.0%) |
0 (0.0%) |
2 (4.9%) |
Constipation AEs |
Mild, n (%) |
0 (0.0%) |
3 (7.5%) |
1 (2.5%) |
5 (12.2%) |
Moderate, n (%) |
2 (5.1%) |
2 (5.0%) |
1 (2.5%) |
1 (2.4%) |
Glycemic Control |
Fasting glucose |
Baseline, mg/dL |
mean (SD) |
96.1 (9.8) |
97.0 (12.2) |
103.1 (12.1) |
100.3 (12.9) |
Week 24, mg/dL |
mean (SD) |
97.7 (11.4) |
96.0 (11.2) |
103.9 (14.4) |
102.5 (18.4) |
HbA1c |
Baseline, % |
mean (SD) |
5.5 (0.4) |
5.6 (0.3) |
5.5 (0.4) |
5.5 (0.4) |
Week 24, % |
mean (SD) |
5.5 (0.3) |
5.5 (0.3) |
5.6 (0.5) |
5.6 (0.5) |
1 Rehydration for nausea and vomiting
Phase 1b Type 2 Diabetes Safety Trial
The Phase 1b trial, which was conducted to
evaluate the safety profile of pemvidutide in subjects with
overweight or obesity and type 2 diabetes, was comprised of 54
subjects randomized 1:1:1:1 to 1.2 mg, 1.8 mg, 2.4 mg pemvidutide
or placebo administered weekly for 12 weeks. No caloric
restrictions or lifestyle interventions were employed. Subjects
were required to be 18-65 years of age with BMI ≥ 28 kg/m2 and type
2 diabetes on a stable regimen of diet and exercise, metformin with
absent or mild GI symptoms, or SGLT-2 therapy for at least 3
months.
Subjects receiving pemvidutide achieved mean
weight losses of 4.4%, 6.1% and 7.7% at the 1.2 mg, 1.8 mg, and 2.4
mg doses, respectively, over only 12 weeks of treatment, with the
placebo group experiencing a mean weight gain of 0.8% (efficacy
estimand using MMRM analysis).
Glucose homeostasis was maintained throughout
the 12 weeks of treatment, with no significant changes in fasting
glucose or HbA1c and no hyperglycemic AEs. No SAEs were observed in
patients treated with pemvidutide. Rates of GI AEs were low, and
there were no AEs leading to study discontinuation.
Phase 1b Type 2 Diabetes Safety
Trial—Summary of Efficacy Findings
Body weight |
Placebo(n=14) |
1.2 mg(n=14) |
1.8 mg(n=13) |
2.4 mg(n=13) |
∆ Body weight, all subjects |
%, LSM (SE)1 |
+0.8 (0.7) |
-4.4 (1.1)*** |
-6.1 (1.6)*** |
-7.7 (1.4)*** |
1 MMRM, *** p < 0.001 compared with
placebo
Phase 1b Type 2 Diabetes Safety
Trial—Summary of Safety Findings
|
Placebo(n=14) |
1.2 mg(n=14) |
1.8 mg(n=13) |
2.4 mg(n=13) |
Glycemic Control |
Fasting glucose |
Baseline, mg/dL |
mean (SD) |
140.9 (41.6) |
132.6 (25.0) |
124.9 (31.0) |
128.2 (22.8) |
Week 24, mg/dL |
mean (SD) |
140.4 (45.4) |
132.0 (32.8) |
126.2 (15.7) |
140.6 (28.7) |
HbA1c |
Baseline, % |
mean (SD) |
6.6 (1.3) |
6.5 (1.0) |
6.6 (0.7) |
6.9 (0.7) |
Week 24, % |
mean (SD) |
7.0 (1.4) |
6.5 (0.5) |
6.7 (0.8) |
7.0 (0.6) |
Adverse events (AEs) |
Serious AEs |
n (%) |
1 (7.1%)2 |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
Discontinuations due to AE |
n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
Hyperglycemia AEs |
n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
Gastrointestinal AEs |
Nausea AEs |
Mild, n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
2 (15.4%) |
Moderate, n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
1 (7.7%) |
Vomiting AEs |
Mild, n (%) |
0 (0.0%) |
0 (0.0%) |
1 (7.7%) |
1 (7.7%) |
Moderate, n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
Diarrhea AEs |
Mild, n (%) |
0 (0.0%) |
0 (0.0%) |
1 (7.7%) |
0 (0.0%) |
Moderate, n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
Constipation AEs |
Mild, n (%) |
1 (7.1%) |
0 (0.0%) |
0 (0.0%) |
2 (15.4%) |
Moderate, n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
2 Cervical radiculopathy
About PemvidutidePemvidutide is
a novel, investigational, peptide-based GLP-1/glucagon dual
receptor agonist in development for the treatment of obesity and
NASH. Activation of the GLP-1 and glucagon receptors is believed to
mimic the complementary effects of diet and exercise on weight
loss, with GLP-1 suppressing appetite and glucagon increasing
energy expenditure. Glucagon is also recognized as having direct
effects on hepatic fat metabolism, leading to rapid reductions in
levels of liver fat. Pemvidutide incorporates the
EuPort™ domain, a proprietary technology that increases its
serum half-life for weekly dosing while likely slowing the entry of
pemvidutide into the bloodstream, which may improve its
tolerability.
