Oncology Biomarker Testing: Why the UK Delay?

May 28, 2014
By Pharmaceutical Executive

Amy Butcher investigates why the UK is lagging significantly behind Europe in the uptake of oncology biomarker testing — and looks at what the delays mean for pharma.


The 1998 launch of breast cancer drug, Herceptin, created a sea change in the treatment of cancer. As one of the world’s first targeted oncology agents, Herceptin uses a biomarker to predict patient response, benefitting thousands of breast cancer patients in the process. Pre-identifying likely responders in this way both increases the efficiency of treatment decisions and reduces unnecessary drug prescribing. As a result, Herceptin’s success changed oncology treatment philosophy; very soon, pharma began channeling its R&D investments into identifying more such targeted therapies.

Today, targeted therapies are used extensively and are expected to make up almost 60% of the global oncology/haematology drugs market by 2017(1). As a result, pharma pipelines are awash with targeted oncology therapies, and the importance of having a marker (or multiple markers) to identify patient response continues to grow.

Against this backdrop, however, our research reveals that the UK is lagging significantly behind its European counterparts in the uptake of oncology biomarker testing…

UK: slow on the uptake
Looking at four different onco-biomarkers over the past eight years — HER2 (breast), KRAS mutation (colorectal), EGFR mutation and ALK rearrangement (non-small cell lung) — it appears that the proportion of relevant patients tested in the UK trails behind that of France, Germany, Italy and Spain. The data show that testing in the UK has been markedly lower than the EU4 average and, more often than not, behind all four markets. At times, the UK’s testing rate was as low as half that of its European neighbors.


What’s more, it seems that this trend is not just a function of slower adoption of the general concept of biomarker testing. Whilst the established biomarkers — HER2, KRAS mutation and EGFR mutation — were ‘first in class’ and introduced when there was little experience in testing, the newer biomarker in NSCLC — ALK rearrangement — shows a similar trend.

So what’s driving this trend in the UK?
Certainly, the most likely explanation is the approval process of the therapy associated with the biomarker. After all, if there is no product available, there is limited value in testing…

NICE — the UK’s National Institute of Health and Care Excellence — is an integral player within the UK’s healthcare system, and has the unenviable task of balancing patient care with stringent and limited budgets. Whilst the NHS’s Cancer Drug Fund has done much to alleviate the pain of delayed and negative NICE decisions, the impact on testing for innovative oncology biomarkers is clear.

Accordingly, the remarkably low UK testing rate in KRAS is no doubt a direct result of the negative NICE recommendation for KRAS-related agents, Erbitux and Vectibix. As before, where no targeted therapy is available for use, there is little value in testing patients. Slower uptake in other tumours can also be attributed to the delay in approval of the related agents.

Ipsos’ research does show that once the related therapy is approved, UK testing rates begin to catch up to the EU average. As familiarity with the procedure grows and access to testing technology is defined, the process becomes more streamlined. In HER2 and EGFR mutation testing, the UK has now caught up with the EU4 (although this has taken years). In other cases such as KRAS mutation testing the UK has only made headway in the last year or so.

It may be the case that other factors are also impacting testing decisions:

· Cost & testing coverage: this varies across the EU, particularly between countries whose healthcare systems are mainly privately financed versus those that are largely publicly funded. Cost constraints in the publicly funded UK system may limit uptake of testing.

· Local / regional / hospital restrictions & guidelines: these may well play a role, leading to different rates of testing even within the UK — relevant given the recent restructuring of the NHS system. There is little in the way of national guidelines for testing and so doctors are led by local standards.

· The testing procedure itself: the integral value of testing lies in the reliability and accuracy of results, in the time taken to return results and, quite simply, in the availability of tests and testing equipment at local laboratories. Indeed, one journal states that up to 30% of labs across the EU were reporting inaccurate results for KRAS testing(2). This may lead to questions over reliability, lower physicians’ confidence and reduce likelihood to test.


So is it all bad news for the UK…?
Not at all. Encouragingly, recent Ipsos Oncology Monitor data (Q1, 2014) shows that once a patient is identified as ‘suitable’ via the testing process, prescribing of the relevant product in the UK is in line with, or ahead of, other EU markets. In the case of mNSCLC, 97% of EGFR mutation-positive patients in the UK were prescribed one of the products indicated specifically in this population – higher than in any other market.

So, once suitable patients are identified, doctors are clearly doing everything in their power to provide the best possible care. The objective is to ensure that the proportion of patients sent for testing reaches EU levels, and that avoidable delays to the testing procedure are limited.

What does delayed testing mean for pharma?
Regardless of the reasons behind the UK’s time lag, the impact on patients, doctors and pharma is significant.

For pharma, there is an inevitable loss of revenue due to delayed prescribing of the targeted product. To compound this, even once the product has been approved hospitals need time to incorporate the required technologies, streamline processes and smooth out any kinks in the testing procedures. In the time taken for testing and the return of test results, doctors are treating their patients with potentially sub-optimal products.

On a more strategic level, a delayed testing process can complicate the decision of which partnering companion diagnostics company to use; if there is a lack of clarity around the standard testing procedures used, pharma may choose a partner that allows for less than optimal coverage in the market.

Finally, there are fundamental issues around marketing strategy and messaging material – vital to the launch of any new product. After all, the most important aspect of marketing is to understand who your main stakeholders are; in the case of a biomarker-led product, identifying the person responsible for the testing decisions is challenging and so messaging concepts become difficult to design.

Looking at the bigger picture, whole strategic marketing campaigns can be put out of kilter if one market (in this case, the UK) is running to a very different timeframe from its neighbors.

The future outlook
The advent of new biomarkers and the growth of personalized therapies does present new challenges for pharma, from changes in the direction of pipelines to the evolution of clinical trial design. The diagnostics field is also changing, with increased regulations and new collaborations between pharmaceutical and diagnostic companies — as well as the emergence of new technologies. But with an oncology product costing an estimated £630m to bring to market, understanding the diagnostics stage is an increasingly important part of the R&D process.

As we’ve established, these strategic decisions are more difficult to make in the UK market, where testing procedures and key stakeholders can be unclear at the time of launch. Looking ahead, unless there is a concerted national shift in attitudes towards testing in the UK (such as we have seen in France, with a government-led aim of blanket oncology biomarker testing), the delay in biomarker uptake is unlikely to change. Only time will tell.

It also remains to be seen whether this will impact innovation in testing in the UK. Will there be a demand for new cutting-edge biomarker and genetic testing technologies — such as next generation sequencing — in a market where use of even the traditional methodologies sees slow adoption?

References
(1) Cowen and Company, Therapeutic Categories Outlook 2012.

(2) Oncologist 2011;16(4):467–78

About the Author
Amy Butcher is Director, Global Oncology Monitor at Ipsos Healthcare.