April 19th, 2018
The CMS National Coverage Decision on NGS
New Insights: As a result of the recent CMS National Coverage Decision on NGS, the MolDX® program of Palmetto GBA® is now actively considering cover...
Herceptin is a HER2/neu receptor antagonist indicated for:
CHICAGO — The breast cancer drug Herceptin is considered the model for the future of medicine tailored to each individual. The drug is given only to the 20 percent of breast cancer patients whose tumors have a particular genetic characteristic.
But now, nearly a decade after the drug’s approval, evidence is emerging that the testing of the tumors can be highly inaccurate or that the wrong cutoff values are being used to determine who qualifies for treatment.
That could mean that as many as 40 percent of women with early breast cancer might benefit from the drug but are not getting it, some experts say. Yet other women may be paying for the drug and risking its side effects unnecessarily.
Dr. Pamela M. Klein, an executive at Genentech, the manufacturer of Herceptin, said the company was continuing to explore how to best identify patients for the drug.
“Here we are, 10 years into it,” said Dr. Marc L. Citron, an oncologist in Lake Success, N.Y., “and we don’t know how to test for it.”
Herceptin's enormous success as a targeted therapy is well known. But examining its story in detail provides valuable insights into the evolution of today's personalized medicine market.
1999 - HercepTest (IHC): approved same day as Herceptin (1998)
2002 - Vysis Pathvision FISH test approved and added to Herceptin label
2005 - DakoCytomation Her2 FISH pharmaDx test approved
2008 - Genetic Test by Invitrogen called the SPOT-Light HER2 CISH Kit approved by FDA
2010 - Two molecular tests launched for breast and gastric cancer
Herceptin is financially and clinically successful, proving personalized medicines can generate blockbuster sales.
However, Genentech, the company that developed Herceptin, took a long time to take charge of and drive the companion diagnostic market.
A lack of coordinated market development for Herceptin testing caused diagnostic issues.
|Aspect of Dx Implementation||% of Physicians Surveyed Experiencing Problems 2006|
|Storage and sending of samples||20% and 60% respectively|
|Communications with lab||53%|
|Limited testing capacity||47%|
|Interpretation of results||20%|
To avoid implementation problems with the test, it is necessary to take 'ownership' and optimize the development of the diagnostic market.
A late start on development of the diagnostic also contributed to Herceptin’s implementation problems.
|Signal stability||Archivable||Fades over time||Archivable|
|CProtocol length||Overnight + 3hr, 55min||Overnight + 3hr, 12min||3hr, 2min|
|Amount of training required||Medium||High||Low|
|Interpretation||Objective / Quantitative||Objective / Quantitative||Subjective / Qualitative|
|Market adoption by oncologists in 2008||1-2%||20-40%||100%|
The adoption of the Herceptin platforms varies significantly.
Inferior technologies are often more widely used than superior ones introduced later.
Even a decade after HercepTest, the National Comprehensive Cancer Network (NCCN) believes it is necessary to include special instructions around HER2 testing quality.
Multiple testing and retest steps are required to identify patients for Herceptin.
Even in 2005, the majority of HER2 testing is still relying on the IHC method and up to 20 to 60 per cent variability in sensitivity is reported in HER2 studies. This serves to undermine physicians' confidence in the test answer.
Overall P2P rates remain high, despite testing confidence, as Herceptin is regarded as the only therapy in the HER2 class. Tykerb is eventually launched by GSK in 2008 but does not make a significant impact on Herceptin P2P levels.
Doctors' lack of confidence in the accuracy of companion diagnostic tests for Herceptin had a direct impact on their willingness to prescribe it.
Propensity to prescribe (or the ratio of therapy prescriptions written to test positive outcomes) is not automatic and needs to be earned.
Propensity to prescribe cannot be assumed to be the same for each indication of the therapy.
Herceptin is a very successful personalized medicine product, but its sales could have been significantly higher with better diagnostic market preparation.
Diaceutics estimates that Genentech's lack of an upfront investment of $10-20m, needed to drive test adoption and standardize the companion diagnostic, has potentially cost between $2-3bn in lost revenue in the US alone.
We can consider Genentech’s initial Herceptin Dx strategy (years 1-5) as suffering from a series of critical leaks.
These leaks have been the focus of Roche investment since 2005 in an effort to improve the ROI for Herceptin.
A pharma company with an Rx asset dependent on a test should take a proactive approach to managing the Dx environment from the outset, in order to drive adoption and avoid implementation flaws.
Physicians can be put off using a promising new targeted therapy if the Dx environment is not a straightforward exercise optimized to suit their needs.
A suboptimal Dx environment can cause substantial financial losses to an Rx asset.
There are several potential areas of considerable 'leakage' in any Dx environment. This leakage can result in the loss of patients demanding testing (for a drug that depends on such a Dx environment) and in the population indicated for testing by guidelines.
Understand the current Dx routine at the physician's office.
Understand propensity to prescribe (P2P) in terms of your plan.
Prepare and revise your Dx strategy.
Prepare for a Dx technology evolution.