Processa Pharmaceuticals Announces Next Generation Capecitabine (Combination of PCS6422 and Capecitabine) Inhibits DPD in Phase 1b Interim Analysis
04 Novembre 2021 - 1:15PM
Processa Pharmaceuticals, Inc. (NASDAQ: PCSA), (“Processa” or the
“Company”), a clinical-stage biopharmaceutical company developing
products to improve the survival and/or quality of life for
patients who have unmet medical need conditions, announced today
that the Company’s Next Generation Capecitabine dosage regimen (a
combination of PCS6422 administered with capecitabine) successfully
inhibited dihydropyrimidine dehydrogenase (DPD), altering the
metabolism of 5-fluoruracil (5-FU) at least during the first 24-48
hours after PCS6422 administration but not throughout the 7 days of
capecitabine dosing. If Next Generation Capecitabine inhibits the
metabolism of 5-FU throughout capecitabine dosing, the combination
product could be a more potent and safer cancer treatment than
current chemotherapy drugs including FDA approved capecitabine,
opening a multi-billion-dollar cancer chemotherapy market across
multiple types of cancer.
From the pharmacokinetic analyses of
capecitabine, 5-FU, and their metabolites on days 1 and 7 of
capecitabine treatment, the one-day dosing of PCS6422 irreversibly
inhibited dihydropyrimidine dehydrogenase (DPD) on day 1 of
capecitabine dosing in the first 2 Cohorts of the Phase 1b trial
resulting in: 1) less than 10% of 5-FU being metabolized to FBAL
compared to 80% reported with FDA approved capecitabine, 2) a
significantly longer half-life of 5-FU (i.e., 3-4 hours) than
reported for FDA approved capecitabine (i.e., 30-60 minutes), and
3) 5-FU potency based on exposure per mg of capecitabine
administered (i.e., AUC(0-inf)) being at least 50 x 5-FU potency
based on the exposure reported for current FDA approved
capecitabine.
There was little DPD inhibition found seven days
after PCS6422 dosing allowing the 5-FU from the Next Generation
Capecitabine to be metabolized to FBAL, similar to current FDA
approved capecitabine.
“Given the interim findings on the DPD activity,
the Company plans to modify the Phase 1b trial to not only
determine the MTD of capecitabine but also to further evaluate the
timeline of DPD inhibition and de novo formation in an effort to
define 6422 regimens which will maintain DPD inhibition throughout
capecitabine dosing,” said Dr. David Young, Chairman and CEO of
Processa. “Although in the first two cohorts, Dose Limiting
Toxicities (DLTs) did not occur and drug related adverse events
were only Grade 1 with no hand-foot syndrome noted, we will
postpone enrolling Cohort 3 in order to modify our Phase 1b
protocol and interact with the FDA regarding the modification of
our trial. The aims of our proposed modifications are to develop a
more precise timeline of DPD inhibition, DPD de novo formation, as
well as inter-patient variability. Processa will begin to collect
the data to individualize the treatment of Next Generation
Capecitabine for cancer patients, leading to a more personalized or
precision-based medicine approach.”
Next Generation Capecitabine (PCS6422 and
Capecitabine)
Capecitabine is one of the most widely used
chemotherapy agents in oncology and addresses a
multi-billion-dollar market. It is an oral prodrug of 5-FU that is
converted to 5-FU through a series of 3
metabolic steps. The problem with the current use of capecitabine, is that approximately 80% of
5-FU is broken down through catabolism to non-cancer killing
metabolites that may cause dose limiting side effects such as
hand-foot syndrome and cardiotoxicity while only 20% of 5-FU is
metabolized through successive phosphorylation steps to active
nucleotides which cause cell apoptosis and cancer cell death. Given
the catabolism is initialized through the DPD enzyme, PCS6422 (an
irreversible inhibitor of DPD) decreases the catabolism of 5-FU
resulting in more of the 5-FU being metabolized to active 5-FU
nucleotides which may lead to an increase in the cell death potency
of each mg of capecitabine administered. Thus, combining
capecitabine with PCS6422, results in lower amounts of capecitabine
needed to cause cellular apoptosis and death, making the
PCS6422-capecitabine combination a more potent Next Generation
Capecitabine.
The Next Generation Capecitabine (PCS6422
administered with capecitabine) Phase 1b trial (NCT04861987) is
multi-center, maximum tolerated dose trial. The Phase 1b trial is
designed to evaluate the change in the metabolism of 5-FU when DPD
has been inhibited and given the increased potency of capecitabine,
the maximum tolerated dose of capecitabine within the Next
Generation Capecitabine regimen. The metabolism and
pharmacokinetics of capecitabine, 5-FU, and their metabolites are
being evaluated as well as the dose limiting toxicities and adverse
event profile. Preliminary evidence of efficacy and further
confirmation of the safety of Next Generation Capecitabine will be
obtained in those patients who choose to continue Next Generation
Capecitabine.
More information on our clinical trials can be found on our new
website.
About Processa Pharmaceuticals,
Inc.
The mission of Processa is to develop products
with existing clinical evidence of efficacy for patients with unmet
or underserved medical conditions who need treatment options that
improve survival and/or quality of life. The Company uses these
criteria for selection to further develop its pipeline programs to
achieve high-value milestones effectively and efficiently. Active
clinical pipeline programs include: PCS6422 (metastatic colorectal
cancer and breast cancer), PCS499 (ulcerative necrobiosis
lipoidica) and PCS12852 (GI motility/gastroparesis). The members of
the Processa development team have been involved with more than 30
drug approvals by the FDA (including drug products targeted to
orphan disease conditions) and more than 100 FDA meetings
throughout their careers. For more information, visit the company’s
website at www.processapharma.com.
Forward-Looking Statements
This release contains forward-looking
statements. The statements in this press release that are not
purely historical are forward-looking statements which involve
risks and uncertainties. Actual future performance outcomes and
results may differ materially from those expressed in
forward-looking statements. Please refer to the documents filed by
Processa Pharmaceuticals with the SEC, specifically the most recent
reports on Forms 10-K and 10-Q, which identify important risk
factors which could cause actual results to differ from those
contained in the forward-looking statements.
For More Information:
Michael Floyd301-651-4256mfloyd@processapharmaceuticals.com
Jason Assad678-570-6791jassad@processapharmaceuticals.com
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