Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘ESMO 2011’

San Antonio – there is a lot of exciting new data at the San Antonio Breast Cancer Symposium (SABCS) this week.

As Sally Church pointed out in her SABCS video on Pharma Strategy Blog, the update to the BOLERO2 data  (previously presented by Jose Baselga at ECCO/ESMO 2011 in September) will be presented later this morning at SABCS.

As a side note it is worth noting that the NEJM paper published yesterday contains the Stockholm data, not the updated data that will be presented later today that will show further improvement in progression free survival (as compared to placebo) in post menopausal ER+ HER2- women who took everolimus combined with exemestane.

Despite the presentation of exciting data at SABCS this week, my opinion is that this is a good meeting, but not a great one (yet). The reason is not the quality of the science being presented this week, but the lack of quality discussants.

The unheralded discussant is the expert that puts the science in context for the audience. Whether it’s a discussion of a simple poster or of a plenary session, the discussants play an important role.

Yesterday at SABCS I sat through two general sessions (the equivalent of plenary sessions at other meetings) in the cavern like auditorium that I estimate sits two thousand attendees.

Of the 15 presentations, only the 3 on bisphosphonates were given a discussant. That is why this meeting to me is good, but not great.  Both ASCO and ESMO/ECCO do a much better job at having a expert put the data in context in an independent and unbiased review.

Why is a discussant important when it’s all about the scientific data?

The challenge with medicine, law and any other professions is that there is so much new data that we can only be experts in a very small area or subset of knowledge.

At SABCS there are basic scientists, medical students, researchers, oncologists, community physicians, patient advocates and survivors. What does the data presented mean to them?

The discussant looks at many aspects of a presentation and can be critical, positive and negative in their observations about:

  • Clinical Trial Design:  what were the limitations?
  • Results:  did it meet the endpoints, was the data significant?
  • Adverse events: is the AE profile a concern?
  • Comparison to literature:  how does this data compare to the literature?
  • Future research:  does this data suggest rational future trials or research?
  • Practice implications:  does the data impact the standard of care?

There are many more questions that come to mind.  Listening to a good discussant brings science to life.

It is, however, challenging being a discussant because like writing a blog, you are generating original content and expressing an opinion.

My view is that if a presentation is good enough to receive an oral presentation at a major meeting, then it’s good enough to be discussed.  I hope that SABCS will offer more discussants in future years and make this a great scientific meeting in return.

The patient advocacy session on “Cancer and the Internet” at the 2011 European Multidisciplinary cancer congress (#EMCC2011) in Stockholm was well attended by patient advocates from across Europe, as well as industry and communications professionals.

The session focused on building online communities, how the internet can help patients with rare diseases have a voice with policy makers and showcased the new European cancer portal: ecancerHub.

Chaired by CML advocate, Jan Geissler (@jangeissler) the session heard from ACOR founder Gilles Frydman (@gfry), Denis Costello from Eurodis (@rarecare) and Richard Sullivan from Kings College London.

Earlier this year, the PEW Internet & American Life Project reported that 80% of internet users have looked for online health information around a disease or major health topic. The internet continues to grow in its importance to patients and how the pharmaceutical/biotechnology industry reaches them.

One of the challenges expressed in questions from the audience was the plethora of information available on the internet to patients, and how the number of available sites continues to grow, leading to overwhelm.  Knowledge, as Gilles Frydman wryly observed, is always in beta.

ecancerHub is a new online global cancer community and knowledge portal

Superportals such as the ecancerHub are likely to play an increasing role in how patients share information and research the internet, especially if they can curate reliable, accurate and independent sources of information.

Funded by the European Commission’s eurocancercoms project, ecancerHub aims to become a leading knowledge base for cancer information and also where online communities of patients can easily meet to share experiences and learn from each other.

Other than a quick visit, I have not yet had the chance to check the site out fully, but it looks promising. I was particularly interested by the future developments that were discussed, such as focused search engines that will help people find clinical trial or cancer information.

Ultimately, ecancerHub will only succeed if it gains a critical mass of users and to do this, not only must it become widely known, but it also has to offer superior content, ease of use and an online experience that promotes patients to preferentially build enduring and valuable communities on it as a one stop hub, rather than elsewhere.

If you are a cancer patient or have an interest in healthcare social media, ecancerHub is worth a visit.

The phase 3 ALSYMPCA prostate cancer trial results for radium-223 chloride (Alpharadin) were presented at the recent ECCO ESMO ESTRO 2011 European Multidisciplinary Cancer Congress in Stockholm. This was the highlight of the meeting for me.

There was also exciting data in Breast Cancer (BOLERO-2) that you can read more about on Pharma Strategy Blog.

Alpharadin from Norwegian company, Algeta, is the first new treatment for advanced prostate cancer that not only prolongs overall survival (OS) but delays time to first skeletal related event (SRE) in metastatic castration resistant prostate cancer patients.

Leading physicians at the meeting believe that it will be “practice changing.

The Alpharadin data may also have an impact on other bone targeted agents in development for prostate cancer such as cabozantinib (XL184).

Sally Church, PhD (who writes the Pharma Strategy Blog) is quoted by “The Street” as saying that “Alpharadin raises the bar for Exelixis. They have to produce overall survival data now.” Overall Survival (OS) remains the primary regulatory endpoint in prostate cancer drug development.

Prostate cancer experts Johann de Bono and Cora Sternberg also mentioned, in presentations at the Stockholm meeting, that in the future it will be increasingly difficult to do placebo controlled trials in Prostate Cancer given the new treatment options available.

Alpharadin is not yet approved in Europe or the USA, but is on fast track for approval by the FDA in 2012.

Chris Parker (Royal Marsden Hospital) presented the Alpharadin ALSYMPCA trial data as a late breaking abstract in the presidential session at ECCO ESMO 2011. He also conducted a media briefing that I was fortunate to video.

You can watch this below. In it he explains how radium-223 choloride works and why he (and others) believe this may change the standard of care for prostate cancer patients with bone metastases. It is well worth watching!


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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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I will be flying to Stockholm next week for the European Multidisciplinary Cancer Congress (twitter #EMCC2011), more commonly known as ECCO or ESMO 2011.

What are the sessions that look interesting at the meeting? I previously wrote about the phase III ALSYMPCA trial data for Alpharadin that will be presented as a late breaking abstract.

In addition, the best abstract at ECCO 2011 is on vismodegib in basal cell carcinoma.  Sally Church on Pharma Strategy Blog has written extensively about the hedgehog pathway and role of smoothend inhibition in the treatment of cancer.

What else has attracted my attention at ECCO 2011 in Stockholm? In looking at the preliminary program I was struck by the large number of scientific symposia throughout the meeting. However, many occur at the same time! On Saturday 24th two in particular caught my attention:

Molecular Imaging of Hypoxia

Nanotechnologies for Targeted Drug Delivery

Having written about hypoxia and nanotechnology on this blog, I will probably go to one of those two sessions.

Later in the conference, there is another block of scientific symposia on Monday 26th, again all at the same time! Several that look particularly interesting include:

  • How to understand and to Reverse Drug Resistance in Metastatic Breast Cancer
  • From New Targets to New Drugs in Prostate Cancer
  • Tailoring Personalized Medicine for the Future
  • The Role of IGFs/IGF-1R Pathway in Paediatric Malignancies

And in case one still hasn’t had enough science, there’s another group of scientific symposia on the final day of the conference on Tuesday, 27 September including:

  • Unravelling Ras PI3 Kinases Targets 
  • PARP inhibiting strategies: from Molecular Mechanisms to Rational Clinical Applications

I expect Stockholm to be expensive, they jokingly say you can buy a brewery in America for the price of a beer in the city, but it looks like there’ll be some interesting news and scientific data from the meeting. Hopefully I’ll have a few hours sometime to see something of what looks like a stunningly beautiful city.

If you plan to be in Stockholm do let me know. I can be reached via twitter (@3NT).

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.

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