Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical
company, today announced topline results from its 24-week (12-week
extension) trial of pemvidutide in subjects with NAFLD.
Sixty-six (66) of the 83 subjects who completed
the initial 12-week Phase 1b NAFLD trial consented to participate
in this 12-week extension trial to receive a total of 24 weeks of
treatment, and 64 subjects were enrolled. The trial was conducted
without adjunctive diet and exercise interventions and the
double-blinding of the trial was maintained during the extension
study. The same endpoints as the 12-week parent NAFLD trial were
employed, with a primary efficacy endpoint of percent (%) reduction
in liver fat content; key secondary endpoints were reduction in
liver inflammation, as measured by serum ALT levels and cT1, and
percent weight loss.
The population of the 12-week extension trial
had similar baseline characteristics as the population of the
parent, 12-week Phase 1b NAFLD trial. At baseline, across all
treatment groups, mean BMI was 36.7 kg/m2 and mean liver fat
content (LFC), as measured by MRI-PDFF, was 22.2%. Type 2 diabetes
was present in 26.6% of subjects and 73.4% of study subjects were
of Hispanic ethnicity.
The trial met its primary endpoint in all
pemvidutide treatment groups. At the 1.8 mg and 2.4 mg doses,
subjects receiving pemvidutide achieved mean relative reductions of
liver fat content of 75.2% and 76.4%, respectively; 92.3% and 100%
of subjects, respectively, achieved a 30% reduction in liver fat,
84.6% and 72.7% of subjects, respectively, achieved a 50% reduction
in liver fat, and 53.8% and 45.5% of subjects, respectively,
achieved normalization of liver fat, defined as liver fat fraction
of 5% or less. Statistically significant declines in mean serum ALT
levels were observed in all pemvidutide-treated subjects, and in
subjects with baseline serum ALT ≥30 IU/L, ALT levels declined at
least 17 IU/L at all pemvidutide dose levels. In a subset of
subjects evaluated for cT1 response, 75.0% and 100% of subjects
receiving 1.8 mg or 2.4 mg pemvidutide, respectively, achieved an
80 millisecond (ms) decrease in cT1. Elevated cT1 levels have been
associated with increased risk of major adverse cardiac events
(MACE) and major adverse liver outcomes (MALO), and an 80 ms
reduction has been associated with a 2-point reduction of NAFLD
Activity Score (NAS).
The trial also met its key secondary weight loss
endpoint in all pemvidutide treatment groups. Employing an efficacy
estimand, mean weight losses of 7.2% (placebo-adjusted 6.0%) in
subjects without diabetes and 6.2% (placebo-adjusted 4.8%) in all
subjects were achieved at the 1.8 mg dose.
Pemvidutide was generally well tolerated. A
total of 3 serious or severe adverse events (AEs) were reported,
each unrelated to study drug administration (chest pain
post-elective cardiac stent placement; Salmonella infection; and
hypertension greater than 3 weeks after the completion of
treatment). Three AEs led to treatment discontinuation, 1 being the
Salmonella infection, and 2 gastrointestinal AEs, 1 (6.3%) at the
1.2 mg dose and 1 (6.7%) at the 1.8 mg dose. As expected,
gastrointestinal events comprised the majority of AEs and were
predominantly mild in nature. No clinically significant ALT
elevations were observed. Glycemic control was maintained, with
pemvidutide groups demonstrating trends toward improvements in
fasting glucose and HbA1c over the 24 weeks of treatment.
Meaningful reductions in systolic blood pressure were observed, and
increases in heart rate, typical of the incretin class of agents,
were minimal at 0 to 4 beats per minute and independent of
dose.
“We have seen in recent study announcements that
the magnitudes of change in non-invasive markers like liver fat
reduction and ALT are associated with improvement in non-alcoholic
steatohepatitis (NASH) histopathology. The impressive results
announced today suggest a high likelihood of success on
histopathological assessment in Phase 2b,” said Stephen Harrison,
M.D., Chairman and Co-Founder of Pinnacle Clinical Research and
Summit Clinical Research. “Effective weight loss is also extremely
important for these patients, as many suffer from metabolic
co-morbidities such as obesity, hyperlipidemia and diabetes putting
them at greater risk for cardiovascular disease. I believe
pemvidutide is one of the few candidate drugs for NASH with the
potential to deliver in a meaningful way on both NASH activity and
weight loss and that the magnitude and consistency of these results
place pemvidutide among the most promising agents in development
for NASH.”
