Cougar Biotechnology: Stalking Prostate Cancer

by: Bryan Czyzewski posted on: July 02, 2008 | about stocks: CGRB    

Cougar Biotechnology (CGRB) is a publicly traded company focused on developing novel treatments for cancer. The company is developing CB7630 (Abiraterone Acetate), a small molecule for the treatment of hormone refractory prostate cancer [HRPC], and has completed several clinical trials demonstrating its efficacy. The National Cancer Center reports that there are over 186,000 new cases of prostate cancer a year. Of these, 20 percent will be diagnosed as metastatic and will become hormone refractory.

So let's put this into some tangible numbers. This means that the market for HRPC encompasses 37,200 patients per year. Assuming pricing inline with most cancer biologics, ~$40,000 a year, and using a basic model of risk adjusted net present value we hit $825 million, for a $40 dollar value per share. Not too shabby.

Prostate Cancer?

Let's try to understand prostate cancer and how abiraterone fits into the treatment scheme. Prostate cancer is characterized by malignant cells which are both androgen-dependent and androgen-independent. For those cells that are androgen-dependent, a critical level of androgen is required to activate a sufficient number of androgen receptors (ARs) so that transcription of death-signaling genes is repressed. Ninety percent of androgens are produced by the testes, with 10 percent produced by the adrenal glands or the cancer cells themselves.

Prostate cancer is treated basically in two phases which are based on the stage of prostate cancer: a prehormone therapy phase, followed by a hormone therapy phase. The prehormone therapy treatments include surgical removal of the prostate gland, radiation therapy with or without hormone therapy, and "active surveillance" (also known as watchful waiting). Stage IV is known as advanced metastatic prostate cancer and is treated with primary androgen deprivation therapy, which may include castration, and therapeutic disruption of the normal androgen production regulatory pathways. At this point the cancer cells can become androgen ablation insensitive (also called hormone refractory). There are only three therapeutics approved by the FDA to treat HRPC (docetaxel, mitoxantrone, and estramustine) all of which are chemotherapeutics with debilitating side effects, but show an increase in survival to 20 months vs. 10 months when PSA levels drop 50%.

Other commonly used HRPC therapeutics include steroids such as hydrocortisone, estrogens, and ketoconazole. These treatments achieve similar decreases in PSA levels with concomitant survival benefits, although there are severe liver toxicity issues.

Cue the Entrance of Cougar

Results of a phase II trial started in December 2006 of abiraterone in chemotherapy naiive patients announced in February 2008 detailed a 50 percent drop in PSA in 61 percent of patients. A phase II trial started in December 2006 in patients having failed first-line chemotherapy with docetaxel showed 48 percent of patients having 50 percent decrease in PSA and 53 percent experiencing on-going stable disease. Another phase II trial and a phase I trial, started in July 2007 and June 2006 respectively show similar promise with patients who have failed other treatment regimens including chemotherapy, leutenizing hormone analogs and other hormonal therapies. Cougar is definitely doing there homework.

So What Does Abiraterone Do?

Andorgen-independent cells in prostate cancer are not getting their growth boost from androgens produced in the testes, which at treatment levels drop to nil. Ten percent of the normal levels are produced in the adrenal glands, but theories point to cancer cells producing their own testosterone, thereby fueling their own growth. Abiraterone, like ketoconazole, interferes with the cells machinery for adrenal steroid synthesis, but through two very specific pathways, P450 enzymes 17-alpha hydroxylase and C17,20-lyase. This results in far fewer side effects and also inhibits androgen synthesis with tumor cells.

Financially Cougar is Stable

(See report here.) Their burn rate for last year was a little over $18 million. They predict they will need up to $85 million in capital to make it to FDA approval. They have over $96 million in the bank.

Where is Cougar's Competition?

There are no second-line hormonal treatments approved for hormone refractory prostate cancer. Current presecribed therapeutics are manly composed of steroids and anti-androgens.

AstraZeneca (AZN) - Casodex (Bicalutamide)

Studies with bicalutamide, an antiandrogen, show about a 23% PSA reduction. Side effects are milder with impotence observed only in 5% and hot flashes observed in 51%. Casodex has pretty much replaced other antiandrogens as the drug of choice because of its improved side effect profile and has generated blockbuster revenue for AstraZeneca, surpassing $1.2 billion in sales for 2006. It should be noted that there has been no survival statistics calculated for second-line hormone therapies alone. Bicalutamide goes off patent in October 2008

Sanfois Aventis (SNY) - Nilandron (Nilutamide)

Studies with nilutamide, an antiandrogen, show about 29% of patients reaching >50% PSA reduction. Side effects include nausea (25%), hot flashes (67%), and impotence (52%). Nilutamide went off patent in 2001.
 

