Processa Successfully Identifies Next Generation Capecitabine Dosage Regimens for Phase 2B Trial
01 November 2022 - 11:30PM
Processa Pharmaceuticals, Inc. (Nasdaq: PCSA), a diversified
clinical-stage company developing products to improve survival
and/or the quality of life for patients who have an unmet medical
need condition, announces positive results from its ongoing Next
Generation Capecitabine (NGC) Phase 1B trial. The data collected
has allowed Processa to estimate the timeline of dihydropyrimidine
dehydrogenase (DPD) irreversible inhibition and the formation of
new DPD after PCS6422 administration. NGC regimens (i.e., a variety
of PCS6422 regimens combined with a variety of capecitabine
regimens) were also identified that are safe with different
systemic and tumor exposure profiles to 5-FU. These findings will
allow Processa to evaluate multiple regimens with varying 5-FU
tumor exposures in the Phase 2B trial for the purpose of
identifying the NGC regimens that provide an improved
efficacy-safety profile over present therapy.
During the first 24 to 72 hours after
administration of PCS6422 in the Phase 1B trial, less than 10% of
the 5-FU was converted into the metabolites that only cause side
effects (i.e., catabolites), significantly less than the 80%
reported for FDA-approved capecitabine. The potency of NGC
(estimated from 5-FU systemic exposure) was approximately 50-times
greater than the potency of FDA-approved capecitabine. In addition,
the half-life of 5-FU after the initial administration of PCS6422
and capecitabine was found to be significantly greater at 2 to 6
hours versus the typical 5-FU half-life of approximately 45 minutes
after capecitabine administration.
Since 5-FU exposure is dependent on both the
PCS6422 regimen and the capecitabine regimen, Processa has
identified both NGC regimens that are safe as well as regimens that
cause dose-limiting toxicities as was seen with one patient in the
Phase 1B trial who had progressive stage 4 cancer. This patient had
Grade 4 neutropenia, was admitted to the hospital, and subsequently
died.
Dr. David Young, President and CEO of Processa,
stated, “We have identified NGC regimens that have potency
significantly greater than existing therapy and no dose-limiting
side effects, unlike existing capecitabine therapy where
approximately 25- 60% of the patients require dose modifications or
discontinuation. In addition, we understand the effect of different
NGC regimens on the timeline of DPD irreversible inhibition and a
patient’s production of new DPD, allowing us to better define the
relationship between various NGC dosage regimens, 5-FU exposure,
and the safety of NGC.”
Dr. Young added, “The next step will be to
demonstrate in a Phase 2B trial that these NGC regimens also have
better efficacy than existing therapy and, therefore, provide a
significant improvement in the benefit-risk profile over existing
therapy. We plan to use a Phase 2B trial to determine which
regimens provide this improved efficacy-safety profile over present
therapy using the principles of the FDA’s Oncology Project Optimus
initiative to help guide us in the design of the trial. In 2023
Processa plans to meet with FDA to discuss the design of our Phase
2B trial and initiate the trial.”
Next Generation Capecitabine
Next Generation Capecitabine (NGC) is a
combination of a PCS6422 regimen and a separate capecitabine
regimen. Capecitabine is a fluoropyrimidine, like 5-Fluorouracil
(5-FU) the major metabolite of capecitabine, that remains the
cornerstone of treatment for many types of cancers in an estimated
two million patients annually. Capecitabine is an oral pro-drug of
5-FU and approved as first-line therapy for metastatic colorectal
and breast cancer. The adverse effects of capecitabine such as the
development of Hand-Foot Syndrome from 5-FU catabolites (e.g.,
α-fluoro-β-alanine (F-Bal)) and neutropenia from 5-FU anabolites
(e.g., phosphate metabolites) can have severe adverse effects on a
patient’s daily activities, quality of life, and potentially
requiring dose interruptions-adjustments or therapy
discontinuation, all resulting in suboptimal tumor therapy.
PCS6422 is an oral, potent, selective, and
irreversible inhibitor of dihydropyrimidine dehydrogenase (DPD),
the enzyme that rapidly metabolizes 5-FU into catabolites which can
cause dose-limiting side effects. The formation of 5-FU anabolites
in cancer cells and normal cells is not dependent on DPD.
By combining the regimens of PCS6422 and
capecitabine, the change in 5-FU metabolism and, therefore,
elimination results in an increase in the potency of capecitabine
as determined by the systemic exposure of 5-FU per mg of
capecitabine administered. This results in requiring less
capecitabine to kill cancer cells and to treat each patient. To
date, Processa has found that the irreversible inhibition of DPD by
PCS6422 can alter the elimination of 5-FU making NGC significantly
more potent (greater than 50-times more potent) and potentially
leading to higher levels of the anabolites which can kill
replicating cancer and normal cells causing dose limiting side
effects such as neutropenia. By administering NGC to cancer
patients, the balance between anabolites and catabolites changes
depending on the dosage regimens of PCS6422 and capecitabine used,
making the efficacy-safety profile of NGC different than that of
FDA-approved capecitabine and requiring further evaluation of the
PCS6422 and capecitabine regimens to determine the optimal Next
Generation Capecitabine regimens for patients.
The projected market for NGC is $500 million to
$1 billion in the U.S. for the treatment of colorectal cancer and
over $1 billion within the U.S. for the treatment of the many
cancers that capecitabine is used. The potential worldwide market
for NGC for colorectal cancer exceeds $1 billion.
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 its
Regulatory Science Approach criteria when selecting drugs for
development to achieve high-value milestones effectively and
efficiently. Active clinical pipeline programs include: PCS6422
(metastatic colorectal cancer, breast cancer), PCS12852
(gastroparesis, functional constipation), and PCS499 (ulcerative
necrobiosis lipoidica). Members of the Processa development team
have been involved with more than 30 approvals for indications in
almost every division of the FDA (including drug products targeted
to orphan disease conditions) and more than 100 FDA meetings
throughout their careers. For more information, visit our 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 that 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
Floydmfloyd@processapharma.com(301) 651-4256
Patrick Lin(925)
683-3218plin@processapharma.com
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