ACHAOGEN, INC. (NASDAQ:AKAO) Files An 8-K Other Events
Item 8.01 Other Events.
On December 12, 2016, Achaogen, Inc. (Achaogen) announced that
its lead product candidate, plazomicin, met the objective of
non-inferiority compared to meropenem for the U.S. Food and Drug
Administration (FDA) and achieved superiority for the European
Medicines Agency (EMA) primary efficacy endpoints in the Phase 3
EPIC registration trial in patients with complicated urinary
tract infections (cUTI) and acute pyelonephritis (AP). In
addition, in the Phase 3 CARE trial in patients with serious
infections due to carbapenem-resistant Enterobacteriaceae (CRE),
a lower rate of mortality or serious disease-related
complications was observed for plazomicin compared with colistin
therapy, one of the few remaining antibiotics for treatment of
infections due to CRE.
its lead product candidate, plazomicin, met the objective of
non-inferiority compared to meropenem for the U.S. Food and Drug
Administration (FDA) and achieved superiority for the European
Medicines Agency (EMA) primary efficacy endpoints in the Phase 3
EPIC registration trial in patients with complicated urinary
tract infections (cUTI) and acute pyelonephritis (AP). In
addition, in the Phase 3 CARE trial in patients with serious
infections due to carbapenem-resistant Enterobacteriaceae (CRE),
a lower rate of mortality or serious disease-related
complications was observed for plazomicin compared with colistin
therapy, one of the few remaining antibiotics for treatment of
infections due to CRE.
Achaogen plans to submit a New Drug Application (NDA), which will
include EPIC and CARE data, to the FDA in the second half of
2017. Achaogen also plans to submit a Marketing Authorization
Application (MAA) to the EMA in 2018. In addition, Achaogen plans
to publicly present detailed results from both the EPIC and CARE
trials in 2017.
include EPIC and CARE data, to the FDA in the second half of
2017. Achaogen also plans to submit a Marketing Authorization
Application (MAA) to the EMA in 2018. In addition, Achaogen plans
to publicly present detailed results from both the EPIC and CARE
trials in 2017.
In the EPIC trial, plazomicin successfully met the objective of
non-inferiority compared to meropenem for the FDA-specified
primary efficacy endpoints, and achieved superiority for the
EMA-specified primary efficacy endpoints.
non-inferiority compared to meropenem for the FDA-specified
primary efficacy endpoints, and achieved superiority for the
EMA-specified primary efficacy endpoints.
Results for FDA pre-specified composite endpoint of clinical cure
and microbiological eradication in the microbiological modified
intent-to-treat (mMITT) population were as follows:
and microbiological eradication in the microbiological modified
intent-to-treat (mMITT) population were as follows:
|
Day 5: 88.0% plazomicin vs. 91.4% meropenem (difference
-3.4%, 95% CI: -10.0, 3.1%), indicating statistical non-inferiority |
|
Test-of-Cure: 81.7% plazomicin vs. 70.1% meropenem
(difference 11.6%, 95% CI: 2.7, 20.3%), indicating statistical superiority |
Results for EMA-specified endpoints of microbiological
eradication at the test-of-cure visit were as follows:
eradication at the test-of-cure visit were as follows:
|
mMITT: 87.4% plazomicin vs. 72.1% meropenem (difference
15.4%, 95% CI: 7.5, 23.2%), indicating statistical superiority |
|
ME: 90.5% plazomicin vs. 76.6% meropenem (difference 13.9%,
95% CI: 6.3, 21.7%), indicating statistical superiority |
Phase 3 EPIC Trial in Patients with cUTI: Summary of FDA and EMA
Primary Efficacy Endpoints
Primary Efficacy Endpoints
(* indicates statistical superiority)
|
Plazomicin
n/N (%)
|
Meropenem
n/N (%)
|
Difference (%)a (95% CI)
|
|
|
Composite endpoint at Day 5, mMITT (FDA)
|
168/191 (88.0%)
|
180/197 (91.4%)
|
-3.4% (-10.0, 3.1%)
|
|
Composite endpoint at TOC, mMITT (FDA)
|
156/191 (81.7%)
|
138/197 (70.1%)
|
11.6% (2.7, 20.3%)*
|
|
Microbiological eradication at TOC, mMITT (EMA)
|
167/191 (87.4%)
|
142/197 (72.1%)
|
15.4% (7.5, 23.2%)*
|
|
Microbiological eradication at TOC, ME (EMA)
|
162/179 (90.5%)
|
134/175 (76.6%)
|
13.9% (6.3, 21.7%)*
|
CI: confidence interval; ME: microbiologically evaluable; mMITT:
microbiological modified intent-to-treat; TOC: test-of-cure;
a Difference = plazomicin minus meropenem
microbiological modified intent-to-treat; TOC: test-of-cure;
a Difference = plazomicin minus meropenem
Plazomicin was well tolerated with no new safety concerns
identified in the EPIC trial. Total treatment emergent adverse
events (TEAEs) related to renal function were reported in 3.6%
and 1.3% of patients in the plazomicin and meropenem groups,
respectively. TEAEs related to cochlear or vestibular function
were reported in a single patient in each of the plazomicin and
meropenem treatment groups. Both events were considered mild and
resolved completely.
