(Source: Pharmafile 2015-03-09）
The global system for discovering new cancer drugs is broken. It is failing to turn dramatic scientific advances into enough innovative, game-changing medicines for people with cancer – and it is failing to deliver new drugs at an affordable cost for taxpayers.
Soon, one in two people in the UK will get cancer and so better treatments are urgently needed and innovation is essential to achieve this. Although around 500 cancer-causing proteins are known, we only have drugs that target about 5% of them – and so it is essential to focus more effort on discovering innovative drugs that act on currently untargeted cancer proteins.
I believe we need radical changes in the approaches taken by the whole of the life sciences sector to discover and develop new cancer drugs. Without these changes, we will see major opportunities to address areas of unmet need in cancer missed, and companies falling behind as they continue to focus on drugs which bring only incremental benefits.
It will only be possible for companies to meet the challenges ahead if they receive more support from governments – and form more partnerships with the universities and research institutes who are best placed to shoulder the risk of prioritising innovative, unproven areas of research.
Risk and innovation
I recently gave the keynote lecture at the World Oncology Forum in Switzerland, a gathering of 50 global leaders in cancer research. One of the arguments I put forward there was that pharmaceutical companies are not sufficiently incentivised to take the risks they need to create innovative and exciting treatments that work in new ways.
I have often said that many companies are too focussed on developing me-too drugs which bring incremental benefits to patients. But clinical trials are hugely expensive, so companies are unwilling to invest in ‘risky’ unprecedented drugs which might not be successful.
A consensus statement I signed along with many others from the World Oncology Forum – presented at Januarys World Economic Forum in Davos – calls for governments to incentivise companies to take greater risks in drug development, encouraging them to produce innovative new drugs that deliver big steps forward in survival, and speeding up progress towards long-term control and cures for cancer.
Cheaper, faster trials
I think we do need governments to provide more incentives for drug companies – but not through higher prices, which are unsustainable. One of the suggested practical measures I’ve put forward – along with others from the World Oncology Forum – is to increase the number of innovative medicines coming through the pipeline by bringing in a more flexible drug authorisation system.
The most promising, innovative cancer drugs should be licensed earlier, without needing extensive data from expensive large-scale trials. Companies could also do much more to bring down the sky-high costs of clinical development, by employing advances in genetics and the use of biomarkers to design smaller, more targeted trials.
And authorisation bodies must be prepared to license drugs on the basis of trials of just a hundred or so patients, rather than the several hundreds or more commonly required in Phase III trials – where the evidence of therapeutic promise supports this.
A more streamlined system of clinical trials could speed up progress against cancer, reduce companies’ costs and deliver faster access to new drugs for patients.
In return, pharmaceutical companies should cut the initial prices of cancer drugs to reflect their lower development costs – but they should also be allowed to raise prices for the best drugs once evidence builds that they have major benefits for patients.
For all this to happen I think we must have a more transparent system for agreeing prices. Our World Oncology Forum consensus statement argues that governments should ensure the amount they pay for drugs reflects the size of the benefit they deliver – and that is not possible at present because of a lack of transparency in the process for price setting.
Incentives to innovate
As another encouragement for pharmaceutical companies to take more risks in their drug development, we could offer further incentives for those that work in partnership with universities and charities on innovative projects.
Together, they could share the risks, costs and of course the benefits of drug discovery and development. That could be done through tax breaks for companies that work in partnership with universities or charities to share risk, or extensions to the periods of market exclusivity granted as part of drug patents.
The World Oncology Forum also made the case for giving more tax credits for research and development to companies which invest in treatments for rare and childhood cancers – where it is less profitable to develop drugs – and for which there is very clear unmet need.
And drug companies need to know that when they have invested in an innovative drug development programme and created a medicine that delivers real improvements in outcomes, they will have the opportunity to take it to patients.
In the UK, it is essential that NICE and the Cancer Drugs Fund take into account how innovative a medicine is when considering whether to make it available on the NHS.
The way forward
I believe these measures could begin to fix our failing ecosystem of drug discovery and development, and focus it less on me-too drugs and more on genuinely innovative drugs that could meet areas of unmet need.
We need a vibrant and innovative pharmaceutical sector, because the scientific challenges we face remain profound. There is still not enough being done to overcome the single biggest obstacle to successful treatment of cancer – drug resistance, driven by tumour evolution.
This is a major focus of research here at The Institute of Cancer Research, especially in our new Centre for Evolution and Cancer. We are also aiming to meet the challenge of cancer evolution and drug resistance by identifying and implementing the best drug combinations, and by discovering new ‘cancer network’ drugs that hit multiple targets.
Drugs used in combination could together give greater benefits to patients than the sum of their parts. To overcome drug resistance, we will need to use those combinations – as in HIV and tuberculosis – to cut off cancer’s evolutionary escape routes.
The Institute of Cancer Research will be conducting a programme of research to scientifically select the most effective drug combinations, for evaluation in clinical trials.
Network drugs tackle more than one of the cellular signalling pathways that are hijacked in cancer. These drugs can hit cancer harder than drugs targeted to only one protein, because they can act on several targets at once.
One example is the experimental drug AUY922, which targets a chaperone protein called Hsp90 and was discovered by our researchers in collaboration with industry partners.
It is now showing promise in clinical trials against drug-resistant cancers, and there is new evidence that Hsp90 inhibitors can block the process of evolution to resistance for both hormonal agents and kinase inhibitors.
We need to be looking beyond the low-hanging fruit when it comes to drug discovery, and to focus our efforts on more novel drug targets to produce really innovative drugs that tackle major unmet needs in cancer.
I see our broken model of drug discovery and development as the biggest challenge in our efforts to get exciting and game-changing new drugs to patients.
Earlier access to new medicines is what everyone wants – researchers, doctors, pharmaceutical companies and patients.
Until we fix the system, we will not produce enough of the really innovative cancer treatments that patients expect and deserve.
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