Developing new drugs is hard. Only a small fraction of chemicals tested in the lab and early patient trials ultimately make it into routine use. Most fall at one of many hurdles on the way – hurdles as diverse as lack of effectiveness, lack of funds, or unexpected side effects.
This hugely frustrating phenomenon is what researchers call the ‘attrition rate’, and is thought to be particularly acute in the complex set of diseases collectively called ‘cancer’.
Estimates vary, but it’s thought that 80 to 95 per cent of potential cancer drugs never make it all the way through the trial system to the clinic.
And when you factor in all the molecules that show promise in the lab but fail to deliver in further experiments or trials, the fraction that make it across this ‘development gap’ between the lab and the pharmacist’s shelf is even lower.
There are many reasons for this, and not all are due to a drug’s biology. Issues of funding, trial recruitment, geography, and bureaucracy all combine with the intrinsic complexity of cancer, resulting in this high attrition rate. In fact, the picture is so complex that entire issues of academic journals have been devoted to discussing it.
But the good news is that, as we announced today, our technology transfer company, Cancer Research Technology (CRT), is teaming up with the European Investment Fund (EIF). Together they’re creating a fund of about £50 million to try to help bridge this gap.
Although this money won’t make cancer any less complex, it will be a much-needed shot in the arm to UK drug developers, and hopefully speed up the rate at which new drugs can be made available to the people that need them.
The development gap
We must never forget that large, rigorous clinical trials, and their ability to methodically pick out what works from what doesn’t, are behind the substantial improvements in cancer survival we see today.
But as an article in the New York Times pointed out last year:
In recent decades, one of the most sobering realities in the field of biomedical research has been the fact that, despite significant increases in funding — as well as extraordinary advances in things like genomics, computerized molecular modeling, and drug screening and synthesization — the number of new treatments for illnesses that make it to market each year has flatlined (pdf) at historically low levels.
At Cancer Research UK we’ve spent a lot of time thinking about ways to plug the leaky ‘pipeline’ that flows from the initial isolation of potential drugs (or drug targets) in the lab – a process our researchers are world leaders at – to cancer drugs used to treat patients.
It’s important for many reasons. We need to make sure we get the most out of every pound our supporters donate. We need to turn the discoveries in our labs into treatments that benefit cancer patients. And we need to help create a climate in which new, innovative lab discoveries can fulfil their potential.
Many factors contribute to the ‘leaky pipeline’, and some are unavoidable (or extremely difficult to overcome).
For example, molecules that are highly active against cells in the lab may not work, or may cause unacceptable toxicity and side effects, in whole organisms.
Equally, animal research is a key (and legally-binding) stepping stone between the Petri dish and the patient. But sometimes differences between species mean a promising drug in mice doesn’t translate into humans.
And then there are differences in genetic makeup between people – sometimes a drug works well in people with certain gene variations, but poorly in people with others.
As we wrote about earlier this month, we’re now discovering that genetic and biological differences inside a tumour may also be why preclinical promise ends in clinical failure.
And finally, side effects or drug resistance can take a while to appear, meaning that a drug that initially looks promising in early trials has to be abandoned at the final hurdle.
But other obstacles can be overcome. And one of the simplest is one facing so many of us in these straitened times – lack of money.
Over the last few years, for a whole variety of reasons (but chiefly to do with the economic climate), the big players in the pharmaceutical industry have focused more on large trials of established drugs – phase III trials – than on early stage discovery.
This means there’s been precious little money around to support small-scale trials to work up promising lab discoveries into drugs for early trials.
Cancer Research Technology’s CEO, Dr Keith Blundy, says this gap is “restraining cancer drug development in the UK”.
“The gap has appeared because investment from industry has moved away from early stage discovery,” he told us. Consequently, there’s less funding for small biotechnology firms who previously helped bridge the gap between academia and pharmaceutical companies.
The money we’re announcing today bridges that gap with an entirely new model of research funding.
Indeed, this is a long term strategic goal of Cancer Research UK’s – joining up the laboratory discoveries of our scientists with the clinical trials carried out by the doctors and clinical researchers we also fund.
The CRT Pioneer Fund
The new fund is the fruit of discussions we’ve had with the European Investment Fund (EIF), which has a remit to invest in projects to stimulate growth and investment across the European Union.
We’ve agreed that CRT will commit £25 million, while the EIF will match this, doubling the Fund’s firepower.
As a result, the CRT Pioneer Fund will be able to fund up to £50 million’s worth of drug discovery research projects, and will commit to fund them all the way up to entry into phase II trials.
At least two-thirds of the fund will be used to develop the most exciting scientific discoveries made by Cancer Research UK scientists. And crucially, these researchers won’t have to set up ‘spin out’ companies – the funds are to be invested in projects, not organisations.
This is, as far as we know, a brand new way of publicly funding drug discovery.
Where will the money come from?
As regular readers may be aware, CRT, our technology transfer company, makes money by licensing lab discoveries to partners in industry (a good example being prostate cancer drug abiraterone). The aim is to invest the resulting royalties back into research.
So the £25 million CRT is investing in the Fund comes out of this revenue.
It is not money donated by our supporters – rather, CRT has taken discoveries made in Cancer Research UK labs (with supporter money), ‘amplified’ it via licensing deals, and then reinvested this back in more research – it’s a genuinely innovative model and a new public pathway for cancer research.
The EIF’s £25 million comes from the European Central Bank, which in turn comes from European governments.
Who decides how it’s spent?
To ensure independence and rigor, the Fund will be governed by a third-party management firm, 6th Element Capital (named after the sixth element of the periodic table, carbon – central to all cancer drugs).
6th Element will appoint a panel of scientific advisors, including Cancer Research UK scientists with international track records in drug development. This will help ensure that the Fund picks winners that are likely to bring benefits to patients, and minimises risks.
Our CEO, Harpal Kumar, said at yesterday’s press conference that the most effective and profitable drugs are ‘scientific’ drugs, where the underlying biology has been rigorously mapped out. “Success comes from letting the science drive things,” he said. This is the principle underlying the CRT Pioneer Fund – matching scientific expertise to a gap in the market, to benefit patients.
David Willetts, the government’s Science Minister, who also attended the press conference, was extremely enthusiastic about the fund. He thinks that it solves ‘a crucial weakness in the UK’s research’.
We certainly hope it will, and look forward to hearing about the fruits of this innovative new partnership to beat cancer.