Urology | Biotech Strategy Blog

Insights from Society for Translational Oncology Prostate Cancer Symposium

By Pieter Droppert on October 31, 2011

The Oncologist Journal of the Society for Translational Oncology (STO) has published a video recording on prostate cancer that is well worth watching for those with an interest in this area.

At their Sept 8, 2011 CME symposium held in Belfast, a roundtable was held entitled “Prostate Cancer: Progress & Promise.”

Moderated by Bruce A. Chabner (Mass General/Harvard), the panelists were Joe O’Sullivan (Queen’s University, Belfast), Johann De Bono (The Institute for Cancer Research) and David Waugh (Queen’s University, Belfast).

Professor de Bono in the video comments that”

“with regards to our dream of eventually treating men with prostate cancer without castrating them, which must be our ultimate goal and curing them of cancer. I think we will have to focus on for example drugs targeting ERG or ERG signaling.”

Chabner then asks the good question of whether ERG is a druggable target?

To which De Bono replies that you can drug ERG by inhibiting PARP and references a paper by the Chinnaiyan group published in the May 2011 issue of Cancer Cell.

PARP inhibition represents an interesting area of prostate cancer research.

If you would like to know more, Sally Church, PhD has written about this on Pharma Strategy Blog. See posts on “TMPRSS2: ERG may be a more useful marker than PSA in prostate cancer” and “Personalized Therapy for Prostate Cancer – is it possible?”

In the STO video, De Bono discusses why he would like to replace bone scans in prostate cancer with another imaging modality that more accurately reflects the activity of the disease. Future possibilities include use of diffusion weighted magnetic resonance imaging and novel PET tracers.

There’s also a good discussion about Alpharadin for those interested in some anecdotal commentary on experiences with it.

Another notable comment by De Bono is his belief that “taxanes work in prostate cancer primarily by targeting androgen receptor signaling.” Taxanes have typically been thought to target mitosis.

De Bono goes on to say that clinical trial data being submitted for publication shows that patients who are refractory to abiraterone, are also refractory to docetaxel when they progress on it. The suggestion is that there may be cross resistance between abiraterone and taxanes with a subgroup of patients who just don’t do well on androgen receptor (AR) targeting drugs. The reason for this isn’t yet clear.

A new phase 2 clinical trial is starting soon that will look at the sequencing of abiraterone and cabazitaxel. One group will receive abiraterone followed by cabazitaxel, the other cabazitaxel followed by abiraterone.

The Belfast STO symposium was the second in a three part series. The next one will be held during ASCO GU in San Francisco next year.

Another potentially useful meeting in this area is the February 2012 AACR workshop on “Advances in Prostate Cancer Research” chaired by Arul Chinnaiyan & Charles Sawyers.

Prostate cancer remains an exciting therapeutic area to watch with tremendous progress and promise of late.

A year in review on Biotech Strategy Blog

By Pieter Droppert on October 26, 2011

Biotech Strategy Blog is 1 today! I can’t believe that a year has gone by so quickly! Before moving on to year 2, I thought a brief review might be interesting.

What have been the top posts on Biotech Strategy Blog this past year?

In terms of total visitors per post:

For those who like metrics:

Highest number of reads per month was in May (19,927)
Year to date there have been 79,179 visitors
Most visited day was September 22, 2011 (2136 reads)

What have been some of the other posts that I enjoyed writing about?

My top 5 (not in rank order) would be:

Finally, I have produced 4 videos that you can watch on the biotechstrategy channel on YouTube.

http://youtu.be/nDvY7opm3Fs

http://youtu.be/_oAJ1fU0PT4

http://youtu.be/hM_wmjaqDyc

http://youtu.be/i5GNBmuISqQ
It’s been a busy but enjoyable year. Biotech Strategy Blog is still a work in progress. If you have enjoyed a particular series of posts or would like me explore a topic or theme in the future, do email me or post a comment.

