Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Recently, ASCO held its annual symposium on GI cancers, which covers a variety of tumour types including pancreatic, colorectal, gastrointestinal, renal and prostate cancers. In this blog review, we will concentrate on an update on prostate cancer.

There is a clear unmet need in hormone-resistant prostate cancer (HRPC) because conventional anti-androgen therapy can stop working after a few years of treatment, leaving a population of men whose cancer no longer responds to treatment and who have a limited life expectancy. Taxotere, a chemotherapeutic agent, is the only FDA-approved drug to treat HRPC and was approved in 1996 on the basis of a 2.5 month survival advantage.  The therapy also has significant adverse events associated with it, including myelosuppression and risk of febrile neutropenia. 

Much of the noise surrounding new treatments for HRPC have centred around Cougar Biotech's abiraterone and Dendreon's Provenge.  

The former announced an update in chemo-naive HRPC. Data on the 31 evaluable patients treated in the trial were reported in a poster by Ryan et al.  77% patients experienced a decline in prostate specific antigen (PSA) levels of greater than 30%, 71% experienced a PSA decline of greater than 50% and 26% experienced PSA declines of greater than 90%.  Median time to PSA progression had not yet been reached, with patients continuing to be treated for 10+ months.  Of the 33 evaluable patients with tumour lesions that were measurable by the RECIST criteria, treatment with abiraterone resulted in partial radiological responses in 24% patients, stable disease in 39% patients and progressive disease in 12% patients; 24% patients were still awaiting radiographic disease assessment.

Cougar has a special protocol assessment for two planned registrational trials of abiraterone – one in a post-chemotherapy population and the other in the pre-chemo/post-androgen deprivation therapy population.   Data from the smaller trial, in the post-chemo population, could be available late this year or early in 2010.  The primary endpoint is overall survival.  

The main reason for all the excitement, I suspect, is because the therapy is a pill and early results from previous announcements suggest that it may be much better tolerated than Taxotere, which will be much better for the elderly population for whom it will be targeted towards.

One therapeutic mentioned at the meeting that I found interesting and novel was Mediavation's MDV3100, an androgen receptor antagonist.  Researchers at Memorial Sloan Kettering in New York presented the initial phase I/II data on PK and anti-tumour activity.  They concluded that MDV3100 was: 

"Generally tolerated with encouraging anti-tumor activity as assessed by PSA declines, CTC changes, imaging findings, and time on treatment. The data suggest a dose-response trend with consistency across endpoints." 

As a result of this trial, a phase III protocol has been approved in HRPC.  Clearly a compound to watch over the next couple of years, although it is too early to say how it may pan out.

Gene therapy is another technology that has seen more misses than hits.  The National Foundation for Cancer Research hopes to change that with an interesting approach being tested by Dr Paul Fisher that is basically:

"A genetically reprogrammed virus, called “Cancer Terminator Virus”
(CTV). CTV is designed to specifically infect tumor cells and destroy
them by replicating itself within the cells. The secret of restricted
tumor targeting lies in a special control system employed in CTV. Dr.
Fisher’s therapeutic virus employs a special gene element he discovered
earlier which can only turn on virus replication in tumor cells, but
not in normal cells. Once turned on, the virus copies itself inside a
tumor cell and eventually causes cell death. On the other hand, the
normal cells are prevented from being harmed because CTV can not
replicate in them. This smart control system ensures that this small
biological killing machine only fires on tumor cells."

You can read more about the concept here.

In 3 hours time, Dendreon are hosting an update on the phase III data for their cancer vaccine in prostate cancer, Provenge (sipulucel-T), the results of which are eagerly awaited by many health care physicians and patients alike.  D9902B, also known as IMPACT (Immunotherapy for Prostate Treatment), is an on-going Phase 3 trial and will effectively seal the fate of the drug with the FDA and ODAC. To say the the vaccine has had a chequered history is an understatement.  The previous trials, D9901 and D9902A were not sufficient to gain approval on their own and arguments for and against the drug have raged for a few years now.  The D9901 trial showed a significant increase in survival of 4.5 months over placebo with a hazard ratio of 1.7.   

On March 29, 2007 it was agreed with the FDA that a positive survival result from the IMPACT trial would allow Dendreon to seek approval.  The target indication was for treatment of men with metastatic androgen independent prostatic adenocarcinomas.  Once the webcast has broadcast today, I will update this post for the new trial data.


The IMPACT data turned out to be more interesting than many expected.  Dendreon announced this morning on the analyst call that:

"The pivotal Phase 3 IMPACT study of PROVENGE® (sipuleucel-T) in men with advanced prostate cancer met its primary endpoint of improving overall survival compared to a placebo control. The magnitude of the survival difference observed in the intent to treat population resulted in the study successfully achieving the pre-specified level of statistical significance defined by the study's design. The safety profile of PROVENGE appeared to be consistent with prior trials."

The company described the optimal patient for the vaccine as having metastatic, 'androgen-independent' prostate cancer for which Provenge will be a front-line treatment option, putting it head to head with standard chemotherapy treatment, Taxotere (docetaxel). No comparative data between the two treatment options is, however, available at this time so if the FDA approves the product, patients will have a choice of first-line therapies.

No further substantial clinical details were announced other than the trial data wiil not be released until American Urological Association Meeting in Chicago at the end of this month in order to maintain the embargo. Pricing, if the vaccine is approved, was vague. The per-patient price has not been set, but it is expected to be in similar range to other oncology biotech products (I read that as meaning expensive).

Dendreon's BLA submission will be a "type 2", which gives FDA 6 months to respond.  If approved, the drug could be on the market by end of 2009/beginning of 2010.  The company has estimated that 100 sales reps will likely be sufficient to address the North American market, including both oncologists and urologists.

Watch this space on April 28th when the full data will be presented at the AUA meeting.  In the meantime, the stock price surged from $7 to $24 before settling back at $17 today on the back of the positive survival data.
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3 Responses to “Dendreon's Provenge and other hot drugs in Prostate Cancer”

  1. Lee Buckler

    Great post as usual Sally.
    Re: the BLA timing for Dendreon, CEO Mitch Gold was pretty clear on the call today and it also states in today’s press release that they intend “to file an amendment to its existing Biologic License Application (BLA) in the fourth quarter of this year”. (I think there were from lessons learned in the first go-around and they want to make sure this submission is all but perfect.)
    Seems to me that will almost certainly put an FDA decision into 2010 (maybe Q1 but more likely Q2) unless they were to file in October and the FDA decided within a few weeks rather than taking 3-6 months.

  2. Sally Church

    Hi Lee, yeah I heard Gold say that too, but really, if they have the data plus the survival results of the previous 2 trials it is hard to see how it could take so long to put the filing together.
    Either they have the data or they don’t. It will be interesting to see what ODAC make of it, though.
    Mind you, it may not be a dead cert if this article in the FT is anything to go by:,dwp_uuid=e8477cc4-c820-11db-b0dc-000b5df10621.html

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