Schering-Plough (SGP) - Eulexin (Flutamide)

Another anti-androgen, flutamide has a similar PSA reduction efficacy, but side effects include gynecomastia (42%), impotence (100%) and hepatic dysfunction. Flutamide went off patent in 2001.

What Competitors Are in Development?

The table below outlines certain competitors and their respective phases (click to enlarge):

What Does It All Mean?

Results from their phase III trials will be important to determine whether endpoint efficacy will be significant when compared to placebo. Abbott's (ABT) Xinlay showed great PSA responses during their trials but showed no significance with tumor radiological responses (shrinkage, decrease in number or events) and showed significant cardiovascular side effects. This lead to a non approval from the FDA. Sartraplatin has been having some trouble as well. Spectrum Pharmaceticals (SPPI) platinum based chemotherapy showed no significant survival benefits in clinical trials.

Cougar is well placed to take a large share of the premium priced market for prostate therapies if its phase III enpoints are met satisfactorily. There is a huge unmet need for an efficacious therapy with minimal side effects that has significant survival benefits. With the dismal performance of Abbott's Xinlay and Spectrum Pharmaceuticals' Sartraplatin, Cougar Biotechnology may take the lion's share.

Disclosure: none

This article has 10 comments! Add yours below...

Bryan Czyzewski

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This article has 10 comments:

  •  
    Seeks The
    Truth
    Jul 02 01:09 PM
    Cougar has a dirty little secret that taints their "good news."
    It's unfortunate that you aren't aware of the issue or were aware and failed to comment.

    Dr. Howard Scher is listed as being involved with the company as an advisor and I suspect that he is also a stockholder. The same Dr. Scher, knowing that Cougar has been working on a chemo-therapeutic agent to fight Prostate Ca, helped wage a successful war to prevent Dendreon's Provenge, a new and revolutionary immunologic vaccine for the same late stage Prostate Ca from being approved by the FDA in May of 2007.

    Dr. Scher also failed to list his relationship with Cougar on the COI forms required by the FDA before he sat on an advisory committee that reviewed Provenge. Why??
    Interestingly enough, the same Dr. Scher was deeply involved with another company called Novacea that was developing a product that would be a competitior to Dendrion's product.
    Another "coincidence?&quo...

    The PV advisory committee ultimately voted 17-0 <!!> that Provenge was SAFE and 13-4 <!!> that Provenge was SUBSTANTIALLY effective, the FDA's own measure of success. This should have maent an easy approval for the immunotherapy.
    Not so. Scher and Maha Hussain M.D., another chemotherapy advocate, wrote letters to the FDA opposing Provenge approval that were conveniently leaked to the press .
    Perhaps not so shockingly, the FDA, in a near unprecedented move, declined to approve Provenge...asking for "more data."

    Oh, did I forget to mention that Dr. Eric J. Small, another Urologist heavily involved in PCa research, was involved with Cougar??
    He was supposed to be on the panel reviewing Provenge too, but never showed up for the meeting, citing travel problems.
    Or maybe his conscience held sway when he considered his own conflict of interest.
    Would you be surprised to know that not a peep has been heard from Dr. Small about the Provenge debacle since early last year??
    Not me!!

    So, Drs. Small and Scher are BOTH listed as being on the Cougar Scientific Advisory Board. Both have vested interests in promoting chemotherapy for late stage prostate cancer and Scher at least, made an all out effort to throttle a new, exciting and revolutionary product that was SUBSTANTIALLY effective in prolonging survival in an otherwise fatal diagnosis for TENS of THOUSANDS of American men who die every year from this deadly cancer.

    Shame on Scher for not revealing his many conflicts of interests before sitting on a panel that was judging a competitive product.

    Shame on Small for not showing up to defend Provenge and then not speaking out against his colleague's actions.

    Shame on the FDA for rejecting a fantastic new product that would prolong survival in men with the death sentence of advanced prostate cancer.

    And shame on EVERYONE who has looked the other way while this travesty against American men continues to play on.

    What the hell is happening to our country???

  •  
    kyoto27
    Jul 02 01:17 PM
    You say:

    "There is a huge unmet need for an efficacious therapy with minimal side effects that has significant survival benefits. With the dismal performance of Abbott's Xinlay and Spectrum Pharmaceuticals' Sartraplatin, Cougar Biotechnology may take the lion's share."

    With all due respect, the odds right now look appear to tilt more in favor of Dendreon's Provenge taking the 'lion's share' following Provenge's IMPACT trial interim results (this year) or final 2H09. With virtually no side effects, and very significant survival benefits --not to mention a positive FDA AC panel recommendation already in it's pocket, there is very little not to like about Provenge's odds to run the table. And remember, Provenge approval also validates Dendreon's 'platform technology' which opens the door to a paradigm shift in how cancer will be treated in the 21st century.

