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PHARMA: Where are the orphan cancer drugs? by The Industry Veteran

Greg Pawelski’s recent posting here about whether cancer care could improve has drawn several responses, many of which I’m trying to redirect back into the comments section.  One, however,  that deserves its own posting is from our old friend The Industry Veteran who wonders whether the current model of big pharma itself can sustain itself in the kind kind of designer-drug world Greg is proposing:

Greg Pawelski makes a good point in his post, specifically, that the economic
model under which Pharma companies develop oncology products may be inimical to
the individualized treatment approaches required for the disease(s).  I suspect
that the figurative lumber rooms of the Big Pharma companies are stacked with
discontinued oncology compounds that proved wonderfully effective and tolerable
for 5%-10% of the target candidates but, sadly, they were terribly toxic or no
better than placebo for the others.  In fact, I know that’s the case.  Not long
ago I completed a study for a client to find why the companies are so reluctant
to out-license these moribund compounds.  The overwhelming answer, the one that
dwarfs all the others, is ego of the fiduciary executives.  The executives feel
they would invite serious job trouble by out-licensing an abandoned compound to
a small startup that proceeds to make it a successful brand.
While
Pawelski deplores the one-size-fits-all requirement, that constitutes the
standard among Big Pharma for launching a product. 

Today the Big Pharmas will
curtail development of a product with projected, peak year, global sales of less
than $850 million.  Anything less will not sustain their high fixed costs or
permit the economies of scale on variable expenses that represents their
comparative advantage.  When BusinessWeek asked Pfizer’s CEO Hank
McKinnell if the era of the blockbuster (and the giant Pharmas created to
support such megaliths) has passed, he replied, “Anybody who says that doesn’t
understand our business.”  A small company, however, can derive a large return
on equity/sales/assets from a product that successfully treats 5%-10% of a
comparatively small, target population.  The CEO of such a company probably
won’t receive $50 million annual compensation the way Mr. McKinnell does, but
its stockholders and a reasonable number of patients can benefit when a Celgene
takes an abandoned and despised compound (thalidomide, developed as a
tranquilizer for pregnant women) and brings it to market as a major therapy for
multiple myeloma.

I suspect this dilemma will resolve itself as the
pharmaceutical industry evolves into what Oracle’s CEO, Larry Ellison, once
called the Hollywood approach to drug development.  I’ve written about this
before and don’t wish to repeat myself, but basically this involves the Big
Pharmas limiting themselves to acting as sources for development funding and
distribution, while independent producers (biotechs? specialty companies?) buy
the properties and develop them.  Movies today can successfully reach smaller,
more segmented audiences than the big Hollywood studios ever could during the
Mickey Rooney, Judy Garland days.  Unfortunately a lot of people will needlessly
die of cancer before Andy Hardy grows up and tells Louis B. Mayer to go screw
himself.  But hey, in a country that twice elects a wannabe redneck as
president, the market is sacrosanct and its pace of Darwinian change is all we
can expect.

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5 replies »

  1. Two years later, Angelo De Palma, PhD, writes in Pharmaceutical Commerce what The Industry Veteran talks about in this posting.
    Personalized medicine represents a radical departure in the pharma business model with technologies for personalizing drug treatments – for identifying responders and individuals likely to experience serious side effects.
    http://www.pharmaceuticalcommerce.com/frontEnd/main.php?idSeccion=560

  2. I don’t think Neal Deoul can say too much about his therapy now. He died in 2003, from a long term illness (probably cancer) I found his obiturary on a web site.

  3. There are at least a half dozen empiric regimens that no honest clinical oncologist would say are not equally likely to work as the others in an average patient. Let us say that we have a test which has been shown to be as accurate in predicting response and survival to chemotherapy as is the case with bacterial culture and sensitivity tests (which everyone uses without controversy). And the test shows that three treatments look poor, one looks fair, and the last two look good. So now the oncologist narrows his choices to the final two and then factors in his or her clinical judgement in making the final choice.
    I think that a savvy cancer patient should ask his oncologist to show the patient the survival curves for a given recommended form of treatment, including the survival of patients treated on phase II and phase I trials which the doctor may recommend. The patient could also ask the laboratory for the survival curves of patients for whom laboratory tests have been ordered. In the absence of survival data directly pertaining to the recommended treatment or test, the patient could then listen to explanations of why such data are not available. And then decide as to the best course of action.
    In the case of ovarian cancer, after 25 years of prospective, randomized clinical trials to identify the best treatments to give to the average patient, there has been absolutely no progress. A meta-analysis of all trials showed that there was no difference. During those 25 years, along came Taxol. Two large clinical trials showed that Taxol/Platinum combinations were better than single platinum regimen. And Taxol became one of the most remunerative cancer drugs of all time. So Taxol/Platinum became “standard” therapy.
    But then two more very large trials were done, showing that there was no advantage to giving Taxol/Platinum over single agent platinum (like Carboplatin). And Taxol/Platinum also wasn’t any better than another non-Taxol combination (not previously tested against Taxol/Platinum). But Taxol/Platinum remained “standard” therapy. Now that Taxol is off patent, some academic oncology groups have (as their major ovarian cancer project) clinical trials to show that Platinum/Taxotere (a drug like Taxol, but on patent) can now be the new “standard” therapy.
    Patients are treated with Taxol/Carboplatin. If Taxol/Carboplatin doesn’t work, they’ll be crossed over to Taxotere, a drug which is mostly (if not completely) cross resistant with Taxol, for which the cancer clinic will collect several thousand dollars from the large pharmaceutical company if and when they are treated with this drug.
    All the while doing this, the American Society of Clinical Oncology is refusing to suggest sponsored clinical trials of “cell death endpoint” chemosensitivity testing, because, lacking something patentable or proprietary, all assay-testing laboratories can offer is free assays and not the millions of dollars that a pharmaceutical company can offer to push its Taxotere trials.