Biotech Strategy Blog

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

Posts tagged ‘Radium 223 Prostate Cancer’

It’s now time to turn our attention to genitourinary oncology and, in particular, prostate, renal and urothelial bladder cancers. This week brings this ASCO GU meeting (#GU15), which is being held in Orlando this year and began this morning.

There are quite a few interesting topics being covered here, particularly in the poster sessions over the next three days. Hopefully, 2015 will also bring more good news in this space as 2014 was a rather dismal one on several fronts!

We decided to highlight some of the most interesting abstracts on castrate resistant prostate cancer and urothelial bladder cancer in our latest conference preview.

To learn more about the hot topics in GU cancer, interested subscribers can sign in or sign up below.

The abstracts for the forthcoming American Society of Clinical Oncology 2012 Genitourinary Cancers Symposium (ASCO GU) have been released and offer insight into some of the new data that will be presented at the meeting.

radium-223 Alpharadin Prostate CancerThe results of the phase III ALSYMPCA trial for radium-223 (Alpharadin) in prostate cancer were presented at ECCO/ESMO last September by Dr Chris Parker.

As expected, there is no change to data presented in Stockholm that showed radium-223 (Alpharadin) improves both Overall Survival and Skeletal Related Events:

radium-223 Overall Survival Benefit
median 14.0 vs 11.2 months; P value = 0.00185; HR = 0.695

radium-223 time to first SRE 
median 13.6 vs 8.4 months; P value = 0.00046; HR = 0.610

However, the meeting abstract published today shows that radium-223 in bone-metastatic castration resistant prostate cancer patients (CRPC), not only significantly prolonged time to first skeletal related event (SRE), but significantly prolonged 3 out of the 4 SRE components:

  • time to spinal cord compression,
  • time to pathological bone fracture
  • time to external beam radiation

No significant improvement in the SRE component of time to surgical intervention was seen with radium-223.

Subscribers to Premium Content can login to read commentary by Dr Oliver Sartor on the clinical significance of this data:

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Times-Square-NYC-November-11-2011This morning the 8am session at the Chemotherapy Foundation Symposium (The Greenspan Meeting) in NYC featured a review of current developments in Prostate Cancer.

The informative 1.5 hour session covered a lot of ground with the presenters reviewing clinical data for:

  • Radium-223 Chloride: a new option for CRPC (Oliver Sartor)
  • Pomegranite extract for Rising PSA (Michael Carducci)
  • XL184 in mCRPC (David Smith)
  • Optimizing patient selection for sipuleucel-T (Simon Hall)
  • Intermittent androgen suppression for prostate cancer (Laurence Klotz)
  • Lenolidomide/docetaxel in CRPC (Daniel Petrylak)

Oliver-Sartor-MD-presenting-at-NYC-Chemotherapy-Foundation-Symposium-2011The highlight, in my opinion, was Oliver Sartor’s excellent presentation on radium-223 chloride (Alpharadin) in which he cogently outlined its mechanism of action.  He explained that radium-223:

  • targets osteoblastic bone metastases by acting as a calcium mimic
  • is a bone-seeking calcium mimetic that binds to hydroxyapatite
  • has preferential uptake in areas of new bone formation

As mentioned previously on this blog, there are critical differences between an alpha emitter such as radium-223 and other bone-seeking radiopharmaceuticals that are beta emitters.

Sartor presented some excellent slides that showed how alpha emitters require much fewer DNA hits to kill cells, are short range and have a higher initial energy per particle.  In other words they are very effective at short range within the bone microenvironment, something that Chris Parker from The Royal Marsden Hospital mentioned in his interview from ECCO/ESMO in Stockholm.

Sartor concluded his Chemotherapy Foundation Symposium presentation by reflecting on “where do we go from here” in prostate cancer?  Some of his observations were:

  • We are currently in a sequencing paradigm. Drug A then B then C
  • We need to combine active agents to give the best results, that is our next challenge
  • How are we going to afford it all?

Sartor succinctly highlighted where the rubber currently hits the road, and left the audience with plenty to reflect upon. I am sure we can expect further debate on sequencing and combination possibilities at medical and scientific meetings in 2012.

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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:

  1. Results from NEJM Lucentis v Avastin AMD CATT clinical trial
  2. AUA Results from PIVOT study show no benefit from radical prostatectomy in low risk early stage patients
  3. ASCO 2011 Cabozantinib (XL184) may be an exciting new prostate cancer drug
  4. Merck’s capthepsin-K inhibitor odanacatib in osteoporosis
  5. Update from AACR on new prostate cancer drugs to watch

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:

  1. Alpharadin will be new treatment option for prostate cancer
  2. Patient advocacy session at European Hematology Assocation EHA Congress shows impact of drug adherence on outcome
  3. How nanotechnology may revolutionize the detection of traumatic brain injury using a sensor that changes color
  4. Innovation in Nanotechnology will lead to improved drug delivery, diagnostics & imaging
  5. Insights of the decade

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


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.

Radium-223 (Alpharadin) is a novel bone targeted treatment for advanced prostate cancer.

At the recent European Multidisciplinary Cancer Congress in Stockholm (EMCC 2011), Dr Chris Parker from The Royal Marsden Hospital presented results of the phase 3 ALSYMPCA trial that showed both delayed time to first skeletal-related event (SRE) AND an overall survival (OS) benefit for those men with advanced prostate cancer taking radium-223.  This is the first time a product in the bone category has shown such a survival benefit – neither denosumab or zoledronic acid can claim that distinction.

Unlike the recent regulatory approvals for cabazitaxel (Jevtana) and abiraterone acetate (Zytiga), which focused on the post-docetaxel setting, the ALSYMPCA trial included not only those who had already received cytotoxic therapy, but also pre-docetaxel patients, who were unable to take chemotherapy.