Vitamin E supplements lead to 17% increase in Prostate Cancer

Despite promising preclinical data suggesting that selenium and vitamin E may reduce prostate cancer risk, a randomized trial started in 2001 with over 35,000 men now suggests otherwise.

Given the prevalence of people taking vitamin supplements, these findings have important public health implications.

The results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) reported in the October 12, 2011 issue of the Journal of the American Medical Association (JAMA) show that dietary supplementation with Vitamin E significantly increased the risk of prostate cancer in healthy men.

Over 35,000 men were randomized into 4 groups: selenium (200 mg/d from L-selenomethionine) with matching placebo, vitamin E (400IU/d of all rac-a-tocopherol acetate) with matching placebo, both agents, or placebo. The study was stopped in September 2008 as a result of an interim analysis that showed lack of efficacy for risk reduction and futility analysis showed a lack of future benefit.

The data in 2008 with a median follow-up of 5.5 years suggested an increased risk of prostate cancer observed with vitamin E. That finding has now reached statistical significance in the latest analysis of the trial data, 7 years after the last patient was randomized.

Participants were healthy men at average risk of prostate cancer. They were monitored every 6 months and recommended to undergo prostate-specific antigen (PSA) and digital rectal examination (DRE) based on the standard of care in their community. The primary end point was prostate cancer incidence resulting from routine community care.

The updated results from the SELECT trial are published in JAMA by lead author Eric Klein from the Cleveland Clinic and colleagues. The data shows that the incidence of prostate cancer was greater in all treatment groups compared to placebo, but statistically significant only in the vitamin E group alone (P=0.008, HR: 1.17; 99% CI, 1.004-1.36).

The authors note this data means:

“The risk of prostate cancer at 7 years of median follow-up was increased by 17% in men randomized to supplementation with vitamin E alone, a difference that started to appear about 3 years after randomization.”

Why does Vitamin E supplementation cause this increased risk? The authors in their JAMA paper make no suggestion.

The data from this trial has important implications for all men who take multivitamin supplements. The authors note that more than 50% of all individuals over 60 take a vitamin supplement and 23% of them take a 400 IU/d or greater dose of Vitamin E, a dose that now has been shown to increase the risk of prostate cancer.

All too often we associate taking vitamins as healthy living. The conclusion of the authors is one that we should all take note of:

“The observed 17% increase in prostate cancer incidence demonstrates the potential for seemingly innocuous yet biologically active substances such as vitamins to cause harm.”

Only by doing clinical trials such as SELECT, can we assess the true harms and benefits of unregulated over-the-counter products such as vitamins.

Eric A. Klein, MD, Ian M. Thompson Jr, MD, Catherine M. Tangen, DrPH, John J. Crowley, PhD, M. Scott Lucia, MD, Phyllis J. Goodman, MS, Lori M. Minasian, MD, Leslie G. Ford, MD, Howard L. Parnes, MD, J. Michael Gaziano, MD, MPH, Daniel D. Karp, MD, Michael M. Lieber, MD, Philip J. Walther, MD, PhD, Laurence Klotz, MD, J. Kellogg Parsons, MD, MHS, Joseph L. Chin, MD, Amy K. Darke, MS, Scott M. Lippman, MD, Gary E. Goodman, MD, Frank L. Meyskens Jr, MD, & Laurence H. Baker, DO (2011). Vitamin E and the Risk of Prostate Cancer, The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA: The Journal of the American Medical Association, 306 (14), 1549-1556

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Prostate Cancer Screening – the debate continues

The recent announcement from the United States Preventative Services Task Force (USPSTF) on prostate cancer screening has stimulated a lot of debate. “Dr Len’s Cancer Blog” from the American Cancer Society has a thoughtful piece about the “to screen or not to screen” dilemma. It is reminiscent of the breast cancer mammography debate.

Scott Hensley’s post on “Shots”, the NPR health blog also provides a good overview of the debate and issues. I confess I was surprised by the vehemence of the response from some practising urologists on twitter such as Dr Benjamin J. Davies (@daviesbj), Assistant Professor of Urology at the University of Pittsburgh School of Medicine:

What do the US Preventative Task Force authors say? In the findings published in the October 7, 2011 issue of the Annals of Internal Medicine, the conclusion from their peer-review of the literature is that:

“screening based on PSA identifies additional prostate cancers, but most trials found no statistically significant effect on prostate cancer–specific mortality.”

This is nothing new – the evidence in favor of Prostate-Specific Antigen (PSA) screening for prostate cancer has for sometime been inconclusive at best. Research published in the British Medical Journal earlier this year suggested that indiscriminate screening for prostate cancer may not be of value until we obtain more sensitive biomarkers.

All the USPSTF have done is a retrospective literature review that confirms our current state of knowledge.

Despite the amount of $$$ that have been spent on PSA clinical studies, no convincing data in support of it as a screening tool for all men has been developed. That’s not to say that it has no utility or benefit.

If PSA screening does detect some prostate cancers and early treatment may save lives particularly in those with an aggressive form of the disease, then it’s hard not ask:

What is the alternative if PSA screening is now discouraged?
Will this mean more men will not be screened, even those at high risk, with a consequent increase in prostate cancer mortality or lower overall survival?
Will insurers refuse to cover PSA testing moving forwards?
Will family physicians actively discourage PSA testing?

One limitation of the USPSTF report that struck me while reading through the analysis and recommendations, was the absence of data from the Prostate Cancer Intervention versus Observation (PIVOT) trial that was presented in the plenary session at the American Urological Association (AUA) annual meeting earlier this year.

I wrote in a previous blog post about the PIVOT data presented at AUA 2011 by Dr Wilt. This VA/NCI/AHRQ randomized clinical trial showed in a 12 year follow-up of over 5000 men with localized prostate cancer, no benefit from radical prostatectomy in low risk early stage patients.

In my opinion it is practice changing data that sadly has not yet been published in a peer-reviewed journal which is why it was not included in the USPSTF analysis. A few photographs that I took at the presentation of the PIVOT data are shown below:

The 12 year survival data showed that in those patients with PSA <=10 ng/ml there was no significant difference in survival over observation versus RP.

However in those patients with PSA > 10ng/ml there was a significant difference in mortality (p=0.03 HR=0.36) suggesting that in the small sub-group of patients with high PSA, RP did provide a benefit over “watchful waiting.” PSA measurements may therefore help in the treatment and ongoing management of patients.

If one of the challenges of PSA screening is the issue of the harms from treatment, then the PIVOT data that showed no difference in mortality through watchful waiting over radical prostatectomy (RP) except for high risk patients is important.

Roger Chou and his colleagues in their Annals paper did note this:

“When available, results from the Prostate Cancer Intervention Versus Observation Trial, which compared prostatectomy with watchful waiting for screening-detected cancer, may help clarify which patients would benefit from prostatectomy or other active treatments, potentially reducing harms from unnecessary treatment.”

The issue may, therefore, not be one that PSA screening per-se is the problem, but that in too many men, a raised PSA results in unnecessary surgery or overtreatment with its consequent risks and harms.

As reported by Alemozaffar and colleagues in the September 21, 2011 issue of the Journal of the American Medical Association (JAMA), 2 years after RP only 35% of men could maintain a functional erection.

“At 2 years after treatment, erectile dysfunction was reported by 619 of 987 (63% [95% CI, 60%-66%]) men (334/511 [65% {95% CI, 61%- 69%}] in the prostatectomy group”

That’s depressing news when coupled with other side-effects from RP or other interventions such as incontinence or problems with bowel function.

It adds further support to the idea that the potential risks versus benefits from prostate cancer surgery and deciding who should actually have surgery or other intervention, is where there’s also a need for more debate.

Men need to be able to make an informed decision. Some urologists may not be unbiased in their treatment recommendations given they have a vested interest in earning money from surgery or maintaining utilization rates of expensive robotics. Data from the PIVOT trial, when published, is evidence-based medicine that will impact their practice.

