Prostate Cancer Therapies

Abstract Number - 5001

Novartis to present subgroup analysis of Pluvicto, its first approved radioligand therapy in PSMA-positive mCRPC

In March 2022, Pluvicto (177Lu-PSMA-617) became the first FDA-approved targeted radioligand therapy (RLT) for eligible patients with mCRPC that combines a targeting compound (ligand) with a therapeutic radioisotope. The FDA approval was based on a pivotal Phase III VISION trial, where patients with pretreated PSMA-positive mCRPC who received Pluvicto plus standard of care had a statistically significant reduction in risk of death; both alternate primary endpoints of overall survival and radiographic progression-free survival were met.

The company is now shifting its focus on the subgroup analysis part of Pluvicto in mCRPC that will be presented on June 5, 2022, at ASCO 2022 Conference as an Oral Presentation. Another radiopharmaceutical drug which is developed by Point Biopharma, 177Lu-PNT2002 (PNT2002), is a PSMA-targeted therapy for mCRPC combining a PSMA-targeted ligand, PSMA-I&T, with the beta-emitting radioisotope lutetium-177. The company published academic data to advance directly into a Phase III clinical development program. They are focusing on evaluating superiority to the standard of care in mCRPC patients, and the top-line data for the Phase III trial is expected in Q3 2023.   

Abstract Number - 5016

Modra Pharmaceuticals to present Phase II data of oral docetaxel plus ritonavir (ModraDoc006/r) in patients with mCRPC

In February 2022, Modra Pharmaceuticals announced positive data from its Phase IIb trial evaluating its boosted oral taxane therapeutic, ModraDoc006/r, in patients with mCRPC compared to the standard-of-care, the IV chemotherapy docetaxel. Moreover, the pivotal study for ModraDoc006/r in patients with mCRPC is in development.

The first-line options for treatment of metastatic CRPC are numerous, and the decisions made are based on the treatments the patient has had prior, either for nmCRPC or for mHSPC. For example, patients who have had treatment with intensified ADT for mHSPC with abiraterone, enzalutamide, or apalutamide should receive a different approach for mCRPC; usually, the recommended treatment is docetaxel chemotherapy (Intravenous) and an ADT combination in that first-line setting.

Furthermore, the trial assessing ModraDoc006/r administered orally to improve the outcomes in mCRPC is ongoing. This explains the importance of providing alternative therapeutic options in first-line therapy for mCRPC, which can drive the market growth and be the alternative treatment option for the patients affected by mCRPC.

Abstract Number - 5049

Veru Pharma to present the final analysis of Phase Ib/II trial of sabizabulin in men with mCRPC who progressed on an androgen receptor targeting agent.

 A Phase Ib/II trial is evaluating sabizaulbin in patients with mCRPC who progressed on an androgen receptor targeting agent. Veru Pharma will present the final analysis of this Phase Ib/II study. In February 2022, Veru presented updated clinical data from the positive Phase Ib/II study of sabizabulin (VERU-111) in 80 men with mCRPC who have progressed on at least one novel androgen receptor-targeting agent at the ASCO GU Cancers Symposium 2022.

In this updated presentation, sabizabulin treatment demonstrated both cytotoxic and cytostatic antitumor activity. For patients with measurable disease at baseline (n = 29), the ORR was 20.7%. The best clinical response (stable disease or objective tumor response) in patients with measurable disease at study entry was 59% (17/29). This Phase Ib/II clinical study supports the efficacy and safety assumptions for the ongoing Phase III VERACITY clinical study evaluating sabizabulin in metastatic castration and androgen receptor targeting agent-resistant prostate cancer before IV chemotherapy. Excitingly, Veru is geared up to present the final analysis of sabizabulin on June 6, 2022, at ASCO 2022 Conference through Poster Session.

Abstract Number - 5078

Post NDA acceptance, Bayer is all set to present the data from the Phase III ARASENS trial

 In May 2022, US FDA accepted supplemental new drug application (sNDA) and granted Priority review for darolutamide in combination with docetaxel for mHSPC. The application is being conducted under the FDA Oncology Center of Excellence’s (OCE) Project Orbis initiative, which provides a framework for concurrent submission and review of cancer treatments among participating international health authorities. It would be interesting to know about the efficacy parameters for mHSPC after it receives the priority review.

Nubeqa (darolutamide) is already approved in the non-metastatic prostate cancer setting and now eyes the metastatic setting as well, both in CSPC and CRPC. Considering the recent positive efficacy results of Nubeqa in combination with Docetaxel and ADT, the company is expected to move ahead with the regulatory filing for further label expansion of this drug in HSPC. We expect the drug to face competition from the already existing Xtandi and Erleada along with the recently approved Relugolix.

CONCLUSION

Prostate cancer is the second leading cause of cancer-related death in American men. Earlier, most of the attention in the field of advanced prostate cancer was restricted to the research and development of drugs for patients with CRPC, even though CSPC is burdened with poor prognosis and impaired quality of life. However, recent years have witnessed an expansion in the field of mCSPC as companies such as Bayer has now shifted its focus to mCSPC, which is a less crowded market when compared to CRPC. nmCRPC was the first segment in Prostate cancer that Nubeqa received an approval for. Nubeqa is expected to face stiff competition with Erleada and Xtandi (in both nmCRPC and mCSPC), where Xtandi is expected to lose patent by the year 2027 leading to entry of generics. Needless to mention, Xtandi has already gained its fair share of benefit by reaching approximately USD 4 billion in sales in the year 2020.

Moving on to the CRPC market which is already quite crowded, we await for the final results of Veru Pharma’s Sabizabulin, which is all set to present it final Phase Ib/II data. Howver, we still need to figure out of Modra Pharma can replace the IV docetaxel with its oral one.

Other Companies such as Merck Sharp & Dohme (Keytruda/pembrolizumab), Pfizer (Talazoparib), Janssen (Niraparib), Clovis Oncology (Rubraca), Bristol-Myers Squibb (Opdivo), Exelixis (Cabozantinib), AstraZeneca (Capivasertib), and Genentech (Tecentriq) are also investigating their novel products for the management of mCSPC/mHSPC or studying how to better use existing treatment options.

The rest of the key abstracts are summarized in the table below: