DRugwatch BlogRSS 2.0

DRugwatch Blog > September 2010 > A Turbulent Time in Castrate-Resistant Prostate Cancer – Success and Failures of Late-Stage Emerging

A Turbulent Time in Castrate-Resistant Prostate Cancer – Success and Failures of Late-Stage Emerging Therapies

Andrew MerronWritten by: Andrew Merron

SUMMARY
The late-stage clinical pipeline for Prostate Cancer (CaP) is diverse and dynamic: news concerning three high-profile emerging agents in Phase III trials for CaP were released during September 2010.

  • On September 9th, Johnson & Johnson announced that the pivotal Phase III trial for abiraterone in chemotherapy-pretreated, metastatic, castrate-resistant CaP (MCRPC) was unblinded based on advice from the Independent Data Monitoring Committee (IDMC). There was a statistically significant improvement in overall survival (OS) in the pre-specified interim analysis.
  • On September 27th, AstraZeneca announced that zibotentan failed to significantly improve OS in a pivotal Phase III study in asymptomatic/minimally symptomatic MCRPC.
  • Finally, also on September 27th, Pfizer announced that the pivotal Phase III trial of Sutent in combination with prednisone for Taxotere-treated MCRPC patients has been discontinued because Sutent would unlikely improve OS.

ANALYSIS
Abiraterone is a highly promising emerging therapy for MCRPC. Decision Resources had forecasted a launch of abiraterone, the recent positive top-line OS results only confirm this agent is still on track to approval. Full data are not yet available but will be presented at the European Society for Medical Oncology (ESMO) conference next month. We forecast abiraterone will be a clinically and commercially successful agent in the treatment of MCRPC, but it also has potential to be used in earlier lines of treatment. Initially, abiraterone will be prescribed to MCRPC patients who have previously received chemotherapy, in this setting it will join Sanofi-Aventis’ newly FDA-approved chemotherapy, Jevtana (cabazitaxel). We forecast that abiraterone will also be approved in first-line asymptomatic/minimally symptomatic MCRPC, where it will compete with Dendreon’s Provenge (sipuleucel-T) for patient share. It is unlikely these two agents will be used concurrently because of the chronic administration of prednisone (an immunosuppressive agent) (a requirement for abiraterone) may reduce the efficacy of Provenge. Oral delivery, proven mechanism of action, and likely lower cost of abiraterone compared with Provenge will help drive uptake of abiraterone in this setting.

Conversely, the failure of zibotentan in asymptomatic/minimally symptomatic MCRPC means zibotentan will not compete with Provenge or abiraterone. Decision Resources forecasted that zibotentan would not launch in this setting, however despite the recently announced failure, two further Phase III trials for zibotentan are ongoing in the ENTHUSE (Endothelin-A Use) clinical program. The failure of zibotentan to significantly improve OS in asymptomatic/minimally symptomatic MCRPC in Phase II and Phase III trials may be due to short treatment durations. Therefore, hope remains for zibotentan in non-metastatic CRPC (as a single agent) and in first-line MCRPC (in combination with Taxotere) because zibotentan will likely be given for extended durations.

Pfizer’s pivotal Phase III trial for Sutent has been discontinued in the chemotherapy-pretreated MCRPC setting. The SUN-1120 trial was evaluating Sutent in combination with prednisone in Taxotere-pretreated MCRPC patients. The trial was discontinued based on advice from the IDMC because OS would unlikely be significantly improved. Decision Resources had forecasted that Sutent would not launch for MCRPC. The failure of Sutent follows in the wake of the March 2010 news that Roche/Genentech/Chugai’s Avastin (bevacizumab) failed to significantly improve OS in first-line MCRPC setting in combination with Taxotere/prednisone. The failure of Sutent further highlights the questionable role of angiogenesis inhibition in the treatment of advanced CaP. Although high unmet need for improving OS in second-line MCRPC remains, cabazitaxel and now abiraterone will help fulfill this need. The failure of Sutent means that abiraterone and cabazitaxel can exploit this underserved population, and the anticipated entry of Medivation/Astellas Pharma’s novel hormonal agent, MDV-3100, will also add to the therapeutic options in this setting.

The scale of abiraterone’s positive OS results is eagerly anticipated. With ESMO just a few weeks away we will see the clinical impact of abiraterone in MCRPC and also learn of other clinical results that will shape the future CaP market.
Posted on: 9/30/2010 3:33:28 PM | with 0 comments


Tags: Andrew Merron, Oncology

Trackback URL: http://decisionresources.com/trackback/2160fcec-e92c-4267-b7ba-063b558fa1dc/A-Turbulent-Time-in-Castrate-Resistant-Prostate-Cancer-–-Success-and-Failures-of-Late-Stage-Emerging.aspx?culture=en-US

Comments
Blog post currently doesn't have any comments.
Leave comment Subscribe



What is the abbreviation for Accountable Care Organization?

 

rss twitter linkedin

 

DRugwatch Blog

Quick insight on intriguing drug market developments from Decision Resources’ analysts.

Recent posts

Post title:
2015 ESC Congress in London – Overview of Upcoming Hot Line Sessions
Post date:
7/2/2015 11:57:46 PM
Post Summary:
Conor WalshContributor: Conor Walsh M.Sc., Ph.D.
Topics: Conference Commentary, Cardiovascular

This year’s ESC congress will take place in the Excel Exhibition Centre in London, United Kingdom. The spotlight this year is “environment and the heart,” highlighting the many different kinds of interactions between the environment and cardiovascular diseases.

Post title:
FDA Approval for The Medicines Company’s Intravenous Antiplatelet Kengreal
Post date:
6/23/2015 1:22:54 PM
Post Summary:
Conor WalshContributors: Conor Walsh, M.Sc., Ph.D.
Topics: Cardiovascular

On June 22nd, 2015 the U.S. FDA approved Kengreal (cangrelor), the Medicines Company’s intravenous antiplatelet drug for use “as an adjunct to percutaneous coronary intervention (PCI) for reducing the risk of periprocedural myocardial infarction, repeat coronary revascularization, and stent thrombosis in patients in who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor.”

Post title:
Hematological Malignancies: Are Immune Checkpoint Inhibitors Checking-in?
Post date:
6/17/2015 9:32:42 AM
Post Summary:
Contributor: Dana Gheorghe, Ph.D
Topics
: Conference Commentary, Oncology


Recent years have seen an added emphasis on the relationship between cancer and the activity of the immune system. Novel agents that aim to harness the immune system have already been approved in the U.S. for solid tumors (Bristol-Myers Squibb/Ono Pharmaceutical’s Opdivo [nivolumab] for NSCLC and malignant melanoma, and Merck & Co.’s Keytruda [pembrolizumab] for malignant melanoma), and are in development for a plethora of other oncology indications. Most of the development has been targeted towards solid tumors, but the potential of immune checkpoint inhibitors in hematological malignancies is becoming increasingly evident.

Post title:
Cardiovascular Outcomes Trials Answer Long-Asked Questions – But New Questions Arise
Post date:
6/12/2015 10:26:05 AM
Post Summary:
Contributor: Eamonn O'Connor, Ph.D.

The recent American Diabetes Association’s 75th Scientific Sessions in Boston saw the release of data from the ELIXA cardiovascular outcomes trial (CVOT) for lixisenatide (Sanofi/Zealand Pharma’s Lyxumia), the first such trial completed for the GLP-1 receptor agonist drug class. However, it was the publication of the data from the CVOT for sitagliptin (Merck’s Januvia/Ono’s Glactiv), known as TECOS1, that was most eagerly anticipated; this is because the previous CVOTs for saxagliptin (AstraZeneca’s Onglyza) and alogliptin (Takeda/Furiex’s Nesina/Vipidia) had raised significant concerns about a potential risk for increased rates of hospitalization due to heart failure. The results from TECOS therefore, were viewed as pivotal as to whether this risk was a feature specific to the DPP-IV inhibitor drug class.

Post title:
Malignant Melanoma: Evolving Standards of Care
Post date:
6/5/2015 2:52:20 PM
Post Summary:
Contributor: Natalia Reoutova, M.Sc.
Topics: Conference Commentary, Oncology

The past five years have seen unprecedented progress in the treatment of malignant melanoma, which translated into approval of highly efficacious immunotherapies, targeted small-molecule therapies, and several combination regimens.

Decision Resources Group brands include: