Primary objective of the trial met with
statistically significant dose response with up to 43.6% relative
reduction (2.1 day improvement) in median time to solid food
tolerance versus placebo in hyper-inflamed patients
Statistically significant dose response with
up to 61.7% reduction in severe organ failure in all patients
versus placebo
Up to 100% reduction in hospital stays longer
than 21 days
Planning End-of-Phase 2 meeting with the FDA
in preparation for a pivotal trial
Conference call to discuss the CARPO topline
results scheduled for 8:30 a.m. ET
today
LA
JOLLA, Calif., June 27,
2024 /PRNewswire/ -- CalciMedica Inc. ("CalciMedica")
(Nasdaq: CALC), a clinical-stage biopharmaceutical company focused
on developing novel calcium release-activated calcium (CRAC)
channel inhibition therapies for acute and chronic inflammatory and
immunologic illnesses, today announced positive topline data from
CARPO, the Company's randomized, double-blind, placebo-controlled
Phase 2b trial evaluating Auxora™ for
the treatment of acute pancreatitis (AP) with accompanying systemic
inflammatory response syndrome (SIRS). The trial established a dose
response for Auxora across multiple endpoints, identified both the
target patient population and the likely drug dose for a pivotal
trial, and re-affirmed Auxora's safety profile and tolerability as
seen in prior clinical trials.
"With these results, CARPO has added significantly to the body
of evidence showing Auxora's potential as an effective treatment
for critically ill patients with acute inflammatory disease and
warrants advancing our drug in both AP and acute kidney injury,"
said Rachel Leheny, Ph.D., Chief
Executive Officer of CalciMedica. "We plan to move quickly towards
initiating our Phase 3 trial in AP and are eager to engage with the
FDA to discuss our trial plans once we have all the data from
CARPO. We look forward to unlocking Auxora's potential to treat
these patients who have few treatment options."
"There are currently no drugs for the treatment of AP and the
CARPO data show a benefit in multiple endpoints, supporting the
need for Auxora," said Joseph
Miller, M.D., Clinical Associate Professor of Emergency
Medicine at Henry Ford Health and Michigan
State University and Associate Director Emergency Care
Research at Henry Ford Health and a principal investigator in the
CARPO trial. "AP is one of the costliest gastrointestinal diseases
for hospitals due to prolonged lengths of stay for severe patients.
By reducing the occurrence of severe organ failure and extended
hospital stays, Auxora may provide significant benefits to patients
with AP and to the health care system and should be welcomed by
clinicians and hospitals."
The CARPO Trial Topline Results:
The Phase 2b CARPO trial was an
international, randomized, double-blind, placebo-controlled,
dose-ranging trial intended to establish Auxora's dose-response and
efficacy in AP with accompanying SIRS. The trial reached its target
enrollment of 216. Patients were randomized into four groups to
receive either high 2.0 mg/kg dose (n=53), medium 1.0 mg/kg dose
(n=56) or low 0.5 mg/kg dose (n=52) of Auxora or a matched dose of
placebo (n=53) intravenously every 24 hours for a total of three
doses. Treatment and observation of patients continued for 30 days.
Patients were stratified by baseline hematocrit, a biomarker
for inflammation severity, so that efficacy in a pre-specified
hyper-inflamed sub-group of patients could be evaluated. These
patients represented approximately 43% of the patients enrolled
(2.0 mg/kg, n=23; 1.0 mg/kg, n=25; 0.5 mg/kg, n=24; and placebo,
n=20). Patients were well-matched for all baseline characteristics
with the exception that the placebo group had approximately 12%
lower proportion of hyper-inflamed patients than the study
overall.
Summary of Efficacy Data:
CARPO met its study objective by showing a dose response for
time to solid food tolerance as well as other clinical endpoints.
The primary endpoint of median time to solid food tolerance in the
pre-specified subgroup of patients with hyper-inflammatory acute
pancreatitis showed a statistically significant dose response with
placebo patients requiring 4.7 days to tolerate solid food and
patients in the high dose group showing a 1.9 day improvement
(41.0% relative risk reduction) when compared to placebo, the
medium dose group a 2.1 day improvement (43.6% relative risk
reduction) and the low dose group a 1.5 day improvement (31.0%
relative risk reduction). In patients without hyper-inflammatory
AP, Auxora did not show a measurable benefit due to the patients
tolerating solid food relatively quickly in all treatment
groups.
Additionally, Auxora demonstrated a statistically significant
dose response in reduction of severe organ failure which was
defined as respiratory failure requiring invasive mechanical
ventilation or 48 hours or more of high-flow nasal canula therapy,
renal failure requiring renal replacement therapy, or
cardiovascular failure requiring the use of vasopressor or
inotropic support for greater than 48 hours. Severe organ failure
occurred in 3.8% of high dose patients, 3.6% of medium dose
patients, 9.6% of low dose patients, and 9.4% of placebo patients,
representing a 59.6% relative risk reduction for the high dose
patients when compared to placebo and 61.7% risk reduction for the
medium dose patients when compared to placebo.
The median length of hospital stay was 5.0 days for the placebo
group while the high dose group showed a reduction in the length of
stay of 1.0 day. The mean length of stay showed a greater benefit:
the placebo patients had a mean stay of 7.1 days and both the high
dose and medium dose patients had a reduction of 1.2 days. In the
patients with hyperinflammatory acute pancreatitis, the reduction
was even greater, 1.5 days for the hyper-inflamed high dose
patients and 1.9 days for the hyper-inflamed medium dose
patients.
The proportion of patients who remained in the hospital for
longer than 21 days was 0% for high dose patients, 1.8% for medium
dose patients, 5.8% for low dose patients, and 5.7% for placebo
patients. Comparing the combined placebo and low dose patients to
the combined high and medium dose patients, this represents a 84.3%
relative risk for a prolonged hospital stay.
Summary of Safety Data:
Auxora was well-tolerated with 20 treatment-emergent serious
adverse events (TESAEs) reported in the placebo group, 14 in the
high dose group, 21 in the medium dose group, and 23 in the low
dose group. None of the TESAEs in the high and medium dose groups
and only 1 in the low dose group were deemed to be drug-related.
There were no related TESAEs in the placebo group.
Treatment-emergent adverse events (TEAEs) led to drug
discontinuation in 3 patients in the placebo group, 2 in the high
dose group, 2 in the medium dose group, and 2 in the low dose
group. TEAEs led to death in 1 patient in the placebo group and 1
in the medium dose group. There were no deaths in the high dose or
low dose group.
"Consistent with our prior Phase 2b CARDEA trial in severe and critical COVID
pneumonia patients and with our Phase 2a trial in AP patients with
SIRS and hypoxemia, CARPO has demonstrated Auxora's potential to
treat some of the more severely ill patients with acute
inflammatory diseases," said Sudarshan
Hebbar, M.D., Chief Medical Officer of CalciMedica.
"Importantly, we found that Auxora provided patients with
clinically meaningful improvements in key outcome measures, while
also being well-tolerated. We have identified the target population
of patients most likely to benefit from Auxora and determined the
likely dose for a pivotal trial. With this information we are more
confident in proceeding with a pivotal program in AP. I want to
thank the patients who enrolled in the trial as well as the
investigators and their study teams for their hard work and
contributions to the success of this trial. CARPO has advanced our
understanding of AP and brought us closer to a solution for this
potentially life-threatening condition for which currently no
approved therapy exists."
"CARPO has demonstrated that patients with hyper-inflammation
benefit most from Auxora. This is encouraging as we initiate
KOURAGE where we have established enrollment criteria that select
the acute kidney injury patients who are most likely to be
suffering from severe inflammation and where reduction of organ
failure is a key metric of efficacy," said Lakhmir Chawla, M.D., Clinical Professor of
Medicine at University of California San
Diego, Chief Medical Officer at ExThera Medical, Scientific
Advisor to CalciMedica, and Chair of the KOURAGE Steering
Committee.
