Akero Therapeutics, Inc. (Nasdaq: AKRO), a clinical-stage company
developing transformational treatments for patients with serious
metabolic disease marked by high unmet medical need, today reported
a 36-week analysis of SYMMETRY, a 96-week Phase 2b study evaluating
the efficacy and safety of its lead product candidate efruxifermin
(EFX) in patients with compensated cirrhosis (F4) due to
nonalcoholic steatohepatitis (NASH).
A trend was observed for the primary endpoint of fibrosis
improvement at 36 weeks, with 22% and 24% of the 28mg and 50mg
EFX-treated groups, respectively, experiencing at least a one-stage
improvement in liver fibrosis and no worsening of NASH, compared
with 14% for placebo. In addition, 4% of patients in each of the
EFX-treated groups experienced a three- or two-stage fibrosis
improvement without worsening of NASH – from compensated cirrhosis
(F4) to F1 or F2, compared with 0% for placebo. Statistically
significant rates of NASH resolution in 63% and 60% of patients at
week 36 were observed for the 28mg and 50mg EFX-treated groups,
respectively, compared with 26% for placebo, representing the
highest response rates reported to date for NASH resolution in this
patient population. Statistically significant improvements were
also observed for both EFX groups in non-invasive markers of liver
injury and fibrosis, insulin sensitization and lipoproteins.
“Although no head-to-head comparative studies have been
conducted, and despite the short treatment with EFX, the week 36
SYMMETRY results are the strongest data set reported to date in a
placebo-controlled trial in the difficult-to-treat population of
patients with cirrhosis due to NASH,” said Stephen Harrison, M.D.,
founder and chairman of Pinnacle Clinical Research and Akero’s
SYMMETRY study’s principal investigator. “Patients with cirrhosis
have high levels of hepatic collagen and this takes time to resorb
even though synthesis of collagen was rapidly and substantially
reduced by EFX. I’m encouraged that statistically significant
improvements on multiple measures of NASH pathogenesis were
observed in EFX-treated patients. EFX shows promise for stabilizing
and improving liver health for patients with cirrhosis, and I look
forward to seeing the final SYMMETRY study results.”
Patients with cirrhosis due to NASH face a poor prognosis.
Unless they receive a transplant, only half survive beyond 5 years.
This is due to a greatly depleted population of normally
functioning liver cells leaving the liver with much less capacity
to perform its many functions, vital for patient health. Not only
are the odds of survival poor, but as cirrhosis progresses to
decompensation, and end-stage disease, patient quality of life is
severely compromised. This underlines the high unmet medical need
to at least arrest progression or preferably reverse cirrhosis due
to NASH.
“We believe this analysis of the SYMMETRY study contributes to a
growing body of evidence for EFX’s potential to benefit patients
with NASH who are either cirrhotic or pre-cirrhotic.,” said Andrew
Cheng, M.D., Ph.D., president and chief executive officer of Akero.
“We set a high bar with the primary endpoint after only 36 weeks of
treatment. Viewing these data in their totality, including a
fibrosis improvement trend, reports of regression from cirrhosis to
stage two fibrosis, statistically significant rates of NASH
resolution, and statistically significant and sustained reductions
in markers of liver injury and fibrosis after 36 weeks, we believe
EFX has the potential to show additional improvements for patients
after the long-term follow-up period is complete at Week 96.”
