Callisto Pharmaceuticals, Inc. (AMEX: KAL; FWB: CA4), a developer of new
drug treatments in the fight against cancer and gastrointestinal
disorders, announced today promising interim data from the company´s
ongoing open-label Phase II clinical trial of Atiprimod to treat low to
intermediate grade neuroendocrine carcinoma (advanced carcinoid cancer).
Overall, the interim results suggest that Atiprimod is an active and
well tolerated drug in the treatment of carcinoid cancer.
In this interim analysis, 25 of 46 enrolled patients had sufficient data
available for evaluation. The median follow up of the patients was 6
months (range 2 to over 12 months). All patients enrolled in this study
had evidence of progressing disease in the 6 months preceding
enrollment. Details of this analysis will be presented at the 44th annual meeting of the American Society of Clinical Oncology (ASCO)
which will be held in Chicago May 30-June 3, 2008.
Interim analysis patient selection: The efficacy reporting includes all patients for which screening
baseline data and at least Cycle 2 RECIST measurements were available
as well as patients who had progressive disease before Cycle 2 at the
cut off time for the analysis. The safety reporting includes all
reported SAE information as of the cut off date for all 46 enrolled
patients.
Tumor response analysis: Of the
evaluable patients, 92% had stable disease as best response per standard
RECIST criteria, with a median duration of 6 months. Actuarial
progression free survival at 6 months is 76% and at 12 months it is 50%.
There were no objective RECIST responses for tumor regression in the
analyzed cohort. To date, 7 patients have completed all 12 planned
cycles of Atiprimod therapy with stable disease and have entered an
extension trial to continue treatment.
Symptom relief analysis: In this
analysis, 17 patients were evaluable for relief of symptoms of carcinoid
cancer (flushing, wheezing, diarrhea). 82% of patients responded with at
least 1 treatment cycle´s daily average
frequency of at least 1 symptom that was reduced by 20% or more from the
screening daily average for that symptom, as recorded by the patients in
a daily diary. The breakdown in responding symptoms were wheezing (2)
flushing (11) and diarrhea (5). (The number of symptom responses exceeds
the number of responding patients because some patients had more than
one symptom response.) Some of these symptom responses were quite
clinically striking and durable; for example, one patient had a steady
reduction in daily flushing frequency from nearly 6 episodes per day to
less than one episode per day by Cycle 7. This patient is continuing in
his 8th treatment cycle.
Side effect analysis: Serious
Adverse Events (SAE´s) from all 46 patients
enrolled in the study and reported to date have been analyzed. 15 SAEs
were reported in 13 unique patients. Nine of the 15 SAEs were assessed
as unrelated to Atiprimod by the treating investigator. Four SAEs were
assessed as possibly related, 1 as probably, and 1 as definitely
related. Of the 6 patients with SAEs assessed as possibly, probably, or
definitely related, all involved up to grade 4 AST/ALT elevations with
or without nausea and vomiting. Grade 1-2 bilirubin elevations were
noted in 3 of these. All of the 6 patients with SAEs of abnormal liver
function have recovered and 2 of these patients were able to
subsequently continue Atiprimod. Detailed dose modification guidelines
for liver function abnormalities are included in the protocol. Two SAEs
had an outcome of death "“ both were assessed
as unrelated to Atiprimod and involved complicated urinary tract
infections in elderly patients. Of the 13 remaining SAEs occurring in 11
unique patients in whom the outcome of the SAE was not death, 6 patients
discontinued study participation because of the SAE.
Study design: The study is an open
label Phase II study designed to evaluate the anti-tumor efficacy
effect on symptoms, safety and tolerability of Atiprimod over 12
treatment cycles (about 12 months) in patients with low to intermediate
grade neuroendocrine carcinoma (also called carcinoid cancer) who have
metastatic or unresectable cancer. Patients in the study must have
either progression of their cancer or symptoms from their carcinoid
tumor which is not controlled with standard octreotide therapy.
Forty-six patients were enrolled in the study, all of whom had
progressing disease in the six months preceding enrollment. In addition
patients were required to complete two weeks of a symptoms diary to
establish their symptoms baseline before commencing Atiprimod dosing.
Atiprimod is given orally according to a pharmacokinetically-driven
dosing regimen in 4-week cycles.