identified in the EPIC trial. Total treatment emergent adverse
events (TEAEs) related to renal function were reported in 3.6%
and 1.3% of patients in the plazomicin and meropenem groups,
respectively. TEAEs related to cochlear or vestibular function
were reported in a single patient in each of the plazomicin and
meropenem treatment groups. Both events were considered mild and
resolved completely.
In the Phase 3 CARE trial in patients with serious infections due
to CRE a lower rate of mortality or serious disease-related
complications was observed for plazomicin compared with colistin
therapy.
to CRE a lower rate of mortality or serious disease-related
complications was observed for plazomicin compared with colistin
therapy.
Results from the CARE trial were as follows:
|
Day 28 all-cause mortality or significant disease related
complications (primary endpoint); 23.5% plazomicin vs. 50.0% colistin (difference 26.5%, 90% CI: -0.7, 51.2%) |
|
Day 28 all-cause mortality; 11.8% plazomicin vs. 40.0%
colistin (difference 28.2%, 90% CI: 0.7, 52.5%) |
Phase 3 CARE Trial in Patients with BSI or HABP/VABP due to CRE
(Cohort 1 mMITT population)
|
Plazomicin
n/N (%)
|
Colistin
n/N (%)
|
Differencea (90% CI)
|
Relative Reduction
|
|
|
Day 28 all-cause mortality or significant
disease-related complications |
4/17 (23.5%)
|
10/20 (50.0%)
|
26.5%
(-0.7, 51.2%)
|
53.0%
|
|
Day 28 all-cause mortality
|
2/17 (11.8%)
|
8/20 (40.0%)
|
28.2%
(0.7, 52.5%)
|
70.5%
|
a Difference = colistin minus plazomicin
The safety profile of plazomicin was favorable to that of
colistin in critically ill patients in the CARE trial. Study
drug-related TEAEs related to renal function were reported in
16.7% and 38.1% of patients in the plazomicin and colistin
groups, respectively. No TEAEs related to cochlear or vestibular
function were reported in either group.
colistin in critically ill patients in the CARE trial. Study
drug-related TEAEs related to renal function were reported in
16.7% and 38.1% of patients in the plazomicin and colistin
groups, respectively. No TEAEs related to cochlear or vestibular
function were reported in either group.
About the EPIC Trial> EPIC (Evaluating plazomicin in cUTI) was
a multinational, randomized, controlled, double-blind clinical
trial in adult patients with cUTI and AP. The trial enrolled 609
patients who were randomized 1:1 to receive plazomicin 15 mg/kg
as a once daily 30-minute intravenous (IV) infusion or meropenem
1.0 gram every 8 hours as a 30 minute IV infusion. After a
minimum of 4 days of IV therapy, patients who met
protocol-defined criteria for improvement were allowed to
step-down to oral levofloxacin to complete a total of 7 to 10
days of therapy (IV plus oral).
a multinational, randomized, controlled, double-blind clinical
trial in adult patients with cUTI and AP. The trial enrolled 609
patients who were randomized 1:1 to receive plazomicin 15 mg/kg
as a once daily 30-minute intravenous (IV) infusion or meropenem
1.0 gram every 8 hours as a 30 minute IV infusion. After a
minimum of 4 days of IV therapy, patients who met
protocol-defined criteria for improvement were allowed to
step-down to oral levofloxacin to complete a total of 7 to 10
days of therapy (IV plus oral).