Summary of Week 36 Biopsy
Endpoints1
Measure (Mean) |
Placebo(N=57) |
28mg(N= 46) |
50mg (N= 50) |
Improvement in at least one stage of fibrosis without worsening
NASH (%) |
14 |
22 |
24 |
|
Placebo(N=46) |
28mg(N= 38) |
50mg (N= 42) |
Resolution of NASH (%) |
26 |
63 ** |
60 ** |
NASH resolution AND improvement of at least one stage of fibrosis
(%) |
9 |
21 |
14 |
1 Consensus readSource Data: Liver Biopsy Analysis Set (fibrosis
improvement); Liver Biopsy Analysis Set (definitive NASH only)
(resolution of NASH and combined endpoint)** p<0.01, versus
placebo (Cochran–Mantel–Haenszel test)
Summary of Week 36 Changes in Non-invasive Markers of
Fibrosis and Liver Injury
Measure (LS Mean Change From Baseline to Week
36) |
Placebo(N=58) |
28mg(N= 46-47) |
50mg (N= 50-51) |
Pro-C3 (µg/L) (2nd Generation ELISA) |
-16 |
-59 *** |
-49 *** |
ELF Score |
+0.1 |
-0.2 * |
-0.3 *** |
Liver Stiffness (kPa) (FibroScan) |
-4.3 †† |
-3.6 † |
-3.8 †† |
ALT (U/L) |
-4.9 |
-12.7 ** |
-11.4 ** |
AST (U/L) |
-2.7 |
-10.1 *** |
-11.7 *** |
Source Data: Full Analysis Set* p<0.05, ** p<0.01, ***
p<0.001, versus placebo (Mixed Model Repeated Measures [MMRM])†
p<0.05, †† p<0.01, versus baseline (MMRM)
Summary of Week 36 Changes in Serum Markers of Glucose
and Lipid Metabolism
Measure (LS Mean Change From Baseline to Week
36) |
Placebo(N=58-59) |
28mg(N= 46-47) |
50mg (N= 50) |
HbA1c (%, absolute) |
-0.1 |
-0.4 †† |
-0.2 |
C-Peptide (%) |
-10 |
-22 * |
-26 ** |
Adiponectin (%) |
+9 |
+114 *** |
+92 *** |
Triglycerides (%) |
-5 |
-23 *** |
-29 *** |
Non-HDL Cholesterol (%) |
-3 |
-10 ††† |
-15 ** |
LDL Cholesterol (%) |
-1 |
-5 |
-10 ††† |
HDL Cholesterol (%) |
+1 |
+21 *** |
+24 *** |
Body Weight (kg) |
-0.8 |
-0.8 |
-1.4 † |
Source Data: Full Analysis Set* p<0.05, ** p<0.01, ***
p<0.001, versus placebo (MMRM)† p<0.05, †† p<0.01, †††
p<0.001, versus baseline (MMRM)
EFX was reported to be generally well-tolerated. Across all
three groups, there was one death in a placebo patient who had
pneumonia. Twenty-one serious adverse events were reported, which
were generally balanced across dose groups. None of these were
reported as treatment-related by the clinical investigators. A
total of 12 patients were discontinued due to adverse events
determined by the investigator to be drug-related, one in the
placebo group, three in the 28mg group and eight in the 50mg group.
The majority of these discontinuations were due to grade 1-2
diarrhea, which accounted for five patients due to diarrhea in the
50mg group. Overall, the most frequent adverse events were
transient, mild-to-moderate gastro-intestinal grade 1 or 2
events.
Conference Call / Webcast DetailsThe company
will host a conference call and webcast with slide presentation at
8:00 a.m. ET. Please click here
to register for the event. The live webcast will
be available on the Events & Presentations page of the Akero
website, with the recording and presentation available following
the event.
About NASHNASH is a serious form of
non-alcoholic fatty liver disease (NAFLD) that is estimated to
affect 17 million Americans. NASH is characterized by an excessive
accumulation of fat in the liver that causes stress and injury to
liver cells, leading to inflammation and fibrosis, which can
progress to cirrhosis, liver failure, cancer and eventually death.
Approximately 20% of patients with NASH will progress to cirrhosis,
which has a higher risk of mortality. There are no approved
treatments for the condition and NASH is the fastest growing cause
of liver transplants and liver cancer in the US and Europe.
