Prostate Cancer Disease Coverage Forecast and Market Analysis to 2036

Disease Overview

Prostate cancer is a hormonally fueled disease, and the most common form of cancer found in males. Consequently, there is a high incentive for drug development in this indication due to its large population size. While hormone-sensitive prostate cancer is well managed in terms of treatment options, unmet need persists for patients with prostate cancer that is no longer responsive to hormonal manipulation. Newly approved therapies for castration-resistant prostate cancer are set to create a shift in the way that the disease is treated, while creating a competitive environment for new market entrants.

Latest key takeaways

• Datamonitor Healthcare estimates that in 2018, there were 1.3 million incident cases of prostate cancer worldwide in males aged 40 years and older, and forecasts that number to increase to 1.5 million cases by 2027.
• In the US, prostate cancer is the most common non-cutaneous malignancy diagnosed in men, and is the second-leading cause of cancer mortality in men behind lung cancer.
• The overall likelihood of approval of a Phase I prostate cancer asset is 4.9%, and the average probability a drug advances from Phase III is 51.5%. Prostate cancer drugs, on average, take 9.0 years from Phase I to approval, compared to 9.5 years in the overall oncology space.
• Pfizer’s next-generation androgen receptor (AR) inhibitor Xtandi is the market leader in prostate cancer due to its established efficacy across prostate cancer segmentations and a lack of near-term generic competition. Bolstered by recent and planned expansions into additional prostate cancer segments, Xtandi will continue to be the leading option in this indication. Future expansion opportunities include potential use in combination with PARP inhibitors Talzenna or Rubraca in metastatic castration-resistant prostate cancer (mCRPC) patients. Xtandi is also being trialed in combination with leuprolide in the Phase III EMBARK study for non-metastatic hormone-sensitive prostate cancer patients progressing on definitive therapy. Potential expansion into this segment represents a significant opportunity to improve outcomes earlier in the treatment paradigm, but the combination will have to demonstrate a significant benefit over existing localized treatment options to justify the additional clinical and financial toxicity of Xtandi treatment.
• Since the launch of generic abiraterone in the US in November 2018, sales of Johnson & Johnson’s cytochrome P450c17 inhibitor Zytiga have begun to erode. Further generic erosion is expected in the EU and Japanese markets in the next few years, decimating sales of the multi-blockbuster. Although branded Zytiga will continue to decrease in market share, use of abiraterone as part of standard regimens will continue and may expand to include several novel combinations.
• The PARP inhibitors Rubraca and Lynparza were both approved in the US in May 2020 for the treatment of mCRPC patients following AR inhibitor therapy. Rubraca received accelerated conditional approval in mCRPC with a deleterious BRCA mutation (germline and/or somatic), while Lynparza received full approval for use in the broader homologous recombination deficient (HRD) population. To potentially differentiate the PARP assets, both are being trialed in the first-line setting of mCRPC; Rubraca in combination with Xtandi against Xtandi alone, and Lynparza with abiraterone against abiraterone alone. There is potential synergy with these combinations as its hypothesized that AR inhibitors may sensitize tumors to PARP treatment by reducing DNA damage repair (DDR) expression.
• Late-phase PARP inhibitors Zejula and Talzenna are also being developed in combination with next-generation treatments and will join a crowded PARP treatment space. Zejula is being tested in combination with abiraterone against abiraterone alone as first-line therapy for mCRPC patients. Similarly, Talzenna is being studied in combination with physician’s choice of Xtandi or enzalutamide in mCRPC patients, also as a first-line option. The potential synergy of the PARP inhibitors with AR modulators is promising, but a strong benefit will have to be seen to justify use in the front-line setting of mCRPC. If approved, it is likely that these regimens will be limited to the HRD or even BRCA populations, where they will have strong utility but somewhat limited commercial impact due to the relatively small prevalence of these biomarkers.
• Next-generation AR inhibitors Nubeqa and Erleada have shifted the treatment paradigm to include these therapies in earlier segments of disease such as non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC). Expansion into earlier segments and lines of therapy is ongoing. Bayer is looking to expand Nubeqa’s label to include use in very high-risk localized patients and metastatic hormone-sensitive patients. Johnson & Johnson will continue to try and differentiate Erleada with an aggressive development plan that includes potential expansions into chemotherapy-naïve mCRPC patients as part of a combination with abiraterone, as well as into the localized setting for patients treated with prostatectomy or radiation therapy.
• Akt inhibitors ipatasertib and capivasertib are a potential new mechanistic addition to the prostate cancer space, but the efficacy/tolerability profile of these PI3K/Akt/mTOR pathway inhibitors may prevent approval and potential usage.  Ipatasertib is a pan-Akt inhibitor from Roche currently in development for asymptomatic or mildly symptomatic mCRPC patients with PTEN loss as part of a combination with abiraterone. PTEN loss is not a standard target in this indication, but represents a significant market opportunity as it is estimated to occur in approximately 20% of primary prostate cancers and up to 50% of castration-resistant tumors. However, ipatasertib is beset by known class toxicities of PI3K/Akt/mTOR pathway inhibitors such as diarrhea, rash, and ALT/AST elevations that could be detrimental to its regulatory chances. AstraZeneca’s Akt inhibitor capivasertib has also demonstrated mixed results in prostate cancer. In the Phase I/II ProCAID trial, capivasertib in combination with docetaxel failed to meet the primary endpoint of improved progression-free survival in mCRPC patients. However, the combination did improve overall survival in these patients irrespective of PI3K/Akt/mTOR pathway mutations. This has led to initiation of the Phase III CAPItello-281 trial testing capivasertib in combination with abiraterone in de novo mHSPC with PTEN loss.
• Several checkpoint inhibitors are in development for prostate cancer, but late-phase data from ongoing combination trials are needed to fully determine their relative outlook in the indication. Merck is pursuing an aggressive late-phase development strategy for Keytruda in prostate cancer that includes combinations with Lynparza, Xtandi, and docetaxel for the treatment of mCRPC patients. Opdivo is also in late-phase development as part of a combination with docetaxel in mCRPC patients after failure on a next-generation hormone therapy. Finally, Roche’s Tecentriq, the lone anti-PD-L1 antibody in late-phase development for prostate cancer, is currently in Phase III development in combination with Xtandi or in combination with Cabometyx in mCRPC patients after failing on a next-generation hormone therapy.
• Myovant’s relugolix is a GnRH receptor antagonist that is differentiated from available GnRH antagonist Firmagon by its oral formulation, which will facilitate use in patients undergoing localized definitive therapy who also need ADT and may also allow use of an intermittent ADT option in advanced hormone-sensitive patients looking to mitigate side effects and maintain quality of life.