CalciMedica intends to present additional data from CARPO,
including results from the analysis of CTs taken at baseline and
30-days post enrollment, at a medical meeting later this year.
Conference Call and Webcast Details
Stockholders and other interested parties may participate in the
call by following the instructions below. A live webcast of the
event can also be accessed in the "Upcoming Events" section of
CalciMedica's IR website at https://ir.calcimedica.com/. A replay
of the webcast will be available following the completion of the
event.
Participant Webcast Link:
https://app.webinar.net/jDbvg4E9yPn
Participant Dial-in Numbers: 1-800-836-8184 (US) and
1-646-357-8785 (international)
About Auxora™
CalciMedica's lead clinical compound,
Auxora™, is a potent and selective small molecule inhibitor of
Orai1-containing CRAC channels that is being developed for use in
patients with acute inflammatory and immunologic illnesses. CRAC
channels are found on many cell types, including immune system
cells, endothelium cells and pancreatic acinar cells, where
aberrant activation of these channels may play a key role in the
pathobiology of acute and chronic inflammatory syndromes. Auxora is
currently being evaluated in: (i) a Phase 2b trial for acute pancreatitis (AP) with
accompanying systemic inflammatory response syndrome (SIRS), called
CARPO, (ii) a Phase 2 trial in acute kidney injury (AKI) with
associated acute hypoxemic respiratory failure (AHRF), called
KOURAGE, and (iii) an investigator-sponsored Phase 1/2 trial,
called CRSPA, being conducted in pediatric patients with
asparaginase-induced pancreatic toxicity (AIPT) as a side effect of
pediatric acute lymphoblastic leukemia treatment with asparaginase.
There are currently no approved therapies to treat either AP, AKI
or AIPT. In previous trials, patients responded well to Auxora
regardless of severity or cause of disease. CalciMedica is also
exploring the potential of Auxora treatment for other acute
indications including acute respiratory distress
syndrome.
About AP
AP, or inflammation of the pancreas, can be a
life-threatening condition. Moderate or severe AP sometimes leads
to pancreatic cell death or necrosis, systemic inflammation, organ
failure and death. There are an estimated 275,000 hospitalizations
for AP annually in the United
States, of which approximately 40% present with SIRS, a
predictor of moderate and severe disease which can compromise the
function of other tissues or organs, especially the lungs. Organ
failure is responsible for much of the mortality seen in AP. There
is currently no approved therapy for AP. Details of the CARPO trial
are available on clinicaltrials.gov (NCT04681066).
About KOURAGE and AKI
KOURAGE is a randomized,
double-blind, placebo-controlled study that will evaluate 150
patients with Stage 2 and 3 AKI who have AHRF and are receiving
oxygen by non-invasive mechanical ventilation, high flow nasal
cannula or intermittent mandatory ventilation (IMV). AKI denotes a
sudden reduction in kidney function, the organ's ability to clean
and filter the blood. AKI can result as a complication of other
serious illnesses such as sepsis, respiratory infections and
failure, acute pancreatitis, trauma, surgery and burns. There are
approximately 3.7 million patients hospitalized with AKI
in the United States each year with approximately 1.1
million advancing to Stage 2 and Stage 3 AKI, over half of whom
have associated AHRF. The risk of serious morbidities and mortality
is significant for advanced Stage 2 and Stage 3 AKI patients. There
are currently no approved therapies for AKI.
