After being buggery-augered with no lube by the New England Journal of Medicine’s finest, it’s refreshing for us minions of Big Bad Pharma and our small company lampreys to read an article in that august journal which moves beyond Angellic knee jerk histrionics.
Alastair J.J. Wood, M.D. offers a proposal for radical changes in the drug-approval process. As Joseph j7uy5, proprietor of Corpus Callosum notes, this is a free access article and a worthwhile read.
Wood’s proposals include severe kicking of the tires for me-too drugs, follow-up on safety after a drug’s launch, demonstration of a real clinical benefit, and encouraging discovery and development of first-in-class drugs. The prospect of extended exclusivity past a drug’s patent lifetime would in theory give the pharma companies incentive to engage in these activities. This might cause some bristling among consumer activists (check out the link below to Boldrin and Levine’s treatise on the evils of intellectual property) since branded drugs are more costly than generics, and exclusivity keeps the higher preiced med out there that much longer. Keep in mind that although generics are cheaper, they do not encourage nor pay for innovation, and honestly, that’s what pharma really needs to focus on now: innovative drugs which will be a genuine benefit for unmet medical needs.
Speaking from the discovery bench monkey’s perspective, there are some notions in Wood’s article which are pant-hootworthy. I particularly like Wood’s incentives for discovery of first-in-class drugs.
I was fortunate to be part of a discovery team (medicinal & early process chemists, biochemists, biologists, pharmacologists) who brought such a first in class compound into the clinic. It’s in Phase II now, and is yielding impressive results against a disease which fits solidly into a major “unmet medical needs” category. The compound is on the FDA fast track. Keeping the safe harbor in sight, at Phase II, there’s still a long way to go and anything could happen, but I can tell you that it is a rush to think this compound could actually make it. If my horse in the race crosses the finish line, it’ll help a lot of patients. The discovery team’s names will not be emblazoned in bold Arial font on the capsule, but it’s pretty much like being authors on a pivotal publication in a well regarded journal. Booyah! So, yes, please give our upper management bosses a carrot to let us bench monkeys do even more new cool stuff in the lab.
Wood comments on the basic science underlying drug discovery and that this largely emanates from the public funded sector. His calm assessment contrasts beautifully with Angell’s near junk-science analysis. We drug discovery scientists love basic research, and when I attend bio-organic chem type conferences, I often sigh and think it must be nice to worry about where the electron is. But financially, it doesn’t make a lot of sense for us to start from scratch. In drug discovery, we’re ready to pounce and apply our expertise to a nifty target which someone has discovered (and reported in a peer reveiwed publication) or which a genomics collaborator has identified. As Wood correctly observes, the academic arena simply does not have the resources to bring a drug to the market. If one believes that drug discovery should also perform the basic science to have legitimate claim to a target and drugs resulting from it, well, then be prepared for extraordinarily expensive drugs and a much longer time to market.
With regard to genomics, Wood notes:
…the number of new drug applications submitted to the FDA has decreased during the past 10 years even though the genomic revolution should have led to an explosion in this number.
In fact, a large number of targets have been identified via genomics but they are anything but readily tractable. The low hanging fruits which gave rise to beta-blockers, ACE inhibitors and the statins have long since been plucked from the discovery tree. The genomically identified targets must be “druggable”. Among those that are, expression and purification of the proteins (if that can even be accomplished), the in vitro assay development (including miniaturization), and target validation and characterization for these fruits high in the discovery rain forest canopy are, to be direct, pretty f*cking difficult. And that’s way before we get to looking at potential liabilies of drug metabolism, crossing the blood brain barrier in the case of CNS targetted compounds, pharmacokinetics, and well, a formidable array of issues which stands between lead compound identification and clinical candidate status. Because we discovery primates have to reach that much farther, Wood’s proposals would add a little extra sweetness at the end, or at least something of a safety net to cushion a potential fall.
Wood’s ideas look pretty good to me, but the flies, cf. the Tabanus variety, in the ointment are the FDA itself and the swampy morass that is patent law. Battling these buzzing biting bureaucracies seems quixotic but maybe Dr. Wood will aim a few good swats.
Point: The Truth About Drug Companies by Marcia Angell for the New York Review of Books.
Counterpoint:Of Pills and Profits: In Defense of Big Pharma by Peter Huber for Commentary Magazine.
To paraphrase Mulder, the truth isout there in-between there somewhere.
And just for the hell of it, or maybe because Wood’s recommendation of extended exclusivity might make some squirm, here’s Boldrin and Levine’s case against most any kind of intellectual property. This gives Derek Lowe a headache. I think a headache is a mild way to describe it. I’ll just take a sharpened #2 pencil and ram it into my ear, a la Lewis Black, because that would be more pleasant than no F*CKING IP PROTECTION!