by Daniel R. Hoffman, Ph.D.
Last week Pfizer and Johnson & Johnson halted development of their late-stage drug for Alzheimer's, bapineuzumab, because it could not stop progression of the disease. Few people in pharma or the investment community were surprised at bapineuzumab's failure, as most odds makers put its chances for success at approximately 25 percent.
Four years ago, mid-stage trials of the drug showed similar results as well as a potentially dangerous incidence of brain swelling. Those findings, in fact, led many scientists to deride the entire "hypothesis" by which bapineuzumab's proponents justified its use as an Alzheimer's treatment.
In the days following bapineuzumab's failure, some commenters even wondered why Pfizer and J&J decided to risk almost half a billion dollars by advancing such an inauspicious compound to Phase 3 trials. Typically 75 percent of all costs for developing a new drug occur in Phase 3, so one might think pharmas would advance only their most promising compounds to this level.
Twenty-five years ago, that was more or less the case. Industry lore at the time held that when a Merck or a Squibb put a drug into Phase 3 testing, someone could bank on the fact that it would receive regulatory approval.
The fact that pharmas currently will risk big money on developing long shot compounds immediately reveals a couple of indisputable facts. First of all, the science just isn't there for developing drugs that substantially advance the standards of therapy beyond what's already available. The eventual payoffs and the resources going into curative therapies mean the breakthroughs will eventually come, but that day is not yet here.
Secondly, auspicious candidates for development aren't just rolling down the pipeline, so it's not as if pharma researchers can pass on the dim prospects with the knowledge that better ones will soon arrive to replace them.
But why do pharmas advance poor prospects to expensive, Phase 3 testing and throw half a billion dollars of shareholder money out the window in the process?
The former head of Pfizer's R&D, John LaMattina, believes he has an answer. He recently published an article in Forbes where he attempted to justify the decision Pfizer/J&J made to put bapineuzumab into Phase 3.
LaMattina described the frequently acrimonious discussions that take place inside pharmas over making go/no-go decisions after iffy Phase 2 results. His article, however, didn't place even a smidgeon of responsibility at the feet of fiduciary officers and senior R&D people who receive bonuses based upon the number of compounds they advance to Phase 3. Nor did he state that C-suite people uniformly believe they look better to shareholders by throwing a Hail Mary pass against a stacked secondary, rather than limiting their losses by punting the ball.
Also absent were any references by LaMattina to the internal pressure from hundreds of clinical and commercial people at pharmas who would prefer burning shareholder money rather than putting their usefulness in question when the company discontinues work on their drug.
While LaMattina mentioned that high-powered, independent researchers from outside the company typically participate in these go/no-go discussions, he neglected to state that they have a vested interest in the outcome because continuing the clinical testing will bring them opportunities for lucrative research contracts.
So where does LaMattina lay responsibility for this sort of corporate boondoggle? In effect, he writes that patient advocacy groups made the companies do it. Those unrealistic, bleeding-heart, shrieking hysterics threatened to make the two pharmas look bad if they didn't go ahead. The patient groups enlisted support from some of those independent researchers who would otherwise be disgruntled if the companies halted the work, and together, they forced the two multibillion dollar corporations to wade deeper in the big muddy.
Well patient advocacy groups can exert some effect, but basically they stand several rungs down the influence ladder from the greed, ego and similar motives of senior executives. The area where patient advocacy groups scream the loudest concerns the exorbitant pricing of drugs for their respective therapeutic areas. Yet pharmas seldom let these plaintive cries influence their inexorable price increases. Certainly the patient groups didn't deter pharma's industry-wide strategy of pricing as many new products as possible at the vastly higher level of biologicals and, for some, even into the orphan drug stratosphere.
So as the presidential election now moves into high gear, the public receives daily blasts of deception from the campaigns. Is that appreciably worse than half-truths and misdirecting statements that pharma's cheerleaders now communicate regularly?
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