Use of prostate cancer risk calculators to assess those patients at high risk who might benefit from RP or other intervention could also help lower the harms that currently impact the utility of PSA screening.

How will men approach the PSA screening debate? Despite the USPSTF recommendations I will still be asking my physician for an annual PSA test, so long as it remains covered by my health insurance. The PSA test and digital rectal exam remain the main ways we have to detect prostate cancer early.

Psychologically I value the risk of picking up a disease early higher than the downside of a false positive. I would, however, not rush into any surgery or radiotherapy absent a clear finding that the benefits of intervention outweighed the potential harm.

My approach towards prostate cancer PSA screening again reminds me of the debate over mammography. We all want to discover cancer early, and have the best possible treatment options as a result.

Hopefully, as our understanding of the biology of prostate cancers and associated biomarkers develop we may be able to generate new screening tests that have fewer false positives than PSA and provide for more accurate early diagnosis.

Alemozaffar, M., Regan, M., Cooperberg, M., Wei, J., Michalski, J., Sandler, H., Hembroff, L., Sadetsky, N., Saigal, C., Litwin, M., Klein, E., Kibel, A., Hamstra, D., Pisters, L., Kuban, D., Kaplan, I., Wood, D., Ciezki, J., Dunn, R., Carroll, P., & Sanda, M. (2011). Prediction of Erectile Function Following Treatment for Prostate Cancer JAMA: The Journal of the American Medical Association, 306 (11), 1205-1214 DOI: 10.1001/jama.2011.1333

Roger Chou, MD, Jennifer M. Croswell, MD, MPH, Tracy Dana, MLS, Christina Bougatsos, BS, Ian Blazina, MPH, Rongwei Fu, PhD, Ken Gleitsmann, MD, MPH, Helen C. Koenig, MD, MPH, Clarence Lam, MD, MPH, Ashley Maltz, MD, MPH, J. Bruin Rugge, MD, MPH, & Kenneth Lin, MD (2011). Screening for Prostate Cancer: A Review of the Evidence for the U.S. Preventive Services Task Force Annals of Internal Medicine, E-375 (October 7)

Alpharadin wlll be new treatment option for Prostate Cancer

One piece of hot news at the 2011 European Multidisciplinary Cancer Congress (twitter #EMCC2011) taking place in Stockholm this weekend is the data on radium-223 chloride (Alpharadin) in metastatic castration resistant prostate cancer. The phase 3 ALSYMPCA trial results were presented in yesterday’s presidential symposia by Dr Chris Parker, Consultant Clinical Oncologist at The Royal Marsden Hospital.

The Scandinavian location for the presentation could not have been better, given that Alpharadin was developed by the Norwegian company Algeta. Bayer Schering Pharma AG have the worldwide commercial rights, but Algeta maintains a co-promotion option in the United States.

I first picked up on Alpharadin in a presentation given at the American Urological Association (AUA) annual meeting by Oliver Sartor (Tulane) earlier this year when he reviewed new prostate cancer products in development.

At the ASCO 2011 meeting in Chicago there was a poster on the Alpharadin Phase 2 trial data (see the figure on the right) that caught my attention given that it showed an overall survival (OS) advantage. This news was, however, largely drowned by the interest in cabozantinib (XL184).

The result is that Alpharadin has to many come out of left field. It is a promising compound for the treatment of prostate cancer that will provide new treatment options for patients with metastatic disease. In particular, use in combination with other therapies such as abiraterone acetate (Zytiga) may prolong survival to a greater extent than either does individually.

Currently, radium-223 chloride (Alpharadin) is only in investigational use and is not approved in Europe or the United States. It is, however, on the fast track towards FDA approval in 2012.

What makes Alpharadin exciting as a new treatment option for castration resistant prostate cancer (CRPC) is that the ALSYMPCA trial data shows that it not only provides a significant median overall survival (OS) benefit of 2.8 months compared to placebo (14 months versus 11.2 months, p=0.00185, HR 0.695), but significantly delays the time to first skeletal event by 5.2 months (13.6 months versus 8.4 months, p=0.00046, HR 0.610).

