Statistically significant 100% reduction (p =
0.0027) in new-onset severe respiratory failure and 64.2% reduction
(p = 0.0476) in new-onset persistent respiratory failure in
combined high and medium dose Auxora patients versus combined low
dose Auxora and placebo patients
Statistically significant stratified win ratio
of 1.640 (p = 0.0372) for high dose Auxora compared to
placebo
Clinically meaningful reduction observed for
high dose Auxora patients compared to placebo in additional key
endpoints: new-onset necrotizing pancreatitis and time to medically
indicated discharge
Conference call and webcast to review full
data set from the Ph2b CARPO trial to be held at 12 p.m.
ET/ 9 a.m. PT
LA
JOLLA, Calif., Oct. 30,
2024 /PRNewswire/ -- CalciMedica, Inc. (CalciMedica
or the Company) (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 is announcing
late-breaking positive data from the Phase 2b CARPO trial of Auxora™ in acute pancreatitis
(AP) with accompanying systemic inflammatory response syndrome
(SIRS) at the American College of Gastroenterology (ACG) 2024
Annual Scientific Meeting in Philadelphia, PA and virtually. Prof.
Robert Sutton from the University of Liverpool and Liverpool University Hospitals NHS Foundation Trust
and chair of the Steering Committee for the CARPO trial will
deliver a plenary presentation entitled "A Randomized,
Double-Blind, Placebo Controlled Dose Ranging Study of Auxora in
Patients with Acute Pancreatitis (AP) and Accompanying Systemic
Inflammatory Response Syndrome (SIRS) - CARPO."
"With the data being presented here at ACG, we see that Auxora
continues to deliver across key AP endpoints, showing that the drug
substantially reduced respiratory failure, necrotizing
pancreatitis, and long hospital stays, which may in turn minimize
patient mortality and morbidity as well as the economic burden of
this disease," said Prof. Robert
Sutton. "The reduction of severe respiratory failure is
particularly clinically meaningful as respiratory failure is the
main driver of mortality in AP patients. These data demonstrate
that Auxora may be an important new tool in a critical illness with
no approved therapies, and we are encouraged as we look ahead to
the Phase 3 trial of Auxora in AP patients with SIRS."
"CARPO has delivered results that mirror those from previous
Phase 2 trials of Auxora in other acute critical diseases and
represents a significant step forward for the development of CRAC
channel inhibitors in these diseases," said Sudarshan Hebbar, M.D., Chief Medical Officer
of CalciMedica. "The CARPO results highlight Auxora's unique
immunomodulatory action coupled with direct organ tissue
protection, most importantly in the lung, and provide an optimistic
readthrough to the acute kidney injury, or AKI, setting, where
respiratory failure is also a significant cause of mortality. With
these data, we are even more encouraged about KOURAGE, our Phase 2
trial in AKI patients with respiratory failure, which we expect to
read out next year."
CARPO Trial Design
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.
CT scans to evaluate pancreatic inflammation and necrosis were
performed at study entry and at 30 days. Patients were stratified
by baseline hematocrit, a biomarker for inflammation severity,
and 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.
Efficacy & Safety Data Presented at the ACG Annual
Scientific Meeting
At ACG, Prof. Sutton will be discussing CARPO endpoints
previously reported in June, including median time to solid food
tolerance (up to a 50 hour reduction for Auxora patients compared
to placebo) and severe organ failure including both respiratory and
renal failure (up to 61.7% relative risk reduction for Auxora
patients compared to placebo), and presenting new data from
additional endpoints. The new data includes an integration of key
endpoints of the trial into a win ratio analysis, providing a
comprehensive evaluation of Auxora for the treatment of AP with
SIRS.
- New-onset severe respiratory failure, defined as (i) receiving
invasive mechanical ventilation or (ii) use of either high-flow
nasal cannula or non-invasive mechanical ventilation for 48 hours
or longer, occurred in 0% of high dose patients, 0% of medium dose
patients, 8.3% of low dose patients, and 8.5% of placebo patients,
representing a 100% (p = 0.0027) relative risk reduction
when combined high and medium dose patients were compared to
combined low dose and placebo patients.
- New-onset persistent respiratory failure, defined as (i) severe
respiratory failure or (ii) not severe respiratory failure but
PaO2 /FiO2 of 300 or lower for 48 hours or
longer and use of low-flow oxygen support, occurred in 8% of high
dose patients, 1.9% of medium dose patients, 10.4% of low dose
patients, and 17% of placebo patients, representing a 64.2% (p =
0.0476) relative risk reduction when combined high and medium dose
patients were compared to combined low dose and placebo
patients.
- New-onset necrotizing pancreatitis, measured on day 30,
occurred in 29.7% of high dose patients, 40.8% of medium dose
patients, 38.6% of low dose patients, and 37.0% of placebo
patients, representing a relative risk reduction of approximately
20% for high dose patients compared to placebo patients.