As Dr Parker mentions in the interview that he kindly gave in Stockholm (the first video interview on Biotech Strategy Blog), radium-223, assuming it gains regulatory approval, will provide a new treatment option for the considerable population of men with bone metastases who may be too weak, too old or otherwise unable to take chemotherapy such as docetaxel.

Radium-223 is, therefore, potentially good news for this “neglected” population of prostate cancer patients.

In the video interview, Dr Parker talks about why he believes combining radium-223 with abiraterone acetate (Zytiga) makes sense.

He also talks about some of the challenges that radium-223 still faces, such as how to monitor treatment and work out the optimal dose.  It is hard to believe that Algeta/Bayer would undertake a phase 3 registration study of a novel bone targeted agent without any bone imaging in the protocol!

As Cora Sternberg mentioned in the educational session at EMCC 2011, in advanced prostate cancer, “80% of the disease is in the bone.radium-223 is an exciting radiopharmaceutical that is likely to be “practice changing” once approved.

That’s not to say there are not going to be challenges and issues with its commercialization.  Algeta/Bayer have a lot of work to do now that it is clearly on fast track for FDA approval next year.

Dr Parker also mentions in his interview that radium-223 is a weak alpha emitter and the radiation can be blocked by paper or glass. It therefore requires no special facilities, such as lead lined rooms, for its administration, unlike beta emitters.  The latter have been challenging commercially in the past for this reason.

However, it does require a radiopharmaceutical license, which means that community based oncologists and urologists in the United States will most likely have to refer patients to receive their injection at an approved facility where there is a nuclear medicine/radiology department or equivalent expertise.  In Europe, this is less of an issue given most cancer patients are treated in outpatient clinics associated with hospitals, whereas in the US, the majority of patients are seen in the community setting.

Despite that, it is hard to believe that radium-223 (Alpharadin) will not have a major impact on the advanced prostate cancer market if it can be commercially supplied without difficulty and the details are worked out on how to use it optimally and monitor progress. I am sure we will hear more on these issues at cancer conferences next year.

Looking at the other indications for bone targeted agents such as denosumab and zoledronic acid, radium-223 or a similar radiopharmaceutical could offer potential benefits in other tumor types such as breast cancer, were there are also skeletal related events (SRE’s) associated with treatment.

The video interview I did with Dr Chris Parker is well worth watching, and I am grateful to him for taking the time out of his busy schedule at the recent Cancer Congress in Stockholm. Since this is a first for Biotech Strategy Blog, do let me know if this is something you’d like to see more of moving forwards.

Challenges & opportunities for radium-223 (Alpharadin) in advanced prostate cancer – an interview with Dr Chris Parker 

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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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There is a lot of focus at the annual meeting of the American Urological Association (AUA) here in Washington DC on metastatic castrate resistant Prostate Cancer (mCRPC), and the recently FDA approved adrenal steroid inhibitor, abiraterone acetate (Zytiga®).

Drugs in development that target the androgen receptor, such as MDV3100, are also generating a lot of interest from urologists.

However, Oliver Sartor (Tulane) in the Saturday morning satellite symposia that I attended, focused on emerging therapies in CRPC, beyond the androgen axis. His hypothesis:

“Cancers are devious and some of the mechanisms of AR activation appear to be ligand-independent and resistant to all current androgen-axis targeted therapies.”

What this means is that focusing on adrenal steroid inhibition or blocking the androgen receptor may not be sufficient to prevent disease progression. If we are looking for a Prostate Cancer cure, then will it take multiple drugs, including those that target various stromal sites? That is the intriguing question that Sartor raised.

Indeed, if there is one take home from this meeting, it is that the “desert” of prostate cancer therapies has now blossomed into a multiplicity of potential new therapies and development, which will mean that urologists and oncologists will soon be spoilt for choice as abiraterone and MDV3100 are not the end of the story.

Sartor highlighted some interesting ones on the horizon to watch out for:

Alpharadin: This is a bone targeted therapy that uses radioactive Radium 223 to kill cancer cells. It is being developed by Norwegian company, Algeta in partnership with Bayer Schering Pharma AG. The 900 patient phase III trial completed accrual earlier this year in Jan 2011. Phase II data was published in the Lancet in 2007 by Nilsson et al. Data from alpharadin will be “coming soon” according to Sartor.

XL-184 (cabozantinib): Activated MET is highly expressed in prostate bone metastases. Exelixis XL-184 is a small molecule tyrosine kinase inhibitor that specifically inhibits both MET and VEGFR2.

Data from a phase 2 study of XL-184 in castrate resistance patients was presented last year at the EORTC-AACR-NCI Symposium on Molecular Targets and Cancer Therapeutics in Berlin by David Smith et al (Abstract 406).

Both XL-184 and alpharadin would be potential competitors to Amgen’s denosumab (Xgeva®).

Other new products in development “Beyond the Androgen Axis” that Dr. Sartor mentioned included Prostvac-VF, BPX-101 and ipilimumab. A phase III trial of ipilimumab, both pre- and post- docetaxel is now underway in mCRPC. A phase III trial of Prostvac-VF will start later this year with 1200 patients in a placebo controlled study with minimally symptomatic, castration-resistant metastatic prostate cancer patients.

Over the next few years a lot of data may emerge on exciting new treatment options. Coupled with the basic research that is going on, tremendous progress in the treatment of Prostate Cancer is already taking place.

According to Sartor “multiple drugs will be necessary to cure mCRPC and that is our greatest challenge today.” Major progress is now being made towards this.

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