Who will take up the gauntlet?

In 2002, the Editorial that accompanied the launch of Nature Reviews Drug Discovery stated that “[d]espite all the excitement that accompanies each wave of technical innovation, from protein structure determination to proteomics, and from combinatorial chemistry to e-clinical trials, the fundamental truth is that pharmaceutical companies are not producing drugs any faster than they were before these innovations came along” (Anon, 2002). A subsequent Editorial written on the occasion of the fifth anniversary of the journal asked whether the industry was in a better state than it had been 5 years previously, and concluded that the answer was a “resounding no” (Anon, 2007). In the intervening period, Leroy Hood and Roger Perlmutter had already predicted that the pharmaceutical industry would lose ~US$80 billion in revenue by 2008, and stated that the current approaches to drug discovery and development could not keep up with demand (Hood & Perlmutter, 2004). This article now seems to have been prophetic: in a valedictory article published in the Harvard Business Review in 2008, Jean-Pierre Garnier, former chief executive officer of GlaxoSmithKline, pointed out that between December 2000 and February 2008, the industry lost ~US$850 billion in shareholder value, with a concomitant decline in share prices from an average of 32 times earnings to 13 times earnings (Garnier, 2008). During the past 10 years, the cost of bringing a single new drug to market has escalated hugely to somewhere in the region of US$1 billion; however, the success in doing so has approximately halved compared with the early 1990s, and the time taken has doubled to ~12 years, although efforts are succeeding in reducing this to some extent. Industry statistics show an increased productivity in recent years in delivering candidate drugs from discovery into development; however, this has not been matched by success in the clinic, and there have been several well-publicized failures of drugs in the later stages of development (Anon, 2004, 2007; Frantz, 2007). This indicates that, although the output of projects from discovery into development has increased, the quality of the output has not. Responding to this situation by simply playing the ‘numbers game’—increasing the number of projects and speed of delivery through the pipeline in the hope of increasing the chances of hitting a successful outcome—would be similar to continually pumping more fuel into an inefficient engine just to maintain its output. Alternative approaches need to be considered to tackle this problem.