Regulatory Affairs & Product Development Services

The Application of Strong Scientific Understanding

Last week a group of 37 leading cancer experts issued a report recommending not to give cancer drugs to patients with terminal cancer just to extend life. This was based on the premise that treatment costs cannot be justified (the UK NHS spends around £5bn annually on cancer treatments). However, campaign groups, such as Bowel Cancer UK, dismissed the report saying ‘’while cancer care can be expensive it is unjust to put a cost on the lives of patients, especially when modern treatments can give them precious time with their loved ones’. Finding the balance between these conflicting positions is difficult.

As a consultant to the pharmaceutical industry, with expertise in cancer drug development, I suggest the solution lies in a completely new approach to cancer drug development – one where a reengineered drug development model and refocused resource would yield greater value for future cancer care. It is true that many cancer drugs currently being prescribed are decades old, have limited efficacy and unpleasant side effects. Even the most effective modern drugs extend life expectancy by only a few weeks, and although each extra day spent with loved ones is precious, those extra days are almost always marked by unpleasant toxicities, discomfort and pain, without any quality of life enhancements. Billions of pounds each year are spent to find cures for cancer, and success stories are rare. Improvements in reduced deaths from breast cancer have been largely due to better diagnosis and surgery, rather than in new drug treatments per se. The industry has not found a cure for cancer. Researchers and developers need to do better. A new approach is required.

First, there has been a standard approach to cancer drug development, which has not changed for decades. Large companies still continue to follow these approaches, and implement the same strategies as another. Unsurprisingly repeating failed approaches results in continued failure. Clinical trials usually have quality of life markers as tertiary end points, let alone primary end points. Trials are simply not designed with quality of life measures as the primary goal. Second, the main industry metric is ‘time’. In the rush to register new treatments, drug development is so often conducted at the expense of quality. Many drugs show promising efficacy in Phase 2 clinical trials, yet the primary endpoint (usually overall survival rate or time-to-progression) in the Phase 3 registration study fails with the result that potentially promising medicines are not registered. Why? I believe companies do not stop to think long enough about their promising Phase 2 data, with the result that factors such as dose level selection, optimizing dosing intervals in combination studies, strategies to reduce toxicities, manufacturing formulation development studies, and examinations in subpopulations in which greater efficacy exists, are not fully examined. Many potential new drugs are not approved for one or more of these reasons. Phase 2 data which would result in valuable insights are overlooked, and poor decisions are rapidly carried forward to the Phase 3 programme. Third, patients recruited into pivotal clinical trials usually have terminal, late-stage disease. Even if a drug regimen could be made to work, it is often ‘too little too late’. The industry has not stopped to think. If effect, companies are ‘’rushing to fail’’.

Cancer drug development needs a new approach. Phase 2 development needs to be much more extensive. Multiple dose ranging studies should be conducted which examine a wider range and combination of dose levels, dosing intervals and dose route strategies. Different sub-populations should be more fully examined (including biomarker and genotype studies). Crucially studies should be conducted in earlier stage disease with a complete overhaul in inclusion and exclusion criteria relevant for these trials, as well as validating new clinical endpoints for these cohorts. This strategy must also be accompanied by simultaneously putting more resource into early diagnosis and prevention so that suitable patients can be identified earlier. These approaches will require the introduction of new guidelines and Directives, as well as a change in the profile of expertise required by both Industry and regulatory assessors. Such an approach would also pave the way for the introduction of innovative technologies such as gene therapy, immunotherapy and stem cell approaches into the mainstream Pharma industry, rather than big Pharma waiting on the sidelines of ill-funded academia to drive innovation. It is difficult to change the tide of many years of repeated behaviour of a global industry. But the changing landscape of funding assessments, touched on in the 37 cancer experts report, and the rebuttal of campaign and patient groups, indicates that a change is necessary. The risk of not changing the approach to cancer drug development is surely greater than the risk of not doing so. 

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