PharmaDrug Inc (CSE:PHRX, OTCQB:LMLLF) said it has completed significant groundwork to support multi-kilogram production for use in the final drug production of PD-001, its patented, oral version of cepharanthine, to treat responsive cancers and COVID-19.
Completion of this lot, slated for September 2022, advances PharmaDrug’s plans to potential phase 2 clinical studies.
PharmaDrug has engaged Genvion Corporation to complete stability testing and forced degradation studies in support of future investigational new drug (IND) filings to the US Food and Drug Administration (FDA).
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Genvion Corporation will take receipt of the current good manufacturing process (cGMP) drug substance and complete the manufacturing efforts necessary to produce the orally bioavailable clinical drug product, PD-001.
Daniel Cohen, CEO of PharmaDrug said the source and subsequent characterization of bulk materials, including generic cepharanthine, followed by the preparation of cGMP calibre analytical methodologies as required by the FDA, represents the majority of the effort in this initial production effort.
“With these activities now complete, we are positioned to initiate the cGMP manufacturing run of our lead candidate, PD-001. Achieving this milestone represents an important inflection point in our preclinical and clinical development programs in oncology and infectious disease," Cohen said in a statement.
After receiving a written response regarding its plan for PD-001, PharmaDrug has worked on feedback, specifically related to necessary chemistry and manufacturing controls set forth by the regulator, to advance its preclinical development programs for PD-001 as a potential treatment for infectious disease and prostate and esophageal cancers.
Cepharanthine is a natural product and an approved drug used for more than 70 years in Japan to successfully treat a variety of acute and chronic diseases. In clinical research, cepharanthine exhibits anti-oxidative, anti-inflammatory, immuno-regulatory, anti-cancer, anti-viral and anti-parasitic effects. However, cepharanthine's low oral bioavailability has represented a major obstacle to its full clinical potential.
PharmaDrug is focused on the clinical development of an improved and patented enteric-coated oral formulation of cepharanthine in PD-001, which has been shown in animal models to possess markedly improved oral bioavailability.
PharmaDrug's oncology program is based on cepharanthine's known anti-cancer activities. Cepharanthine has been shown in peer-reviewed publications to inhibit cancer cell proliferation, induce cancer cell apoptosis (death) and restore cancer cell sensitivity to multiple unrelated classes of chemotherapy.
Multidrug resistance continues to represent a considerable clinical challenge. As such, preclinical cancer studies aimed at explaining the mechanisms that underlie chemoresistance are of particular interest to PharmaDrug. Cepharanthine has been shown in preclinical studies to potently reverse chemoresistance.
A previous IND-enabling efficacy study commissioned by PharmaDrug demonstrated that a once-per-day oral regimen of PD-001, in combination with standard of care (SoC), chemotherapy drug cabazitaxel provided statistically significant benefit from day 10 through to the end of dosing on day 21, with up to 73% tumor growth inhibition.
Based on the data, PharmaDrug has filed two provisional patent applications, which support use of PD-001 plus cabazitaxel for primary, metastatic and chemotherapy-resistant prostate cancer.
The company also plans to use its FDA Orphan Drug Designation PD-001 for the treatment of esophageal cancer. The company previously announced that a once-per-day oral regimen of PD-001, in combination with a SoC chemotherapeutic drug, paclitaxel, significantly reduced tumor volume and improved tumor inhibition at the scheduled end of dosing (day 28 post implantation) in its recently completed esophageal cancer efficacy study.
Third parties have identified cepharanthine as a forerunner in the treatment of SARS-CoV-2, the virus that causes COVID-19. In fact, cepharanthine has been shown to be highly effective at blocking cell death following exposure to multiple different coronaviruses, including COVID-19, lab-attenuated SARS-CoV (original SARS) and the virus that causes Middle East respiratory syndrome (MERS)7-9.
In November 2021, an independent research group examined the potential of cepharanthine to limit the cytopathic effects of the South African COVID-19 variant, B.1.351. It was found that cepharanthine was at least six times more active against the South African variant strain than original SARS-CoV-2, and that cepharanthine was the most effective of all the drugs.
Although the recent Omicron variant discovered in South African nations shares several features in common with the previous South African variant, B.1.351, it remains to be determined how well cepharanthine will perform at treating this emerging threat.
Intriguingly, the same authors also noted that cepharanthine displayed significant potency with a favorable selectivity index for other RNA viruses including Zika and Ebola10.
Despite the promising findings for cepharanthine, translation into clinical application has been hampered by the need for the generic formulation of the drug to be delivered intravenously due to its intrinsically poor oral bioavailability.
PharmaDrug intends to develop and commercialize PD-001 as an oral antiviral treatment for patients with mild to moderate SARS-CoV-2 infection.
Contact the author at susie@proactiveinvestors.com