"We are pleased with the results that Atiprimod has shown so far in this
trial," said Dr. Gary S. Jacob, Chief Executive Officer of Callisto. "Importantly
in this slow growing cancer, Atiprimod has shown an ability to stabilize
disease progression and to reduce the symptoms of this disease, with a
side effect profile that is generally well tolerated, with reversible
increases in liver transaminases as the most notable adverse event. This
appears to be a drug that patients can tolerate for long term treatment
in this slowly progressing disease. We hope to be able to meet with the
FDA, sometime in the next twelve months, to discuss the design of a
pivotal Phase III trial."
Dr. Max Sung from the Mount Sinai School of Medicine in New York, the
lead investigator on the study, stated: "In
this interim analysis, Atiprimod has shown a clear trend towards
stabilizing patients who previously had progressive disease. This is a
very important finding and I believe that this drug has the potential to
become a first line therapy for this cancer."
Said Dr. Jacob: "This is the start of
realizing the potential of Atiprimod in various cancers. Carcinoid is an
excellent initial indication for Atiprimod. Importantly, the end point
in this trial, progression free survival, has been accepted by the FDA
as the primary endpoint for other recent phase III trials in this
disease. In addition to a phase III trial in carcinoid cancer, we will
also start to investigate possible designs of exploratory phase 2
programs in other cancers where we believe the drug has potential, such
as liver and colon cancer."
Atiprimod has been given orphan drug designation to treat carcinoid
cancer.
About Carcinoid cancer
Carcinoid tumors, or carcinoids, originate in hormone-producing cells of
the gastrointestinal (GI) tract, the respiratory tract, the
hepatobiliary (liver) system and the reproductive glands. The most
common site of origin is the GI tract, especially the small bowel. There
are about 7,000 new cases of carcinoid cancer diagnosed annually, with
the number increasing over the past 20-30 years. Carcinoid tumors that
metastasize to the liver have a poor prognosis. Traditionally
chemotherapy relieves symptoms in less than 30% of cases of metastatic
carcinoid tumors, usually for less than 1 year. Very few drugs that have
been tested in this cancer have shown clinically meaningful efficacy.
Carcinoid tumors often produce a condition called "carcinoid syndrome"
which is caused by the release of hormones from the tumors into the
blood stream. The symptoms vary depending on which hormones are released
by the tumors, but typically include diarrhea, facial flushing
wheezing, abdominal pain and valvular heart disease.
About Callisto Pharmaceuticals, Inc.
Callisto is a biopharmaceutical company focused on the development of
new drugs to treat various forms of gastrointestinal diseases and
cancer. Callisto´s drug candidates include two anti-cancer agents as
well as a drug for gastrointestinal disorders that is currently being
developed by its wholly-owned subsidiary, Synergy Pharmaceuticals. The
Company´s lead drug in the clinic, Atiprimod, is presently in a Phase II
clinical trial in advanced carcinoid cancer, a neuroendocrine tumor, and
in a Phase II extension trial in advanced carcinoid cancer patients.
Callisto´s second drug in the clinic, L-Annamycin, is currently in a
Phase I/II clinical trial in adult relapsed or refractory acute
lymphocytic leukemia, and in a Phase I clinical trial in children and
young adults with refractory or relapsed acute lymphocytic leukemia or
acute myelogenous leukemia. Synergy´s proprietary drug SP-304 is planned
to begin clinical development in 2Q2008 for gastro-intestinal disorders.
SP-304 is a synthetic analog of the human gastrointestinal hormone
uroguanylin, and acts by activating the guanylate cyclase C (GC-C)
receptor on epithelial cells of the colon. Callisto is also listed on
the Frankfurt Stock Exchange under the ticker symbol CA4. More
information is available at http://www.callistopharma.com.
Forward-Looking Statements
Certain statements made in this press release are forward-looking. Such
statements are indicated by words such as "expect," "should,"
"anticipate" and similar words indicating uncertainty in facts and
figures. Although Callisto believes that the expectations reflected in
such forward-looking statements are reasonable, it can give no assurance
that such expectations reflected in such forward-looking statements will
prove to be correct. As discussed in the Callisto Pharmaceuticals Annual
Report on Form 10-K for the year ended December 31, 2007, and other
periodic reports, as filed with the Securities and Exchange Commission
actual results could differ materially from those projected in the
forward-looking statements as a result of the following factors, among
others: uncertainties associated with product development, the risk that
products that appeared promising in early clinical trials do not
demonstrate efficacy in larger-scale clinical trials, the risk that
Callisto will not obtain approval to market its products, the risks
associated with dependence upon key personnel and the need for
additional financing