“Competitive analysis” in the development of drugs for advanced prostate cancer


So the other morning your sitemaster learned that a relatively new FirstWord Therapy Report had come out that dealt with future use of biopharmaceuticals in the treatment of progressive and advanced prostate cancer. These types of report are detailed and comprehensive and valuable to (a) companies that work in the biopharmaceutical industry and (b) companies (and affluent individuals) that specialize in investing in the biopharmaceutical space. Anyway, your sitemaster thought it would be interesting to see what was covered in this report, so here’s a quick summary.

The new report (Prostate Cancer: KOL Insight 2016) looks at four key questions:

  • How are newer types of established therapy being sequenced in treatment of prostate cancer and how might that change in the near future based on evolving information about these products and their features and benefits? This question is particularly important for the use of drugs like
  • How might new data from large Phase III and Phase IV clinical trials impact the use of these and other drugs? This question is probably most relevant to the future use of drugs like abiraterone acetate, enzalutamide, and radium-223, for which several large trials are ongoing (using the drugs both alone and in combination with each other)
  • How might completely new drugs impact the marketplace in the near future? This is a question that is most likely to be impacted by the results of the ongoing Phase III trial of Prostvac (rilimogene galvacirepvec/rilimogene glafolivec) — and those results are currently expected later this year
  • Finally, what other drugs currently in clinical trials could be expected to have significant potential on the treatment of progressive and advanced forms of prostate cancer?

In trying to address these questions, FirstWord employees and their partners did two different things:

  • FirstWord’s biopharmaceutical market analysts carried out a detailed review of the available data.
  • FirstWord also conducted a series of hour-long interviews with a dozen well-known American and European “key opinion-leaders” (KOLs) in the treatment of progressive and advanced forms of prostate cancer to get their opinions on how they expect treatment patterns to change over the next 3 to 5 years based on the products in the pipeline and how they think results from new and ongoing trials are likely to pan out.

Now your sitemaster should be clear that he has not seen the full report (and he doesn’t have enough money to pay for one either!). However, he has seen reports like this in the past, and so he can make some reasonably intelligent guesses. Here’s what he suspects are some of the most important things that the new report has made some pretty clear predictions about:

  • Will uptake and use of enzalutamide, abiraterone acetate, and radium-223 grow significantly over the next 5 years, and will trial data be able to justify greater use of these products earlier in the disease stage?
    For this to happen, your sitemaster suspects that earlier use of the products will have to come with enhanced benefits in terms of time to disease progression and long-term survival, but without any major increase in the risk for complications and side effects of treatment.
  • Which major trials will be important in supporting expanded used of these widely approved agents?
    The range of such trials is considerable, and we don’t intent to get into all of that here, but they includes uses of the various products alone in some subsets of patients or in combination together in other subsets.
  • Which new products are getting relatively close to approvability (if we assume that the results of major Phase III trials are positive)?
    The obvious ones are Prostvac, apalutamide (ARN-509), and perhaps some rather more “under the radar” investigational agents like DCVAC/PCa (an immunotherapy), ProstAtak (another immunotherapy), and masitinib (a tyrosine kinase inhibitor). All these products are currently in large, randomized, Phase III trials that could lead to product approvals for the treatment of advanced forms of prostate cancer.

Now there are other areas that the report has certainly touched on that are also highly relevant, such as these:

  • What is the clinical and business potential of drugs known as PD-1 inhibitors (like pembrolizumab/Keytruda and nivolumab/Opdivo) in the treatment of advanced prostate cancer?
  • Similarly, what is the potential of drugs known as PARP inhibitors (like olaparib/Lynparza) in the treatment of advanced prostate cancer?
  • Will CAR-T-type treatment (from companies like Juno Therapeutics and Kite Pharma) be an option for the treatment of advanced forms of prostate cancer (and will the benefits outweigh the risks of using these forms of treatment)?
  • Is there anything really interesting on the horizon that people like your sitemaster haven’t been able to spot yet?

One thing that your sitemaster did become aware of recently as a result of a random Google search is that a company known as Churchill Pharmaceuticals is developing a new formulation of “submicron” abiraterone acetate. He assumes that such a formulation may allow for delivery of similar effectiveness of the abiraterone at a lower dose of the drug than is currently used in Zytiga. When it might be possible to see such a product on the market may depend as much on legal issues of patentability as on the clinical effectiveness and safety of the agent. He would expect the FirstWord Report to be able to offer greater insight into issues like this.

What is important for the patient community is simply the awareness that this type of “competitive information” analysis is going on constantly in the background. And wise developers of on-market and development-stage drugs (and their investors) keep an eye on reports like this with considerable attention to the details. Of course if you have a spare $8,000 or so, you should feel free to buy a copy for yourself! Your sitemaster can’t help you with that one!

