PRL-02 (injectable abiraterone decanoate)
Surgical and chemical castration (e.g., Lupron Depot®, leuprolide acetate for depot suspension) are standards of care for metastatic prostate cancer (PC) but androgens produced in the adrenals, prostate, and the tumor itself can continue to drive tumor growth. The treatment goal for advanced disease is to block androgen receptor (AR) activation by these extra-gonadal androgens (e.g., testosterone). Current treatments for advanced or high-risk PC are suboptimal due to limited efficacy, safety, or compliance. Though several AR antagonists are approved for the treatment of PC, only one product (Zytiga®, abiraterone acetate) with a potentially superior MOA (i.e., inhibition of CYP17, the enzyme that produces androgens) is available. However, the oral abiraterone acetate regimen is complex and has safety and efficacy concerns, leading to patient compliance concerns.
Moreover, the Zytiga® 1,000mg daily dose maximally inhibits CYP17 hydroxylase; however, CYP17 lyase is the target enzyme activity (see the Figure below). Maximal inhibition of CYP17 hydroxylase is associated with safety concerns with warnings tht are cited on the Zytiga® label.
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Abiraterone decanoate and PRL-02 were created by Propella scientists. Following intramuscular (IM) injection of PRL-02, abiraterone decanoate is routed through the lymph to target tissues where it releases the precise level of abiraterone needed to block CYP17 lyase for 12 weeks, thereby reducing interim tumor breakthrough risk. PRL-02, like Zytiga®, targets the AR signaling pathway, specifically by blocking the the CYP17 enzyme that produces androgens, thus preventing downstream AR activation. Results to date indicate that PRL-02 doses sufficiently and preferentially inhibit CYP17 lyase without profound effects on CYP17 hydroxylase.
Emerging clinical data suggest an improved efficacy and a vastly improved safety profile versus standard of care Zytiga®, while being significantly more convenient for patients. Efficacy and safety advantages versus Zytiga® are hypothesized to be due to no or minimal CYP17 hydroxylase inhibition, which causes the symptoms of mineralocorticoid excess (e.g., hypertension and hypokalemia) and drives tumor resistance.
Click image to enlarge.
PRL-02 (abiraterone decanoate) is currently in a Phase 1 dose-escalation study in patients with advanced PC and is expected to enter the Phase 2a portion of the study in the first half of 2023.
For further information, please see Propella’s presentation at the European Society for Medical Oncology Congress in Paris, France on September 11, 2022 (click here).
CGS-200-5
There are currently no approved therapies that effectively manage moderate to severe osteoarthritis (OA) pain without significant concerns related to tolerability, safety, or addiction potential. Topical CGS-200-5 (5% capsaicin) has clinically been shown to significantly reduce OA knee pain. In a Phase 2 study, CGS-200-5 reduced pain by 50% (based on WOMAC pain score) while demonstrating good safety and tolerability. CGS-200-5 also demonstrated highly durable pain relief. Patients on average reported diminished pain through 90 days, the final time point of the Phase 2 study, following just four consecutive days of topical treatment at study start. Acknowledging the therapeutic potential of topical high-concentration capsaicin, the American College of Rheumatology recently revised its OA treatment guideline to conditionally recommend topical capsaicin for knee OA pain.