    We live in exciting times....




    Disclosure: none
  •  
    Bryan
    Jul 02 04:09 PM
    Provenge looks great but has some drawbacks too, as does GVAX. Both require infusions with GM-CSF, an immune stimulator. Many results with immune modulation therapies can be actually attributed to the immune boost seen with adjuvant. Provenge and GVAX also seems to work well only in a subset of the HRPC patients.
  •  
    Tony F
    Jul 02 04:38 PM
    Bryan, nice write up on Cougar Bio and their HRPC product.

    I have to side with the 2 above comments in that Dendreon's Provenge--in its definitive 3rd Phase III trail--is years ahead of ALL others competing in this field.

    Additionally, Provenge had an outstandingly positive AC panel recommendation of approval and the FDA has given it an "Approvable" status already.

    Dendreon states that the Interim look on this latest clinical trail will come in 2H08 which started yesterday and extends thru Dec 31st--THIS YEAR!

    If the Interim Look falls short, the Final Look is slated for 2H09... within more 364 days....

    You mentioned how great Courgar's product is in reducing PSA readings, but I didn't see a single word about "Survival"..... which is now the "Gold Standard" in rating cancer therapies...

    Provenge has shown in its past 2 clinical trails to extend "Survival" in 33% of treated patients vs 11% in the control arm... and outstanding increase in survival with a corresponding significantly higher "Quality of Life" for treated patients when compared to chemotherapy.

    Don't take my word for the above... check it out yourself and see how Provenge is going to be the new "standard of care" in HRPC patients and the Dendreon cassette technology will be extended to cancers such as ovarian, breast, liver, lung, etc.... and it's going to doing so much sooner than Cougar and all the others.
  •  
    Bryan
    Jul 02 06:07 PM
    I hope Dendreon's Provenge can deliver on its promises. THe 34% increase in survival rate is very promising. My one qualm is that placebo in their phase III trials were not done with their immune adjuvant, therefore the response rate you see may not be due to the treatment process that isolated APC's receive but to the stimulatory effects of the GM-CSF. If this is the case, then the treatment could potentially be even more promising. Anything that improves time to progression and survival is a welcome treatment in HRPC. Both treatments Dendreon's and Cougar's fall short, time to progression for Provenge and no survival statistics for abiraterone.
  •  
    kyoto27
    Jul 03 01:14 AM
    Bryan, you say:

    “Both treatments Dendreon's and Cougar's fall short, time to progression for Provenge and no survival statistics for abiraterone.”

    Did Provenge really miss ‘time to progression?’

    The p value for the primary endpoint of cancer progression was p=0.052, barely missing the p=0.050 threshold. For Howard Scher and Maha Hussain, this narrow miss was blown up to be an utter failure. They said that because the p value did not reach 0.050, then all additional data (including survival) should be discarded. Basically, their position was that because the odds of being successful in progression were only 94.8% and not 95.0%, there was no correlation between the two metrics and the 99.0% survival odds should be thrown in the trash.

    And remember, the overall survival p value in 9901 was 0.01, easily beating the p=0.05 threshold. This goes to the crux of the anger of the Provenge advocates. Statistical significance on survival is the "gold standard" by which the FDA judges all oncology treatments, and Provenge met it with flying colors in the 9901 trial.



  •  
    Jose
    Mcintryre
    Jul 03 09:28 AM
    Bryan, write about prostate cancer and you're bound to pull in DNDN shareholders that are too dense to figure out that its not an either or, all or nothing market.

    One competitor you are missing though is Medivation-MDVN. Since they don't need to be administered with prednisone it may have more of an opportunity to move to front line than Cougar. But that said, its not all or nothing, they both can co-exist, everyone will fail on prostate ca eventually. The whole goal as I see it is to delay moving to chemo as long as possible. Cougar has about a 1.5 year head start on MDVN.

    Disclosure: long cgrb and mdvn
  •  
    Dad has 38
    PSA
    Jul 04 11:23 AM
    Are there any clinical trials going on that I could have father on?

    He has a PSA of 38 right now and we are contemplating his options.

    Please answer here as I don't want my email spammed by bots. I will bookmark the site and check in. We are in California.

    July-4th, 2008
  •  
    Jose
    Mcintryre
    Jul 06 10:05 PM
    Sorry about your father. A psa of 38 is actually very low. Maybe you have the number wrong.

    I would suggest contacting UCLA medical or perhaps there's other major cancer centers in Cali. Cougar's abiraterone is the hottest drug in prostate cancer right now, so that's one to look into if he qualifies for treatment. Good luck.
  •  
    PeakOiler
    Jul 22 10:15 AM
    There's a very positive article on Abiraterone in the Guardian today (July 22, 2008).

    news.bbc.co.uk/2/hi/he...
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