How to get really bad investment advice


As we get closer to the annual meeting of the American Society of Clinical Oncology (ASCO) — to be held at the beginning of June — the investor community is beginning its annual frenzy of speculation about exactly what new information will be presented at the meeting about development stage and marketed drugs.

We suspect that the average patient may not be fully aware of the rampant hysteria that can overtake some members of the investment community at this time of year, so (for your entertainment) here is a link to a sample piece of hype that we came across this morning — filled with inaccuracies and over-promises.

For starters, in the world of prostate cancer, we don’t expect either Medivation (MDV3100) or Johnson & Johnson (abiraterone acetate) to be presenting major new data at the ASCO annual meeting this year.

The first of the two Phase III clinical trials of MDV3100 (the AFFIRM trial) is fully enrolled, but we aren’t expecting this trial to be completed until late in 2011 at the very earliest. The second of the two Phase III trials of MDV3100 (the PREVAIL study) is still enrolling patients. There is no way that Medivation will have data from either of these two trials to present.

With regard to abiraterone, we already know the result of the trial in men who have progressed after docetaxel-based chemotherapy. It showed a median 4-month survival benefit for the men treated with abiraterone, and the outstanding question is not what new data will be presented at ASCO but whether the U.S. Food & Drug Administration will actually approve this drug in time for Johnson & Johnson to be able to promote its approval to the attendees at the ASCO meeting in the exhibit hall. Again, we don’t expect data from the clinical trial of abiraterone in chemotherapy-naïve patients until very late in 2011 or (more likely) some time in 2012, although this trial (unlike the PREVAIL trial) is fully enrolled.

We would warn patients not to start making treatment decisions on the basis of most of the hyperbole that they may see in the financial media. There are good and reliable sources of information about the actual clinical status of the majority of prostate cancer drugs in development, and if you are in doubt, you can always talk to your doctor. Until a company can complete the necessary Phase III clinical trials and submit information to the relevant regulatory authorities such as the FDA and be given regulatory approval to market the product, the only access to investigational drugs like MDV3100 and abiraterone is through clinical trials.

And for any in the investor community who happen to be reading this article, beware of the type of guidance appearing in the link above. It was written by someone who clearly knows little to nothing about the prostate cancer marketplace.

Now we do expect to see interesting information presented at ASCO this year. There may even be some surprises in the prostate cancer space. We do also expect to see abiraterone get approved for the treatment of men with progressive prostate cancer following treatment with at least one or perhaps two types of chemotherapy. Furthermore, we are optimistic that this approval will come before June 1, 2011. However, we are not expecting data from any other large Phase III clinical trials of development stage drugs for prostate cancer at the this ASCO meeting. On the other hand, between late 2011 and the end of 2013 we are expecting an absolute flood!

One Response

  1. Thanks for your insights into the timelines for trial results and approvals.

    This past April I participated in the annual meeting of the American Association for Cancer Research as a three-time veteran of the AACR’s Scientist↔Survivor Program. Dr. Sawyer, the lead investigator for MDV3100, gave an enthusiastically received presentation about the drug and the trials.

    I am looking forward to encouraging results and ultimate availability of this drug.

    I do have one substantial issue with the approach taken: the definition of “castrate resistant” as “medical or surgical castration with testosterone less than 50 ng/dl”. As a veteran of intermittent triple androgen deprivation therapy for over 11 years now for a challenging case as my sole therapy, I’ve become familiar with how doctors I consider experts handle this therapy. They are all convinced that using a “testosterone less than 50″ as the indicator of castrate resistance (with a rising PSA or other clinical indications of progression of course) is inadequate: the standard needs to be a testosterone less than 20 as one key indicator that blockade is not working.

    In essence, many men with rising PSAs and testosterone levels between 20 and 49.9 may well still be able to benefit from effectively administered and managed hormonal therapy. Several expert clinicians have reported seeing about 10% of men whose blockade is inadequate due to delivery issues or extra rapid clearance of the drugs due to their personal biologies, both of which can be corrected fairly easily.

    Some men on single drug (LHRH agonist) hormonal blockade experience a ramping up of testosterone — far below the normal level but still significant — due to above average indirect production of testosterone via the adrenal glands, after the body’s endocrine system has signaled the glands that the testosterone level is below normal. That can be addressed with an antiandrogen, with generically available bicalutamide being the drug of choice for first line therapy. If and when the first-line antiandrogens fail, ketoconazole (with hydrocortisone) has a good track record for restoration of success. However, the MDV3100 protocol does not require men to have tried an antiandrogen as part of their approach, so again we don’t have assurance that hormonal blockade had truly failed in the trial participants.

    Moreover, a substantial proportion of other men do not have a sharp drop in DHT even though their testosterone may have plunged. Furthermore, even when men have shut down testicular testosterone production and are taking an antiandrogen to block the androgen receptors (AR), DHT has substantially greater affinity for AR and can muscle out the antiandrogen at the AR site, enabling it to continue fueling the cancer. That too can wreck a hormonal blockade program, but the problem is also easily solved with a 5-alpha-reductase inhibitor drug (finasteride or Avodart). However, the MDV3100 protocol does not address DHT level as a criterion.

    These are the key points I see that lead to the conclusion that the men in the MDV3100 studies may not be truly castration resistant, that hormonal therapy has truly run its best course for them and is no longer adequate. These problems, however, seem to me to be unfortunate for the patients, but not key to the trial results. Randomization and double-blinding should give good assurance that we will see valid results from the MDV3100 trials.

    From a patient standpoint, it’s good to look forward to the approval of MDV3100, but it’s very good to know we now have triple blockade therapy plus bisphosphonate support, and that the cost has plunged as the main elements go generic (bicalutamide, finasteride, and alendronate already generic). The one element that is not generic yet is the LHRH agonist component, but patents for Lupron are set to expire in 2013. Is it wrong to think it will go generic about that time?

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