4 Responses

  1. Is there a summary somewhere of the increased life expectancy and side effects/QOL impacts from use of each of the new drugs or combinations thereof or is it so variable from man to man that use of “median” additional survival is meaningless?

  2. Bob:

    I am not aware of a really good and clear summary of these issues for all of these different drugs.

    The basic problem is that individual patients can have highly variable responses to all of these types of drugs (in terms of both their effectiveness and their side effects). If you look at the full prescribing information for each drug, you will be able to see what I mean, but to pick just one example …

    Provenge offers a median survival benefit of just over 4.0 months compared to a placebo in men with early mCRPC based on data from the original clinical trials, but the range of that benefit was from 0 months to about 60+ months. But the number of men getting those very high levels of benefit was small.

    Similarly > 95% of men in the trial who got Provenge had at least one side effect that seems to be associated with treatment, but so did > 90% of the men who got the placebo treatment! So we really can only make judgements about the side effects that were clearly much more common in the Provenge arms of the trials (e.g., > 50% of patients treated with Provenge had chills associated with their treatment as compared to ~ 11% of the men treated with the placebo), but that also means that > 40 percent of the men treated with Provenge got no chills at all (and there are some data to suggest that it was the patients who got chills and fever when treated with Provenge who were among the ones who were most likely to be the ones having the most robust response to treatment).

    Thus, as you can see, developing the sort of summary chart you are talking about would be extremely complex but it really wouldn’t be very informative in helping to tell an individual patient what he might actually experience as an individual.

  3. Unfortunately we have only a few studies reporting sequences of first-, second-, and third-line treatments of advanced prostate cancer, so there are limited empiric data supporting any thoughts of the best sequence of the life-prolonging drugs.

    I am puzzled. St. Gallen with Gillessen is working on an update of outcomes of testicular germ cell tumors and collect a database of > 10,000 patients to design a prognostic model on which to base advice about treatment. Meanwhile, the St. Gallen recommendation for treatment of advanced prostate cancer (much more frequent) is based largely on the opinions of the experts. It is not based on a database of recently treated patients. So it seems like testicular germ cell cancer is a “darling” cancer.

    How come there is such a great divergence between the need for research and the research done?

  4. Dear Finn:

    I haven’t researched this carefully but I suspect that the situation is a function of the fact that we know how to actually cure many, many cases of advanced testicular cancer, and so what is going on with the St. Gallen initiative in that case is probably a very careful analysis of data from 10,000+ patients who are all being treated in what is basically a very similar set of ways, with small variations to try to improve on the basic treatment paradigm.

    By contrast, we are able to cure very, very few cases of advanced prostate cancer and we are still evolving the base pathway (through studies like the STAMPEDE trial and many others). There are now numerous trials ongoing to investigate whether there is a “best” order in which to deliver care using the available therapies for advanced prostate cancer, but just as our treatment paradigm has recently been changed radically by the data from the CHAARTED and the STAMPEDE trials, it could be thrown for a loop yet again by data from the ongoing trials of drugs like Prostvac and ARN 509 and others.

    I would submit to you that there is actually an enormous amount of ongoing research into the ability to appreciate what “the best” form of treatment for prostate cancer might be. However, unlike the situation with testicular cancers, since we haven’t got to a point at which we have any type of really well-defined pathway that can come close to finding a way to “cure” most men with advanced prostate cancer, most of that money is going into seeking major improvements through the use of completely new drugs and combinations of those drugs with each other as opposed to seeking to establish improvements in a well-defined pathway.

    If you look at this article that summarizes the findings of the first St. Gallen conference on advanced prostate cancer, you will note that it lists out a “top ten” list of key, controversial issues affecting the treatment of advanced prostate cancer. Without resolution of several of these issues, it is near to impossible to establish a set of “best practices” in the treatment of micrometastatic and metastatic prostate cancer. However, having said that, we have already come a very long way from where we were 20+ years ago when I developed the first iteration of The Prostate Cancer InfoLink. At that time the only forms of treatment for men who progressed to hormone-refractory prostate cancer were high-dose ketoconazle (highly toxic and with no survival benefit), mitoxantrone (which was entirely palliative and simply suppressed pain symptoms for a relatively short period of time), and corticosteroids such as prednisone and dexamethasone.

    By the end of this year, I am optimistic that we may have two more drugs that will have been shown to have life-extending impact in the treatment of men with metastatic prostate cancer, taking us to a total of seven such agents since docetaxel (Taxotere) was first approved for the treatment of hormone-refractory prostate cancer in 2003, followed in succession by sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide, and (I hope) Prostvac and perhaps one more.

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