About the CARE Trial
CARE (Combating Antibiotic Resistant Enterobacteriaceae) was a
multinational, open label, Phase 3 clinical trial evaluating the
efficacy and safety of plazomicin in patients with serious
bacterial infections due to CRE. The study included two cohorts
of patients. Cohort 1 (N=39) was a randomized,
comparator-controlled cohort to compare plazomicin with colistin
(either in combination with meropenem or tigecycline) for the
treatment of bloodstream infection (BSI), hospital acquired
bacterial pneumonia (HABP) or ventilator associated bacterial
pneumonia (VABP) due to CRE. Cohort 1 enrolled 30 patients with
BSI and 9 patients with HABP/VABP. Cohort 2 (N=30) was a
single-arm expanded access cohort to evaluate plazomicin-based
therapy in patients with BSI, HABP/VABP or cUTI due to CRE who
were not eligible for enrollment in Cohort 1.
multinational, open label, Phase 3 clinical trial evaluating the
efficacy and safety of plazomicin in patients with serious
bacterial infections due to CRE. The study included two cohorts
of patients. Cohort 1 (N=39) was a randomized,
comparator-controlled cohort to compare plazomicin with colistin
(either in combination with meropenem or tigecycline) for the
treatment of bloodstream infection (BSI), hospital acquired
bacterial pneumonia (HABP) or ventilator associated bacterial
pneumonia (VABP) due to CRE. Cohort 1 enrolled 30 patients with
BSI and 9 patients with HABP/VABP. Cohort 2 (N=30) was a
single-arm expanded access cohort to evaluate plazomicin-based
therapy in patients with BSI, HABP/VABP or cUTI due to CRE who
were not eligible for enrollment in Cohort 1.
The primary analysis for Cohort 1 was conducted in the mMITT
population (patients with confirmed CRE infection) and was
defined as all-cause mortality at Day 28 or significant disease
related complications. Due to limitations of the small sample
size, no formal statistical hypothesis testing was performed, but
a two-sided 90% exact confidence interval is provided to describe
the degree of variability around the observed differences.
population (patients with confirmed CRE infection) and was
defined as all-cause mortality at Day 28 or significant disease
related complications. Due to limitations of the small sample
size, no formal statistical hypothesis testing was performed, but
a two-sided 90% exact confidence interval is provided to describe
the degree of variability around the observed differences.
Forward-Looking Statements
All statements other than statements of historical facts
contained herein are forward-looking statements reflecting the
current beliefs and expectations of management made to the safe
harbor provisions of the Private Securities Litigation Reform Act
of 1995, including, but not limited to, Achaogens plan to submit
an NDA to the FDA in the second half of 2017, Achaogens plans to
submit an MAA to the EMA in 2018, Achaogens expectations
regarding whether the full CARE trial results will be submitted
as supportive data with the plazomicin NDA submission and
Achaogens plan to publicly present detailed results from both the
EPIC and CARE trials in 2017. Such forward-looking statements
involve known and unknown risks, uncertainties and other
important factors that may cause Achaogens actual results,
performance or achievements to be materially different from any
future results, performance or achievements expressed or implied
by the forward-looking statements. Such risks and uncertainties
include, among others, the uncertainties inherent in the
contained herein are forward-looking statements reflecting the
current beliefs and expectations of management made to the safe
harbor provisions of the Private Securities Litigation Reform Act
of 1995, including, but not limited to, Achaogens plan to submit
an NDA to the FDA in the second half of 2017, Achaogens plans to
submit an MAA to the EMA in 2018, Achaogens expectations
regarding whether the full CARE trial results will be submitted
as supportive data with the plazomicin NDA submission and
Achaogens plan to publicly present detailed results from both the
EPIC and CARE trials in 2017. Such forward-looking statements
involve known and unknown risks, uncertainties and other
important factors that may cause Achaogens actual results,
performance or achievements to be materially different from any
future results, performance or achievements expressed or implied
by the forward-looking statements. Such risks and uncertainties
include, among others, the uncertainties inherent in the
preclinical and clinical development process; the risk of failure
to successfully validate, develop and obtain regulatory clearance
or approval for an in vitro diagnostic (IVD) assay for
plazomicin; the risks and uncertainties of the regulatory
approval process; the risks and uncertainties of
commercialization and gaining market acceptance; the risk that
bacteria may evolve resistance to plazomicin; risks and
uncertainties as to Achaogens ability to raise additional capital
to support the development and potential commercialization of
plazomicin and its other programs; uncertainties regarding the
availability of adequate third-party coverage and reimbursement
for newly approved products; Achaogens reliance on third parties
to conduct certain preclinical studies and all of its clinical
trials; Achaogens reliance on third-party contract manufacturing
organizations to manufacture and supply its product candidates
and certain raw materials used in the production thereof;
Achaogens dependence on its President and Chief Executive
Officer; risks and uncertainties related to the acceptance of
government funding for certain of Achaogens programs, including
the risk that the Biomedical Advanced Research and Development
Authority (BARDA) could terminate Achaogens contract for the
funding of the plazomicin development program; risk of third
party claims alleging infringement of patents and proprietary
rights or seeking to invalidate Achaogens patents or proprietary
rights; and the risk that Achaogens proprietary rights may be
insufficient to protect its technologies and product candidates.