“These results, which include some of the most
compelling reductions in liver fat content observed to date,
together with robust reductions in ALT and cT1, highlight the
potential for pemvidutide to achieve significant rates of NASH
resolution and fibrosis improvement in biopsy-driven NASH trials,”
said Vipin K. Garg, Ph.D., President and Chief Executive Officer of
Altimmune. “We believe that both NASH and obesity are important
value drivers of our pemvidutide program. We look forward to the
weight loss data from the interim analysis of our MOMENTUM obesity
trial in Q1 2023 and commencing a Phase 2b NASH trial in 2023.”
Summary of Efficacy
Findings
Endpoint |
Treatment |
|
Placebo |
1.2 mg |
1.8 mg |
2.4 mg |
Primary Endpoint—Liver Fat Content |
n = 18 |
n=14 |
n=13 |
n=11 |
Liver fat reduction, absolute, % change, LSM (SE) |
1.6 (0.8) |
11.2 (2.3) *** |
17.0 (2.4) *** |
15.6 (2.1) *** |
Liver fat reduction, relative, % change, LSM (SE) |
14.0 (3.8) |
56.3 (11.6) *** |
75.2 (8.1) *** |
76.4 (5.9) *** |
Proportion of subjects with 30% reduction, (%) |
5.6 |
76.9 **** |
92.3 **** |
100.0 **** |
Proportion of subjects with 50% reduction, (%) |
0.0 |
61.5 *** |
84.6 **** |
72.7 **** |
Proportion of subjects with normalization, (%) |
0.0 |
30.8 * |
53.8 *** |
45.5 ** |
Secondary Endpoint—Markers of Inflammation |
ALT, change from baseline, IU/L, LSM (SE) |
n = 19 |
n=16 |
n=15 |
n=14 |
-2.2 (2.5) |
-13.3 (3.7) ** |
-13.7 (5.1) ** |
-15.2 (5.8) ** |
ALT, change from baseline, IU/L, LSM (SE), baseline ≥ 30 IU/L |
n = 13 |
n=7 |
n=10 |
n=9 |
-3.1 (3.5) |
-17.0 (7.6) * |
-17.7 (7.2) * |
-20.6 (9.8) * |
Proportion of subjects with cT1 response, (%) |
n = 6 |
n=7 |
n=4 |
n=2 |
0.0 |
85.7 ** |
75.0 * |
100.0 * |
Secondary Endpoint—Weight Loss |
Weight loss, no diabetes, (% change), LSM (SE) |
n = 14 |
n=13 |
n=9 |
n=11 |
1.2 (0.7) |
5.2 (1.7) ** |
7.2 (1.1) *** |
5.8 (1.6) ** |
Weight loss, diabetes, (% change), LSM (SE) † |
n = 5 |
n=3 |
n=6 |
n=3 |
3.4 (2.1) |
4.3 (1.9) |
5.3 (2.7) |
3.5 (2.5) |
Weight loss, all subjects, (% change), LSM (SE) |
n = 19 |
n=16 |
n=15 |
n=14 |
1.4 (0.7) |
5.1 (1.4) ** |
6.2 (1.3) *** |
5.2 (1.4) ** |
Normalization of liver fat defined as ≤ 5%; cT1 response define
as an 80 ms change from baseline; LSM, least square mean† High
variability due to the small numbers of diabetic subjects (n = 5,
3, 6, 3 in respective treatment groups) *p < .05; ** p <
0.01, *** p < 0.001, ****p < 0.0001 compared with
placebo.
Glycemic Control
Characteristic |
Treatment |
Placebo |
1.2 mg |
1.8 mg |
2.4 mg |
Non-diabetes |
n=14 |
n=13 |
n=9 |
n=11 |
Fasting glucose |
Baseline, mg/dL, mean (SD) |
96.2 (12.4) |
99.4 (11.9) |
96.0 (12.4) |
99.3 (13.6) |
Week 24, mg/dL, mean (SD) |
93.3 (12.1) |
99.1 (13.1) |
96.9 (12.5) |
98.4 (24.5) |
HbA1c |
Baseline, %, mean (SD) |
5.8 (0.2) |
5.7 (0.3) |
5.7 (0.2) |
5.5 (0.4) |
Week 24, %, mean (SD) |
5.7 (0.3) |
5.8 (0.3) |
5.8 (0.3) |
5.6 (0.3) |
Diabetes |
n=5 |
n=3 |
n=6 |
n=3 |
Fasting glucose |
Baseline, mg/dL, mean (SD) |
111.5 (19.2) |
132.1 (28.2) |
120.2 (37.1) |
147.4 (40.4) |
Week 24, mg/dL, mean (SD) |
109.4 (14.8) |
123.4 (50.8) |
109.0 (13.1) |
75.5 (29.0) |
HbA1c |
Baseline, %, mean (SD) |
6.1 (0.6) |
7.8 (1.4) |
6.4 (0.5) |
6.8 (1.3) |
Week 24, %, mean (SD) |
6.4 (1.1) |
7.4 (2.3) |
6.4 (0.3) |
6.3 (1.3) |
Summary of Safety Findings
Characteristic |
Treatment |
Placebo(n = 19) |
1.2 mg(n=16) |
1.8 mg(n=15) |
2.4 mg(n=14) |
Serious or severe AEs |
n (%) |
1 (5.3%) |
1 (6.3%) |
1 (6.7%) |
0 (0.0 %) |
AEs leading to treatment discontinuation |
n (%) |
0 (0.0%) |
2 (12.5%) |
1 (6.7%) |
0 (0.0%) |
Nausea |
Mild |
n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
1 (7.1%) |
Moderate |
n (%) |
0 (0.0%) |
0 (0.0%) |
3 (20.0%) |
0 (0.0%) |
Vomiting |
Mild |
n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
Moderate |
n (%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
0 (0.0%) |
Diarrhea |
Mild |
n (%) |
1 (5.3%) |
0 (0.0%) |
1 (6.7%) |
0 (0.0%) |
Moderate |
n (%) |
0 (0.0%) |
1 (6.3%) |
0 (0.0%) |
0 (0.0%) |
Constipation |
Mild |
n (%) |
0 (0.0%) |
0 (0.0%) |
1 (6.7%) |
0 (0.0%) |
Moderate |
n (%) |
1 (5.3%) |
1 (6.3%) |
0 (0.0%) |
0 (0.0%) |
Systolic Blood Pressure, mm Hg, LSM (SE) |
-2.3 (2.8) |
-10.1 (4.2) * |
-5.5 (3.7) |
-12.0 (3.5) * |
Diastolic Blood Pressure, mm Hg, LSM (SE) |
-2.5 (1.5) |
-2.9 (2.6) |
-4.0 (3.7) |
-3.8 (2.8) |
Heart Rate, mmHg, LSM (SE) |
-1.0 (1.7) |
3.7 (1.8) |
0.5 (2.8) |
-0.1 (1.8) |
A total of 3 serious or severe adverse events (AEs) were
reported, each unrelated to study drug administration (chest pain
post-elective cardiac stent placement; Salmonella infection; and
hypertension greater than 3 weeks after the completion of
treatment), with only the Salmonella infection leading to treatment
discontinuation. The other AEs leading to treatment discontinuation
were mild (Grade 1) abdominal pain in 2 subjects. No significant
ALT elevations were reported. *p < .05 compared with
placebo.
About Pemvidutide
Pemvidutide 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. At both 12 and 24 weeks of Phase 1b
clinical trials, NAFLD subjects treated with pemvidutide
demonstrated promising reductions in liver fat content, serum ALT
levels and body weight.
Conference Call
InformationAltimmune management will host a conference
call and webcast with a slide presentation presented by Dr. Stephen
A. Harrison beginning at 8:30 am E.T. 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 Information: |
Date: |
Tuesday,
December 20 |
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 Altimmune
Altimmune 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 (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.
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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 our clinical assets, the timing of the data readouts
of the NAFLD trials, the Phase 2 obesity clinical 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,” “plan,”
“predict” and similar expressions and their variants, as they
relate to Altimmune, Inc. (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 from the ongoing conflict in Ukraine
and the COVID-19 pandemic, 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 liver fat content
and demographics in the Phase 1b NAFLD study on the success of
future trials; the reliability of the results of studies 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, including under the heading “Risk Factors” in
the Company’s annual report on Form 10-K for the fiscal year ended
December 31, 2021 and our 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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