About SYMMETRY The Phase 2b SYMMETRY main study
is a multicenter, randomized, double-blind, placebo-controlled,
clinical trial in biopsy-confirmed NASH patients with compensated
cirrhosis (F4, Child-Pugh class A). One hundred eighty-two patients
have been randomized to receive once-weekly subcutaneous dosing of
28mg EFX, 50mg EFX, or placebo. The primary endpoint for the trial
was the proportion of subjects who achieve ≥ 1 stage improvement in
fibrosis with no worsening of NASH at week 36. Secondary endpoints
include the proportion of patients who achieve NASH resolution with
no worsening of fibrosis, the proportion of patients who achieve ≥
1 stage improvement in fibrosis and NASH resolution, change from
baseline to week 36 in non-invasive markers of liver injury and
fibrosis, glycemic control, lipoproteins, and body weight, as well
as evaluation of safety and tolerability. Patients are continuing
to receive EFX or placebo for up to 96 weeks.
About EfruxiferminEfruxifermin is Akero’s lead
product candidate for NASH, currently being evaluated in the
ongoing Phase 2b HARMONY and SYMMETRY studies. EFX is designed to
reduce liver fat and inflammation, reverse fibrosis, increase
insulin sensitivity and improve lipids. This holistic approach
offers the potential to address the complex, multi-system disease
state of NASH, including improvements in lipoprotein risk factors
linked to cardiovascular disease – the leading cause of death in
NASH patients. Engineered to mimic the biological activity profile
of native FGF21, EFX is designed to offer convenient once-weekly
dosing and has been generally well-tolerated in clinical trials to
date.
About Akero TherapeuticsAkero Therapeutics
is a clinical-stage company developing transformational treatments
for patients with serious metabolic diseases marked by high unmet
medical need, including NASH, a disease without any approved
therapies. Akero's lead product candidate, EFX, is a differentiated
Fc-FGF21 fusion protein that has been engineered to mimic the
balanced biological activity profile of native FGF21, an endogenous
hormone that alleviates cellular stress and regulates metabolism
throughout the body. EFX is designed to offer convenient
once-weekly subcutaneous dosing. EFX is currently being evaluated
in two Phase 2b clinical trials: the HARMONY study in patients with
pre-cirrhotic NASH (F2-F3 fibrosis), and the SYMMETRY study in
patients with cirrhotic NASH (F4 fibrosis, compensated). Akero is
headquartered in South San Francisco. Visit us at akerotx.com
and follow us on LinkedIn and Twitter for more
information.
Forward Looking Statements Statements contained
in this press release regarding matters that are not historical
facts are "forward-looking statements'' within the meaning of the
Private Securities Litigation Reform Act of 1995. Because such
statements are subject to risks and uncertainties, actual results
may differ materially from those expressed or implied by such
forward-looking statements, including, but not limited to,
statements regarding Akero’s business plans and objectives,
including future plans or expectations for EFX, the therapeutic
effects of EFX, as well as the dosing, safety and tolerability of
EFX; the timing and completion of enrollment of Akero’s Phase 3
SYNCHRONY program by end of this year; and upcoming milestones,
including the results, and expected timing to report the long-term
follow-up week 96 results of Akero’s Phase 2b SYMMETRY study. Any
forward-looking statements in this press release are based on
management's current expectations of future events and are subject
to a number of risks and uncertainties that could cause actual
results to differ materially and adversely from those set forth in
or implied by such forward-looking statements. Risks that
contribute to the uncertain nature of the forward-looking
statements include: the success, cost, and timing of Akero’s
product candidate development activities and planned clinical
trials; Akero’s ability to execute on its strategy; positive
results from any of its clinical studies may not necessarily be
predictive of the results of future or ongoing clinical studies;
regulatory developments in the United States and foreign countries;
Akero’s ability to fund operations; as well as those risks and
uncertainties set forth more fully under the caption "Risk
Factors'' in Akero’s most recent Annual Report on Form 10-K and
Quarterly Report on Form 10-Q, as filed with the Securities and
Exchange Commission (SEC) as well as discussions of potential
risks, uncertainties and other important factors in Akero’s other
filings and reports with the SEC. All forward-looking statements
contained in this press release speak only as of the date on which
they were made. Akero undertakes no obligation to update such
statements to reflect events that occur or circumstances that exist
after the date on which they were made.
Investor Contact:Austin
Murtagh212.698.8696IR@akerotx.com
Media Contact:Sarah
O’Connell732.456.0092soconnell@vergescientific.com
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