The overal survival (OS) benefit seen in the ALYSMPCA phase 3 trial is comparable to other approved agents in the post-docetaxel setting for CRPC. However, where it is unique is in the additional effect it has on skeletal related events (SRE), a common occurrence in metastatic prostate cancer. Bone metastases are painful and have a significant impact on quality of life.

Other compounds that target the bone microenviroment such as denosumab (Xgeva), provide a delay in the time to first skeletal event in prostate cancer patients but to-date have not been shown to confer an overall survival advantage. This means that Alphardin is the first bone targeted agent to confer both an overall survival and a delay in time to first skeletal event.

After Dr Parker’s presentation of the ALSYMPCA phase 3 trial data yesterday here in Stockholm, Professor Wim Oyen of the Department of Nuclear Medicine in Nijmegen discussed the data.

What he noted was the high tolerability of Ra-223 chloride (Alpharadin) as compared to other radiopharmaceuticals for treatment of patients with bone metastases. He discussed how the emission of alpha particles allows for a short range effect (a few cell diameters) that is very localized, but with a large biological effect.

Oyen highlighted the “opportunity for improving patient outcome by adding Ra-223 in regimens of combination therapy,” something that Dr Parker speculated about in his media briefing.

Professor Oyen also saw “an opportunity for improving patient outcome by using Ra-223 in an adjuvant setting.” His conclusion based on the phase 3 ALSYMPCA trial data presented was that radium-223 chloride (Alpharadin) is an “effective, very well tolerated and convenient treatment modality.”

Dr Parker mentioned to me, while waiting for a train back to Stockholm, that the ALSYMPCA trial data he presented had not yet been submitted for publication. He said he would be disappointed if it did not appear in the New England Journal of Medicine. Given that it is groundbreaking and “practice changing,” I would be surprised if it is not published in the NEJM in due course.

I am sure that we will be hearing more about radium-223 chloride (Alpharadin) in the forthcoming months, especially now it is on fast track to FDA approval in 2012.

Although not a cure for prostate cancer, the ALSYMPCA trial data presented here in Stockholm is further good news for patients, and will provide a potential new treatment option for urologists and oncologists.

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Alpharadin Prostate Cancer data will be “Practice Changing” #EMCC2011

Radium-223 (Alpharadin) will be “Practice Changing” is how Michael Baumann, President of the European CanCer Organisation (ECCO) and Jean-Charles Soria, Co-Scientific chair of the 2011 Stockholm Multidisciplinary Cancer Congress described the prostate cancer clinical trial data to be presented in the Presidential (plenary) session on Saturday September 24, 2011.

Alpharadin is the first bone targeted therapy to show an overall survival (OS) advantage in metastatic castration-resistant prostate cancer (mCRPC). To date, none of the other therapies targeting bone in prostate cancer such as zoledronic acid (Zometa), denosumab (Xgeva) or cabozantinib (XL184) have shown any overall survival benefit.

The Alphardin data from the phase 3 ALSYMPCA trial that will be presented in Stockholm shows an increase in overall survival of 2.8 months compared to placebo (median OS of 14 months with Alpharadin versus median OS of 11.2 months with placebo, p=0.00185, HR=0.695).

What is big news is that Alpharadin also significantly prolongs time to first skeletal related event (p=0.00046; HR=0.610). This is tremendous news for prostate cancer patients given the number that experience bone metastases.

It is not, however, good news for Amgen and denosumab (Xgeva). Amgen have tried to associate the improvement in symptoms and decline in skeletal related events with survival, but have failed to obtain any overall survival data (OS). This is something that Alphardin achieves as well as a significant reduction in time to first skeletal related event (SRE).

