Dx Launch Risks
This case study shows how a risk management strategy for possible recalls could prevent disruption, not only to a biomarker's market progress, but to ...
Diaceutics gave a presentation at TriCON 2017 discussing how biomarkers and diagnostics are still falling short at launch, even though the industry is no longer in its infancy. Here, Jordan Clark, Managing Director, reports on how we can track the real-time, real world development of PD-L1 in NSCLC and highlights the differences in the test’s availability, budgeting and resourcing.
The dynamic PD-L1 space provides opportunities to undertake real-time market analysis and improve our understanding of novel biomarker adoption. It’s an interesting space, too, seeing as in the first 18 months since launch over 70 US labs are using the test, indicating PD-L1 testing has a fast-track pattern of uptake in parallel with treatment recommendations. It’s also in line with ALK and EGFRm – 75% of all NSCLC trials for five PD-1/PD-L1 therapies are likely to require known PD-L1 status, bringing PD-L1 in line with ALK and EGFRm as key disease-based biomarkers. When we combine these facts with the knowledge that the anti PD-1 therapy class of drugs is slated to achieve $33 billion, it is worrying that the PD-L1 testing market is still underdeveloped.
There is an increasing interdependency between therapy and diagnostic that is likely to continue as regulatory authorities around the world encourage joint submissions for approval and support simultaneous launches. In the US we observe that:
PD-L1 testing is a dynamic market that has given Diaceutics a unique opportunity to analyse the availability and adoption of PD-L1 in NSCLC as a real-time, real world example. What we mean by availability is having nearby, trusted laboratories to run the chosen test. Analysis of the PD-L1 market reveals that in less than three years there have been three new entities, six indications, over 16 approvals and more than three tests, and this list was expanded in March 2017 with the approval of Keytruda for cHL and Bevencio for Mercel cell carcinoma.
Within NSCLC, PD-L1 status reveals a competitive component given that around 40 per cent of all NSCLC trials, regardless of the phase (I-IV), require determination of PD-L1 status. However, despite therapy/diagnostic dependency and expected PD-L1 integration, barriers to availability and adoption persist. This is a concern because we know that unaddressed diagnostic need leads ultimately to the loss of potential patients eligible for targeted therapy.
What are the factors affecting availability in the US?
Various factors can affect availability including confusion over testing options, interpretation and reporting of results. Our analysis of PD-L1 testing in the US reveals these are some of the questions raised:
Another factor affecting availability here is the significant role LDTs play in the provision of PD-L1 testing. Around 50% of labs have only an LDT option, but LDTs are less well-defined with the Ab being used and cut-off values in place. Often labs will offer both LDT and kits but there is no suggestion that LDTs are preferred.
Even though availability of PD-L1 testing has increased since companion diagnostic approval it has always lagged behind. Diaceutics began tracking PD-L1 testing in 2015 and found that test availability already lagged behind 2014 approvals. 2016 saw strong availability of PD-L1 testing but we may also have reached a testing plateau at the end of 2016 in the US, with broad adoption in key laboratories.
Does Europe experience similar issues on availability?
The Diaceutics global network of laboratories has enabled us to track particular markets in relation to PD-L1 testing and a focus on Germany and Italy for PD-L1 in NSCLC has provided some contrasting data on availability and investment in these countries3.
|Comparison of PD-L1 testing in practice||Germany||Italy|
|Top volume NSCLC laboratories performing PD-L1 testing||93%||8%|
|All NSCLC samples tested for PD-L1||44%||2%|
How do availability issues impact physicians?
We recognise that availability and adoption – the adoption of the test by physicians for use with recommended patients (as described in guidelines) – can be interdependent. The test needs to be available in labs to facilitate physicians’ choice on testing but if they adopt a particular test above others the availability of other tests can be reduced. Understanding around test differences is improving but prescribers remain unclear and this creates uncertainty for prescribers and impacts their confidence in testing4. Furthermore, pharma companies are sending out different messages, with the 22C3 companion diagnostic being promoted with Keytruda and 28-8 complementary diagnostics promoted with Opdivo.
How do availability issues impact testing and ROI?
The availability issues clearly impact return on investment and timely investment will boost the returns. When Diaceutics analysed the differences between the German and Italian markets for the webinar What are the major differences in biomarker test adoption in European countries? An analysis of PD–L1 testing in Italy and Germany, it revealed surprising statistics about Italy in relation to PD-L1 testing:
This one example demonstrates that despite prescribing’s increasing dependency on PD-L1 testing, issues of availability and adoption persist. Crucially, 20 years on from Herceptin we still observe the absence of attention to pre-launch market development for critical biomarkers and patients are being missed. (More information will be made available after our bottom up analysis of patients lost to anti PD-1 treatment directly caused by testing issues is completed in May 2017.)
An increasing requisite for PD-L1 status knowledge prior to prescribing will drive increased outcomes and response rates with PD-L1 therapies but guidelines clarifying PD-L1 testing and reporting are lagging behind the dynamic testing landscape. Several factors however, including early physician confusion and a lack of standardization in testing and reporting, will continue to hinder test availability. A comprehensive biomarker strategy is key to a successful therapeutic launch and increasingly impacts return on investment but current planning and implementation on the majority of biomarkers is underestimated, under-budgeted and under-resourced
1. Diaceutics’ Pharma Readiness for Diagnostic Integration 2017
2. FDA Review Process for Companion Diagnostic Devices (Soma Ghosh, Tri-Con presentation 2017)
3. Diaceutics webinar February 2017, What are the major differences in biomarker test adoption in European countries? An analysis of PD–L1 testing in Italy and Germany
4. Diaceutics’ Longitudinal Panel of PD-L1 Testing Behaviour Among Prescribers. (This panel leverages an analysis of the same 20 Opdivo/Keytruda prescribers in NSCLC to track shifting perceptions over time.)