- Median time to medically indicated discharge, defined as (i) no
clinical evidence of infection necessitating continued
hospitalization, (ii) solid food tolerance, and (iii) abdominal
pain resolved or controlled with non-opiate medications, was 89.0
hours for high dose patients, 104.5 hours for medium dose patients,
109.5 hours for low dose patients, and 104.0 hours for placebo
patients, demonstrating a reduction of 15.0 hours for high dose
patients when compared to placebo.
- Long hospital stays were reduced in combined high and medium
dose patients compared to combined low dose and placebo patients,
with 18% vs 31% of patients in the hospital longer than 7 days, 5%
vs 10% longer than 14 days, and 1% vs 6% longer than 21 days,
respectively. There were no high dose patients who stayed in the
hospital longer than 21 days.
- When key endpoints—all-cause mortality, new-onset severe
respiratory failure, new-onset necrotizing pancreatitis, and time
to medically indicated discharge—were integrated into a win ratio
analysis, the high dose of Auxora outperformed placebo by a similar
margin across all endpoints and delivered a stratified win ratio of
1.640 (p = 0.0372).
As in prior Phase 2 trials, Auxora provided patients with
clinically meaningful improvement and was well-tolerated. There was
a trend of decreasing treatment emergent serious adverse event
(TESAE) rates with increasing doses of drug. Additionally, there
were no drug-related TESAEs or deaths in patients receiving the
high dose of Auxora.
"AP is a complex inflammatory syndrome that currently has no
approved therapies, leaving a significant unmet medical need for
patients and hospital systems," said Rachel
Leheny, Ph.D., Chief Executive Officer of CalciMedica.
"With CARPO, we believe we have now identified the most effective
dose of Auxora for AP patients and have clarified how best to
measure the drug's benefit to these patients. Given the complexity
of issues that these patients experience, we are encouraged that
the 2.0 mg/kg Auxora dose delivered a statistically significant
1.640 stratified win ratio compared to placebo. We plan to meet
with the FDA to discuss the design of a Phase 3 trial of Auxora in
patients with AP with accompanying SIRS."
The Company will be hosting a conference call and webcast on
Wednesday, October 30, 2024 at
12 p.m. ET/ 9
a.m. PT, during which Prof. Robert
Sutton will deliver his plenary presentation from the ACG
Annual Scientific meeting. To join, follow the instructions
below.
Participant Webcast
Link: https://app.webinar.net/4EanW4A2PXk
Click on the webcast link and complete the
online registration form.
Upon registering, you will be connected to the
online webcast.
Participant Dial-in Numbers: 1-646-357-8785 (US) and
1-800-836-8184 (international)
If prompted by the operator, ask to join the
CalciMedica Phase 2b CARPO Full Data
Set & Win Ratio call.
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
has demonstrated positive and consistent clinical results in
multiple completed efficacy clinical trials, including a Phase
2b trial (called CARPO) in patients
with AP with SIRS and a Phase 2 trial (called CARDEA) in patients
with COVID pneumonia. Auxora is currently being evaluated in a
Phase 2 trial in acute kidney injury (AKI) with associated acute
hypoxemic respiratory failure (AHRF), called KOURAGE, and 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 300,000 U.S. patients
hospitalized for AP annually, with an estimated 100,000 with
accompanying 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 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 announced data for a Phase
2b trial (called CARPO
– NCT04681066) in patients with AP with SIRS and completed a
Phase 2 trial (called CARDEA – NCT04345614) in patients with
COVID pneumonia. The Company is currently conducting a Phase 2
trial (called KOURAGE – NCT06374797) in patients with AKI with
associated AHRF with data expected in 2025 and continuing to
support the ongoing Phase 1/2 trial (called CRSPA
– NCT04195347) in patients with AIPT 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,
CalciMedica's business strategy; the potential benefits of Auxora
for treatment of AP patients and the healthcare system, including
its potential to address the significant disease burden of AP; the
estimated patient population and demographics of patients with AP;
the Company's target patient population in AP and the likely drug
dose of Phase 3 trial of Auxora for the treatment of AP;
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 Phase
2 KOURAGE trial of Auxora in AKI with associated AHRF, its
ongoing Phase 1/2 CRSPA trial of Auxora in pediatric patients with
AIPT and its planned Phase 3 trial of Auxora for AP with
accompanying SIRS; plans for an end of Phase 2 meeting with the FDA
for CARPO; the potential benefits of Auxora for the
treatment of AP, AKI and AIPT; 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; the impact of government laws and regulations; and
CalciMedica's financial position and need for additional capital.
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 June 30, 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
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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SOURCE CalciMedica, Inc.