What Alpharadin has effectively shown is that by nuking bone metastases using a weak alpha emitting radium-223, overall survival (OS) can be prolonged in a way that targeting rank ligand does not. This is ground breaking news and the 2011 Stockholm Multidisciplinary Congress have rightly recognized the importance of this data with a plenary session. For further information on how Alpharadin works – see my previous blog post about the ASCO 2011 phase 2 data.

At the press briefing late friday afternoon in Stockholm, Dr Chris Parker of the Royal Marsden Hospital and PI of the ALSYMPCA study said that “Radium-223, a novel alpha-pharmaceutical, may provide a new standard of care for the treatment of CRPC patients with bone metastases.”

There is no doubt in my mind that it will lead to a new standard of care. What’s more as Dr Parker speculated in the press briefing, there is no reason why Alphardin could not be combined with androgen receptor antagonists such as the recently approved abiraterone acetate (Zytiga).

Both are well tolerated and operate by different mechanisms of action. It’s hard not to believe that the overall survival of CRPC patients will be increased by such a combination.

When approved, Alpharadin and any possible combination with Zytiga, may further delay the use of sanofi-aventis’ cabazitaxel (Jevtana) in the post-doctaxel CRPC setting. It may also potentially have an impact on the use of sipuleucel-T (Provenge) in the asymptomatic population.

The Alpharadin phase 3 trial results is exciting news from the 2011 Stockholm Multidisciplinary Cancer Congress. I will be writing more after Dr Parker presents the data in the Presidential session later today.

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Alpharadin on fast track to FDA prostate cancer approval in 2012

Earlier this week Bayer & Algeta announced that Alpharadin™ (radium-223 chloride) had received Fast Track designation from the FDA for the treatment of castration-resistant prostate cancer (CRPC).

Bayer signed an agreement with Norwegian based Algeta in 2009 for the global commercial rights to Alpharadin™, with Algeta retaining a 50/50 co-promotion and profit-sharing in the United States.

According to the Algeta August 23, 2011 press release, in light of the FDA fast track designation they plan on filing for United States approval in mid-2012, ahead of previous expectations.

At the ASCO annual meeting in Chicago this year, phase II clinical trial data for Alpharadin™ was presented during the poster session (Abstract #4620). You can obtain a copy of the poster here.

ASCO Alpharadin™ Phase 2 Data showed increase in Overall Survival

What impressed me when I saw the poster and talked to Gillies O’Brien-Tear, the Chief Medical Officer for Algeta, was the increase in overall survival (OS) seen. In the phase 2 study presented, Alpharadin™ improved OS by 4.5 months versus placebo when added to the standard of care in patients with CRPC and bone metastases.

To me this stands out from other drugs that are targeting bone metastases in CRPC, such as cabozantinib (XL184) and denosumab (Xgeva®), where to my knowledge no overall survival benefits have yet been seen.

Despite the lack of OS benefit, Amgen announced earlier this week on Aug 22nd, they had made a supplemental BLA application for denosumab to expand the indication to include the prevention of bone metastases in CRPC. The PDUFA date is April 12, 2012.

Will Xgeva® and Alpharadin™ be viewed as potential competitors or used synergistically? It will be interesting to see any data that shows the impact of Alpharadin™ on bone pain and quality of life, and how physicians view the new treatment options that may be available to them.

How does Radium-223 chloride act?

It is a calcium mimetic that is taken up by bone, where the radium then emits alpha-particles that act on the prostate cancer bone metastases. The radiation is only short range (2-10 cell diameters) which limits its toxicity to healthy tissue and results in localized and focused radiation that kills metastatic cancer cells in the bone.

The day after the phase 2 results were presented at ASCO, Algeta and Bayer announced on June 6, positive data from the interim analysis of the phase 3 ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer patients) trial.

This study began in June 2008, with enrollment of 922 patients completed in January 2011. According to the June 6 press release, the interim analysis of the ALSYMPCA trial showed a statistically significant increase in overall survival in CRPC patients receiving Alpharadin™ compared to placebo.

