Three of the world's biggest pharmaceutical companies have signed a landmark deal with the UK government that will see them use stem cell technology to road-test the safety of new compounds.
Stem Cells for Safer Medicines (SC4SM ), a not-for-profit company, has been founded by a public-private consortium headed by the Department of Health and the Association of the British Pharmaceutical Industry and is being supported by a host of significant research players, as well as three pharmaceutical companies, AstraZeneca, GlaxoSmithKline (GSK) and Roche. Each are believed to have committed an initial £100,000 to the project, and a spokesperson for the ABPI said in an interview that a total of £1m (€1.44m) is in the pot for the first year. The entire five-year programme is expected to cost in the region of £10m.
The idea is that the stem cell tests can take place before the drugs enter animal studies, ultimately helping to improve the attrition rate of pharma's R&D pipeline.
The parties were keen to stress that they will not be looking into the therapeutic potential of stem cells themselves, but instead will "establish open standards and techniques for how stem cells may be used for medicines safety testing" and will "share discoveries to enable consistency in this pre-competitive research".
The primary focus will be on differentiating liver cells from existing stem cell lines, the liver being one of the body's most complex organs and responsible for drug and toxin metabolism.
More predictability in compound screening
Stem cell technology will allow for much more predictability in terms of screening out compounds that will be toxic to the liver, noted the spokesperson, adding that "currently it's not much better than tossing a coin". By building such liver testing into screening programmes, pharma could ultimately clean up its compound libraries and have greater assurance that medicines will last the distance through to market and beyond. It could also, therefore, have a positive impact on pharma's relatively high attrition rate in later-stage development.
Certainly, the pharmaceutical industry has more than a passing interest in ramping up the safety of its medicines, with liver toxicity having been the primary cause of some major product withdrawals and late-stage failures over the past few years. The most recent case is Novartis' COX-2 inhibitor Prexige (lumiracoxib) which was pulled from the Australian market, given stronger restrictions in Europe, and awarded a 'not-approvable' letter from the US Food and Drug Administration (FDA) as a result of its potential adverse impact on the liver.
AstraZeneca has also been affected, last year reeling its clotbuster Exanta (ximelagatran) from the global marketplace after new patient safety data threw up a single case of serious liver injury. It had originally been touted as a $3-$4bn (€2.1-€2.8bn) product.
Clearly, any technique that could lessen the risk of drug R&D is likely to receive the full support of the pharmaceutical industry. "It's going to become more and more interesting to pharma as it starts to see the potential applications of this technology to its compounds," the spokesperson asserted. Indeed, next on the list is the differentiation of heart cells, with cardiotoxicity being the second principal reason for drugs failing in development or being pulled from the market.
The SC4SM is currently in talks with a number of other pharmaceutical companies about their potential involvement and is "pretty confident" it will be able to sign others up. This is the first time that the pharmaceutical industry has been directly involved in the contentious area of human embryonic cells, so establishing this consortium has somewhat sensitive. However, Philip Wright, science director at the ABPI and chief executive of SC4SM, says that the ethical guidelines state it is restricted to using stem cell lines already in existence in the UK stem cell bank. An independent ethics advisory board will come into force at the beginning of next year to provide further advice and guidance.