About CalciMedica
CalciMedica is a clinical-stage
biopharmaceutical company focused on developing novel CRAC
channel inhibition therapies for inflammatory and immunologic
diseases. CalciMedica's proprietary technology targets the
inhibition of CRAC channels to modulate the immune response and
protect against tissue cell injury, with the potential to provide
therapeutic benefits in life-threatening inflammatory and
immunologic diseases for which there are currently no approved
therapies. CalciMedica's lead product candidate Auxora™, has
demonstrated positive and consistent clinical results in multiple
completed efficacy clinical trials. CalciMedica has completed a
Phase 2b trial (called CARPO –
NCT04681066) in AP with SIRS and a Phase 2b trial (called CARDEA – NCT04345614) in
COVID pneumonia patients, continues to support the ongoing Phase
1/2 AIPT study (called CRSPA – NCT04195347), with data expected in
2025, and has initiated its Phase 2 study (called KOURAGE –
NCT06374797) in AKI with associated AHRF with data expected in
2025. CalciMedica was founded by scientists from Torrey Pines
Therapeutics and the Harvard CBR Institute for Biomedical Research,
and is headquartered in La Jolla,
CA. For more information, please visit
www.calcimedica.com.
Forward-Looking Statements
This communication contains
forward-looking statements which include, but are not limited to,
statements related to: CalciMedica's business strategy; the
potential benefits of Auxora for treatment of AP patients and the
healthcare system; the dose response for Auxora across multiple
endpoints, the target patient population and the likely drug dose
for a pivotal trial; CalciMedica's planned and ongoing clinical
trials and the timing, design, expected patient enrollment thereof
and the expected timing for the release of data from those trials,
including its plans to present additional data from the Phase
2b CARPO trial of Auxora for AP with
accompanying SIRS at future medical meeting later this year; plans
to move forward rapidly with a pivotal trial of Auxora for AP;
plans regarding its ongoing Phase 1/2 CRSPA trial of Auxora in
pediatric patients with AIPT and its planned Phase 2 KOURAGE trial
of Auxora in AKI with associated AHRF; the potential benefits of
Auxora for the treatment of AIPT and AKI; and the potential of
CalciMedica's proprietary technology to provide therapeutic
benefits in life-threatening inflammatory and immunologic diseases.
These forward-looking statements are subject to the safe harbor
provisions under the Private Securities Litigation Reform Act of
1995. CalciMedica's expectations and beliefs regarding these
matters may not materialize. Actual outcomes and results may differ
materially from those contemplated by these forward-looking
statements as a result of uncertainties, risks, and changes in
circumstances, including, but not limited to, risks and
uncertainties related to: the impact of fluctuations in global
financial markets on CalciMedica's business and the actions it may
take in response thereto; CalciMedica's ability to execute its
plans and strategies; the ability to obtain and maintain regulatory
approval for Auxora; results from clinical trials or preclinical
studies may not be indicative of results that may be observed in
the future; potential safety and other complications from Auxora;
the scope, progress and expansion of developing and commercializing
Auxora; the size and growth of the market therefor and the rate and
degree of market acceptance thereof; economic, business,
competitive, and/or regulatory factors affecting the business of
CalciMedica generally; CalciMedica's ability to protect its
intellectual property position; and the impact of government laws
and regulations. Additional risks and uncertainties that could
cause actual outcomes and results to differ materially from those
contemplated by the forward-looking statements are included under
the caption "Risk Factors" in CalciMedica's Quarterly Report on
Form 10-Q for the quarter ended March 31,
2024, and elsewhere in CalciMedica's subsequent reports on
Form 10-K, Form 10-Q or Form 8-K filed with the Securities and
Exchange Commission (SEC) from time to time and available at
www.sec.gov. These documents can be accessed on CalciMedica's web
page at ir.calcimedica.com/financials-filings/sec-filings. The
forward-looking statements contained herein are made as of the date
hereof, and CalciMedica undertakes no obligation to update them
after this date, except as required by law.
CalciMedica Contact:
Investors and
Media
Argot Partners
Sarah Sutton/Kevin Murphy
calcimedica@argotpartners.com
(212) 600-1902
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