10 February 2011

Innovation in Drug Development: An Inverse Moore's Law?

Today's FT has this interesting graph and an accompanying story, showing a sort of inverse Moore's Law of drug development.  Over almost 60 years the number of new drugs developed per unit of investment has declined in a fairly constant manner, and some drug companies are now slashing their R&D budgets.

One question is why this trend has occurred.  The FT points to a combination of low-hanging fruit that has been plucked and increasing costs of drug development.
To some observers, that reflects the end of the mid to late 20th century golden era for drug discovery, when first-generation medicines such as antibiotics and beta-blockers to treat high blood pressure transformed healthcare. At the same time, regulatory demands to prove safety and efficacy have grown firmer. The result is larger and more costly clinical trials, and high failure rates for experimental drugs.
Others point to flawed innovation policies in industry and governments:
“The markets treat drug companies as though research and development spending destroys value,” says Jack Scannell, an analyst at Bernstein Research. “People have stopped distinguishing the good from the bad. All those which performed well returned cash to shareholders. Unless the industry can articulate what the problem is, I don’t expect that to change.”

Mr [Andrew] Baum [of Morgan Stanley] argues that the solution for drug companies is to share the risks of research with others. That means reducing in-house investment in research, and instead partnering and licensing experimental medicines from smaller companies after some of the early failures have been eliminated.

Chas Bountra of Oxford university calls for a more radical partnership combining industry and academic research. “What we are trying to do is just too difficult,” he says. “No one organisation can do it, so we have to pool resources and expertise.” He suggests removing intellectual property rights until a drug is in mid-stage testing in humans, which would make academics more willing to co-operate because they could publish their results freely. The sharing of data would enable companies to avoid duplicating work.

Patrick Vallance, senior vice-president for discovery at GSK, is cautious about deferring patents until so late, arguing that drug companies need to be able to protect their intellectual property in order to fund expensive late-stage development. But he too is experimenting with ways to co-operate more closely with academics over longer periods.

He is also championing the “externalisation” of the company’s pipeline, with biotech and university partners accounting for half the total. GSK has earmarked £50m to support fledgling British companies, many “wrapped around” the group’s sites. One such example is Convergence, a spin-out from a GSK lab researching pain relief.

The challenge is for academia and biotech companies to fill the research gap. Mr Ratcliffe argues that after a lull in 2009 and 2010, private capital is returning to the sector – as demonstrated by a particular buzz at JPMorgan’s new year biotech conference in California.
The Wall Street Journal points to different approaches to and understandings of the role of innovation in drug development:
Big pharmaceutical companies are scrambling to find ways to overcome the loss of tens of billions of dollars in revenue as patents on top-selling drugs run out. Many sound similar notes about encouraging entrepreneurialism in their ranks, making smart deals and capitalizing on emerging-market growth, But their actual plans are often quite different—and each carries significant risks.

Novartis AG, for instance, is so convinced that diversification is the best course that the company has a considerable business selling low-priced generics. Meantime, Bristol-Myers Squibb Co. has decided to concentrate on innovative medicines, shedding so many nonpharmaceutical units that it' has become midsize. GlaxoSmithKline PLC is still investing in research, but like Pfizer it has narrowed the range of disease areas in which it's seeking new treatments.

Underlying the divergence is a deep-seated philosophical dispute over the merits of the heavy investment that companies must make to discover new drugs. By most estimates, bringing a new molecule to market costs drug makers more than $1 billion. Industry officials have been engaged in a vigorous debate over whether the investment is worth it, or whether they should leave it to others whose work they can acquire or license after a demonstration of strong potential.
To what extent can approached to innovation influence the trend line in the graph above?  I don't think that anyone really knows the answer.  The different approaches being taken by Merck and Pfizer, for instance, represent a real world policy experiment:
The contrast between Merck and Pfizer reflects the very different personal approaches of their CEOs. An accountant by training, Mr. Read has held various business positions during a three-decade career at Pfizer. The 57-year-old cited torcetrapib, a cholesterol medicine that the company spent more than $800 million developing but then pulled due to safety concerns, as an example of the kind of wasteful spending Pfizer would avoid.

"We're going to have metrics," Mr. Read said. He wants Pfizer to stop "always investing on hope rather than strong signals and the quality of the science, the quality of the medicine."

Mr. Frazier, 56, a Harvard-educated lawyer who joined Merck in 1994 from private practice, said the company was sticking by its own troubled heart drug, vorapaxar. Mr. Frazier said he wanted to see all of the data from the trials before rushing to judgment. "We believe in the innovation approach," he said.
The outcomes will be worth following.