Global Prostate Cancer Clinical Landscape Report 2021: Pfizer's Next-generation Androgen Receptor (AR) Inhibitor Xtandi is the Market Leader

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Jul 16, 2021, 08:15 ET

DUBLIN, July 16, 2021 /PRNewswire/ -- The "Disease Analysis: Prostate Cancer" report has been added to ResearchAndMarkets.com's offering.

The publisher 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 4.7%, 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 9.6 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.

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-naive 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.

Key Topics Covered:

OVERVIEW

Latest key takeaways

DISEASE BACKGROUND

Definition
Risk factors
Symptoms
Diagnosis
Prognosis
Patient segmentation
Clinical states

TREATMENT

Referral patterns
Localized prostate cancer
Locally advanced prostate cancer
Recurrent/progressive prostate cancer
Metastatic hormone-sensitive prostate cancer
Non-metastatic castration-resistant prostate cancer
Metastatic castration-resistant prostate cancer

EPIDEMIOLOGY

Incidence methodology

MARKETED DRUGS

PIPELINE DRUGS

KEY REGULATORY EVENTS

Oral Orgovyx Could Reduce Patients' COVID-19 Exposure Risk
Telix Takes Radiopharmaceutical Route To Prostate Cancer Market
AstraZeneca/Merck's Lynparza Gets Second Line Prostate Cancer Indication
Clovis's Rubraca Is First PARP For Prostate Cancer, But AZ's Lynparza Coming Soon
Myovant Submits First NDA For Relugolix, Plans Another In May
Trial Issues Complicate Tookad's Path To Approval
Steba's Tookad: US FDA Panel To Weigh Novel Endpoints, Missing Data And Toxicities

PROBABILITY OF SUCCESS

LICENSING AND ASSET ACQUISITION DEALS

Pfizer Gains New Commercial Drug Orgovyx In Deal With Myovant
Janssen, Xencor Team Up Against Prostate Cancer
Diaprost Obtains PSA Antibody IP From Memorial Sloan Kettering

CLINICAL TRIAL LANDSCAPE

Sponsors by status
Sponsors by phase
Recent events

DRUG ASSESSMENT MODEL

MARKET DYNAMICS

FUTURE TRENDS

Xtandi will remain the best-selling therapy over the next decade
Abiraterone generics have largely displaced Zytiga prescribing
Johnson & Johnson will rely on Erleada to offset Zytiga revenue losses
Prescribing of next-generation hormone therapies in earlier treatment settings will drive growth of the market
Pipeline drugs targeting mCRPC patients will generate only moderate uptake

CONSENSUS FORECASTS

RECENT EVENTS AND ANALYST OPINION