Median overall survival was 14.0 months for Alpharadin™ and 11.2 months for placebo (two-sided p-value = 0.0022, HR = 0.699)

As a result of the interim analysis, the independent data monitoring committee recommended that the trial be stopped and patients on the placebo arm offered treatment with Alpharadin™. Dr Chris Parker, from the Royal Marsden Hospital, and Principal Investigator of ALSYMPCA, said:

“Based on the observed survival benefit and its safety profile, Alpharadin may become an important treatment for patients with bone metastases from advanced prostate cancer.”

At the forthcoming European Multidisciplinary Cancer Congress in Stockholm (co-sponsored by ECCO, ESMO and ESTRO), the phase III Alpharadin data for the ALSYMPCA trial will be presented as a late breaking abstract on September 24, 2011 in the Presidential Session.

The abstracts for the meeting are not yet available, but in the light of the FDA Fast Track designation earlier this week, and the fact the ALSYMPCA trial results will be presented in a plenary session at Stockholm, positive data is expected.

The prostate cancer market is certainly heating up with the approval earlier this year of Zytiga™ (abiraterone acetate) and several products in late stage development such as Alpharadin™, MDV3100, TAK-700 and custirsen (OGX-011). It’s good news for patients that new treatment options may be available before too long. As to how these new therapies are used, sequenced and combined, that is set to be the topic of conversation at medical and scientific meetings over the coming year.

Zytiga European Prostate Cancer approval may kill Jevtana sales

With the collapse of the Dendreon share price today following poor sales data (Adam Feuerstein on The Street has an excellent write up about this), attention has again focused on the prostate cancer market.

Zytiga (abiraterone acetate) was recently approved by the European Medicines Agency (EMA), following FDA approval earlier this year.

The EMA Committee for Medicinal Products for Human Use granted the marketing authorization for Zytiga at it’s July 2011 meeting. The approval noted,

“The poor prognosis of the target patient population represents a high unmet medical need while the novel mechanism of action of abiraterone has the potential to offer an alternative therapeutic option for these patients.”

What does this mean for sales of sanofi-aventis’ cabazitaxel (Jevtana), which was approved in Europe earlier this year?

Given that both drugs have approval in the same indication for metastatic castrate resistant prostate cancer (mCRPC) post-docetaxel chemotherapy, and the price is likely to be comparable, my guess would be that Jevtana sales will take a big hit.

After a sick prostate cancer patient has undertaken several cycles of chemotherapy with docetaxel, why would they not want to take an oral pill as opposed to another chemotherapy drug, which does have a less than stellar adverse-event profile. The answer is they will probably take a chemo-holiday and use Zytiga.

Jevtana simply came to the market too late in Europe, and Zytiga gained accelerated approval. It’s a reminder that we live in a dynamic pharmaceutical market place, as the news last night from Dendreon has also reminded us.

Prostate Cancer Market to expand from $1B to $5B by 2015

The market for prostate cancer therapies is set to expand from $1 billion currently to $5 billion by 2015, according to analysts reported by this morning’s Washington Post/Bloomberg news. This is perhaps no surprise given the recent approval of abiraterone acetate (Zytiga®) from Ortho Biotech (JNJ).

New clinical data on prostate cancer clinical trial results is expected at the 2011 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago this weekend from many of the prostate cancer therapies in development such as MDV3100, TAK700, ARN-509, cabozantinib (XL184), ipilimumab, custirsen (OGX-11), BPX-101, alpharadin, denosumab (Xgeva®) and Prostvac-VF.

Indeed, one could argue that prostate cancer is becoming a competitive marketplace. Any emerging biotechnology company that is not already developing a prostate cancer drug is likely to find it a hard market in which to create a blockbuster. By the time any drug comes to market, there will be incumbents with effective products who have captured market share.

Prostate cancer is an exciting market to watch from a marketing strategy and patient perspective, as several companies potentially bring new products to market over the next few years.

However, the bottom line is that patients will live longer as a result of all the innovation that is taking place. Not only that but physician education and awareness of how to treat this disease is also likely to improve as they seek out knowledge on new therapies and treatments. This to many will make a major difference. At the recent American Urological Association (AUA) annual meeting, the sessions on treatment of prostate cancer were standing room only. There is clearly a demand for knowledge out there as the treatment paradigms change.

At the other end of the spectrum, there is also innovation taking place in terms of improved diagnosis and treatment of prostate cancer. Whether we should screen all men for PSA remains a controversial topic, although use of risk calculators do appear to offer less false positives. Indeed, calculating risk is going to be one of the key areas that primary care physicians and urologists need to focus on, particularly in the light of the PIVOT trial data that was presented at AUA, showing radical prostatectomy (with risks including incontinence and erectile dysfunction) was not better than watchful waiting in low-risk, early stage disease.

However, a presentation I am looking forward to at ASCO 2011 is on circulating tumor cells (CTC) and whether these can be a prognostic or even a predictive biomarker. Both the phase III MDV3100 and abiraterone acetate clinical trials captured CTC data. It will be exciting news at ASCO 2011 if circulating tumor cells that require only a blood sample offer an improvement over PSA not only for detection of prostate cancer, but in monitoring the disease over time.

I will be at ASCO 2011 this weekend, and look forward to writing more on prostate cancer from the conference!

ASCO 2011 Cabozantinib (XL184) may be an exciting new prostate cancer drug

It’s hard to believe that the countdown to the 2011 annual meeting of the American Society of Clinical Oncology (ASCO) is now underway, but yesterday at 6pm, the ASCO abstracts were released.

Oliver Sartor at the recent annual meeting of the American Urological Association (AUA) highlighted the prostate cancer potential of cabozantinib (XL184), an oral inhibitor of MET and VEGF kinases, so it was interesting to see that new data will be presented at ASCO.

What makes cabozantinib interesting?

The preliminary data shows that it not only has an anti-tumor effect, but also has an effect on bone metabolism.

The data presented at EORTC last year and at ASCO GU this year confirms what was seen in animal models, in that it had both an anti-metastatic effect on soft tissue and blockade of bone lesions. Such dual action on both bone mets and the tumor microenvironment makes it an exciting new compound in prostate cancer.

By all accounts, the novel effect of cabozantinib on bone mets is unexpected.

At the forthcoming ASCO meeting, abstract 3010, whose lead author is Dr Michael Gordon of Pinnacle Oncology Hematology in Scottsdale, AZ will present data on:

“Activity of cabozantinib (XL184) in soft tissue and bone: Results of a phase II randomized discontinuation trial (RDT) in patients (pts) with advanced solid tumors.”

According to Dr Gordon in the ASCO press teleconference yesterday, the phase II data at ASCO for cabozantinib in prostate cancer will show:

Complete or partial bone scan resolution in majority of patients (86%), often accompanied by pain relief

Unprecedented bone scan improvement

On the basis of these promising results, according to Dr Gordon, “Exelixis plans to initiate the first pivotal trial in prostate cancer by the end of 2011.”

It will be interesting to see whether cabozantinib can impact overall survival (OS) in advanced prostate cancer, something that denosumab (Xgeva®) failed to show in the 147 trial that was just presented at AUA.

There are several abstracts on cabozantinib at the ASCO 2011 annual meeting. Another one that caught my attention was abstract 4516, whose lead author is Maha Hussein of the University of Michigan.

Dr Hussein will present data on cabozantinib in metastatic castrate resistant prostate cancer (mCRPC). The abstract’s conclusion is that:

Cabo showed clinical activity regardless of prior D in mCPRC pts, particularly in pts with bone disease, as reflected by high rates of b-scan resolution and pain relief, in addition to improvements in Hb and tumor regression.

I’ll be at ASCO in a few weeks time, so look forward to hearing more detail on the cabozantinib results. The data is still very preliminary, but cabozantinib (XL184) is certainly a drug to watch, and may be an exciting new prostate cancer drug in the future.

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