Conference Call
InformationAltimmune management will host a conference
call and webcast with a slide presentation presented by Dr. Scott
Harris, Chief Medical Officer, and Dr. Louis Aronne, Principal
Investigator, beginning at 8:30 am E.T. today. Following the
conclusion of the call, the webcast will be available for replay on
the Investor Relations page of the Company’s website at
www.altimmune.com. The Company has used, and intends to continue to
use, the IR portion of its website as a means of disclosing
material non-public information and for complying with disclosure
obligations under Regulation FD.
Conference Call Details: |
|
Date: |
Tuesday, March 21 |
Time: |
8:30 am Eastern Time |
Webcast: |
To listen, the conference call will be webcast live on
Altimmune’s Investor Relations website at
https://ir.altimmune.com/investors. |
Dial-in: |
To participate or dial-in, register here to receive the dial-in
numbers and unique PIN to access the call. |
|
|
About AltimmuneAltimmune is a
clinical-stage biopharmaceutical company focused on the development
of novel peptide-based therapeutics for the treatment of obesity
and liver diseases. The Company’s lead product candidate,
pemvidutide (formerly ALT-801), is a GLP-1/glucagon dual receptor
agonist that is being developed for the treatment of obesity and
NASH. In addition, Altimmune is developing HepTcell™, an
immunotherapeutic designed to achieve a functional cure for chronic
hepatitis B. For more information, please visit
www.altimmune.com.
Follow @Altimmune, Inc. on
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Forward-Looking Statement
Any statements made in this press release
relating to future financial or business performance, conditions,
plans, prospects, trends, or strategies and other financial and
business matters, including without limitation, the timing of key
milestones for the Company’s clinical assets, such as
the completion of the Company’s 48-week MOMENTUM obesity trial
and initiation of the Phase 2 biopsy NASH trial of pemvidutide, and
the prospects for regulatory approval, commercializing or selling
any product or drug candidates, are forward-looking statements
within the meaning of the Private Securities Litigation Reform Act
of 1995. In addition, when or if used in this press release, the
words “may,” “could,” “should,” “anticipate,” “believe,”
“estimate,” “expect,” “intend,” “look forward,” “plan,”
“potential,” “predict” and similar expressions and their variants,
as they relate to the Company may identify forward-looking
statements. The Company cautions that these forward-looking
statements are subject to numerous assumptions, risks, and
uncertainties, which change over time. Important factors that may
cause actual results to differ materially from the results
discussed in the forward looking statements or historical
experience include risks and uncertainties, including risks
relating to: potential impacts such as delays in regulatory review,
manufacturing and supply chain interruptions, access to clinical
sites, enrollment, adverse effects on healthcare systems and
disruption of the global economy; the impact of base line
characteristics, such as body weight, and demographics on the
success of future trials; the reliability of the results of trials
relating to human safety and possible adverse effects resulting
from the administration of the Company’s product candidates; the
Company’s ability to manufacture clinical trial materials on the
timelines anticipated; and the success of future product
advancements, including the success of future clinical trials.
Further information on the factors and risks that could affect the
Company's business, financial conditions and results of operations
are contained in the Company’s filings with the U.S. Securities and
Exchange Commission (the “SEC”), including under the heading “Risk
Factors” in the Company’s annual report on Form 10-K for the most
recent fiscal year and the Company’s other filings with the SEC,
which are available at www.sec.gov.
Investor & Media Contacts:
Rich EisenstadtChief Financial OfficerPhone:
240-654-1450reisenstadt@altimmune.com
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