PharmaDrug Inc has revealed that its enteric-coated oral formulation of cepharanthine (PD-001), when combined with cabazitaxel, significantly reduces tumor volume, and provides improved prostate cancer tumor growth inhibition.-
As a result, the Toronto, Ontario-based specialty pharma company has filed a second provisional patent application to support new claims specifically related to the in vivo dosing of cepharanthine in combination with taxane-family members for the treatment of prostate cancer.
PharmaDrug said the provisional patent was filed on April 14, 2022, to support the use of PD-001 plus cabazitaxel for primary, metastatic, and chemotherapy-resistant prostate cancer.
In a statement, PharmaDrug CEO Daniel Cohen said: "With our new provisional patent filing, we continue to broaden the use case for PD-001 as a treatment for prostate cancer.”
“While esophageal cancer continues to be our main focus with a goal to move towards a United States Food and Drug Administration (FDA) clinical trial, we believe that cepharanthine will ultimately show a wider potential use in the treatment of cancers, specifically in combination with the current standard of care chemotherapies," he added.
In 2021, the company-initiated cancer screening studies aimed at uncovering therapeutic opportunities for cepharanthine when used alone or in combo with standard of care (SoC) chemotherapy drugs. Results from these in vitro studies revealed that the combination of cepharanthine and cabazitaxel, a SoC used for castration-resistant, metastatic prostate cancers, provided “unexpectedly synergistic reduction in prostate tumor cell survival.”
A once-per-day oral regimen of PD-001, with cabazitaxel provided a “statistically significant benefit” from day 10 through to the end of dosing (day 21) in its recently completed prostate efficacy study, said the company. Throughout the study period, the degree of tumor growth inhibition continued to improve for those groups receiving the PD-001 and cabazitaxel combo, versus cabazitaxel-alone, suggesting that perhaps a more sustained dosing regimen might result in greater efficacy.
On the completion of study dosing, PD-001 delivered at doses of 3, 9, or 27 mg/kg/day combined with cabazitaxel (3mg/kg/Q3D) provided up to a 64% tumor growth inhibition, compared to 37% noted for treatment with cabazitaxel alone, pointed out the company.
Based on the results, the addition of PD-001 to the SoC, cabazitaxel was found to improve tumor growth inhibition by 73%, compared to cabazitaxel-alone, it added. The results were deemed to be highly statistically significant, with a p-value less than 0.001 (day 21).
PD-001's strong promise
Cepharanthine is a natural product, approved for over 70 years in Japan to successfully treat chronic diseases. In clinical research, cepharanthine has exhibited anti-oxidative, anti-inflammatory, immuno-regulatory, anti-cancer, anti-viral and anti-parasitic effects. However, historically cepharanthine's low oral bioavailability been an obstacle.
PharmaDrug is advancing the clinical development of an improved and patented enteric-coated oral formulation of cepharanthine (PD-001) to treat responsive cancers and coronavirus (COVID-19). In comparison to generic cepharanthine, PD-001 has been shown in rodent and non-rodent models to be far more “easily absorbed”.
The findings support the development of an orally administered formulation and remove the requirement for frequent intravenous dosing to maintain therapeutic levels of the drug, noted the company. Despite research efforts, metastatic prostate cancer has a five-year survival rate of only 31%.
PD-001 for cancer
PharmaDrug said its cancer program is based on cepharanthine's known anti-cancer activities. Cepharanthine has been shown in multiple preclinical efficacy models 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 be a big challenge. However, Cepharanthine in preclinical studies has been able to “potently reverse” chemoresistance by downregulating expression of ABCB1, the transcript of which codes for multidrug resistance protein 1, (MDR1, aka P- glycoprotein), said the company.
Significantly, several prior in vitro and in vivo studies have shown that cepharanthine-mediated reductions in ABCB1 expression restores cancer cell sensitivity to a range of chemotherapeutics including taxanes, vinca alkaloids and platinum-based drugs. Collectively the two in vitro screening studies already completed by the company and the interim in vivo efficacy results, reinforce the potential opportunities in oncology for PD-001 when used in combination with prevailing treatments.
In addition to its ongoing investigations of PD-001 for prostate cancer, PharmaDrug said it plans to leverage the streamlined path to approval through Orphan Drug Designation for PD-001 for the treatment of esophageal cancer.
According to the American Cancer Society, in 2021, there were 248,530 new cases of prostate cancer and about 34,130 deaths from prostate cancer in US, and it’s the second leading cause of cancer death in American men. Metastatic prostate cancer is commonly treated using androgen deprivation therapy (ADT), including surgical or medical castration, but metastatic castration-resistant prostate cancer (mCRPC) commonly emerges.
PharmaDrug said its upcoming in vivo studies are "specifically designed" to address the potential of PD-001 to “overcome taxane-based chemoresistance in vivo”.
Contact the author Uttara Choudhury at uttara@proactiveinvestors.com
Follow her on Twitter: @UttaraProactive