For a further description of the risks and uncertainties that
could cause actual results to differ from those expressed in
these forward-looking statements, as well as risks relating to
Achaogens business in general, see Achaogens current and future
reports filed with the Securities and Exchange Commission,
including its Quarterly Report on Form 10-Q for the fiscal
quarter ended September 30, 2016 , and its Annual Report on Form
10-K for the fiscal year ended December 31, 2015. Achaogen does
not plan to publicly update or revise any forward-looking.
to successfully validate, develop and obtain regulatory clearance
or approval for an in vitro diagnostic (IVD) assay for
plazomicin; the risks and uncertainties of the regulatory
approval process; the risks and uncertainties of
commercialization and gaining market acceptance; the risk that
bacteria may evolve resistance to plazomicin; risks and
uncertainties as to Achaogens ability to raise additional capital
to support the development and potential commercialization of
plazomicin and its other programs; uncertainties regarding the
availability of adequate third-party coverage and reimbursement
for newly approved products; Achaogens reliance on third parties
to conduct certain preclinical studies and all of its clinical
trials; Achaogens reliance on third-party contract manufacturing
organizations to manufacture and supply its product candidates
and certain raw materials used in the production thereof;
Achaogens dependence on its President and Chief Executive
Officer; risks and uncertainties related to the acceptance of
government funding for certain of Achaogens programs, including
the risk that the Biomedical Advanced Research and Development
Authority (BARDA) could terminate Achaogens contract for the
funding of the plazomicin development program; risk of third
party claims alleging infringement of patents and proprietary
rights or seeking to invalidate Achaogens patents or proprietary
rights; and the risk that Achaogens proprietary rights may be
insufficient to protect its technologies and product candidates.
For a further description of the risks and uncertainties that
could cause actual results to differ from those expressed in
these forward-looking statements, as well as risks relating to
Achaogens business in general, see Achaogens current and future
reports filed with the Securities and Exchange Commission,
including its Quarterly Report on Form 10-Q for the fiscal
quarter ended September 30, 2016 , and its Annual Report on Form
10-K for the fiscal year ended December 31, 2015. Achaogen does
not plan to publicly update or revise any forward-looking.
About ACHAOGEN, INC. (NASDAQ:AKAO)
Achaogen, Inc. is a clinical-stage biopharmaceutical company. The Company is engaged in the discovery, development and commercialization of antibacterials to treat multi-drug resistant (MDR) gram-negative infections. The Company is developing plazomicin, its lead product candidate, for the treatment of serious bacterial infections due to MDR Enterobacteriaceae, including carbapenem-resistant enterobacteriaceae (CRE). Plazomicin is an aminoglycoside designed to overcome clinically relevant aminoglycoside resistance mechanisms. In addition, its research and development pipeline includes two programs that specifically target Pseudomonas aeruginosa or Acinetobacter baumannii infections: a program to discover and develop small molecule inhibitors of LpxC, which is an enzyme essential for the synthesis of the outer membrane of gram-negative bacteria, and a therapeutic antibody program. Its development plan for plazomicin includes over two Phase III clinical trials. ACHAOGEN, INC. (NASDAQ:AKAO) Recent Trading Information
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