Benzinga | Nov 4, 2021 08:34AM EDT

Processa Pharmaceuticals Announces Its Next Generation Capecitabine Inhibited DPD Activity 24-48 Hours After PCS6422 Administration; Co. Plans To Modify Phase 1b Trial

* Next Generation Capecitabine inhibited DPD activity 24-48 hours after PCS6422 administration with < 10% of 5-FU metabolized to FBAL compared to 80% reported for FDA approved capecitabine.

* 24-48 hours after PCS6422 administration, 5-FU potency based on systemic exposure per mg of capecitabine was at least 50 x greater than reported for FDA approved capecitabine.

* The improved metabolism profile and increased potency did not exist 7 days after PCS6422 administration.

* The timeline of DPD inhibition and de novo formation will be further evaluated in the existing study in order to identify PCS6422 regimens which may inhibit DPD throughout capecitabine dosing.

HANOVER, MD, Nov. 04, 2021 (GLOBE NEWSWIRE) -- 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."