Xalkori/Zelboraf Approvals: Watching and Waiting - Diaceutics

Xalkori/Zelboraf Approvals: Watching and Waiting

July 6th, 2012

Sanna Jousi

Diaceutics has been monitoring Xalkori/Zelboraf stories as they evolve, tracking the responses and reactions of a number of key stakeholders, such as labs, physicians and payers, to ensure the key lessons to be taken from these two cutting edge approvals are available for future targeted therapy development teams. Sanna Jousi of Diaceutics provides the latest analysis. 

As I’m sure most of you know, the two groundbreaking targeted therapy approvals of last summer, namely Zelboraf and Xalkori, are clear evidence that personalized medicine can shorten approval times and speed drugs to market. Zelboraf and the companion BRAF V600E test were approved ahead of the drug’s October 28, 2011 goal date and the companion diagnostics’ November 12, 2011 goal date. What makes the timing significant is that the FDA PMA review took less than four months when it normally can take between 9 to 18 months. Similarly, Xalkori was also reviewed under the FDA’s priority review program and approved under the accelerated approval program, resulting in the companion diagnostic from Abbott – Vysis ALK FISH – being approved on the very same day.

There is ongoing debate about whether these fast approvals might only reflect successful reorganization within the FDA and a lower workload at the time of these reviews. However, both Roche and Pfizer pursued a number of very similar strategies that helped both companies speed the approval process, including utilizing the modular pre-market approval process and real time adjustments to clinical trials, just to mention a few.

What makes Xalkori and Zelboraf approvals of further interest, of course, is the specific language in the drug labels regarding the tests. For both drugs the Indications and Usage require use of an FDA-approved test. This requirement has certainly caused some frustrations among the laboratories, a story that continues to evolve. Let me give you an example:

Many laboratories have validated BRAF assays with equivalent or even better performance characteristics than the FDA-approved assay. This is a concern among laboratories, as using their own non-FDA-approved test result to the physician to enable Zelboraf prescription might mean that the physician would be considered to be prescribing off-label. The real irony here is that some of the labs that actually helped to develop the test that was used in clinical trials are now expected to discard the test they originally developed in-house and convert to use of the commercial FDA-approved version, which comes with a much higher price tag. The laboratory community is still waiting clear guidance from the FDA and just getting on with the job of testing in the meanwhile, which means that we at Diaceutics will be following this evolving story very closely for quite some time to come.

How are the payers evaluating the two latest targeted therapy approvals?
The large US payers, such as Blue Cross Blue Shield and Aetna, initially adopted testing for Zelboraf and Xalkori fairly rapidly, but were not stringent about which tests had to be used. They emphasized that the FDA-approved tests were only required if “medically necessary” but also noted that other tests could be used, clearly indicating that the payers at least did not immediately dismiss use of LDTs. Whether this was because of their belief in the accuracy of LDTs or the reduced costs is not clear.

However, over the course of the last six months, many payers have moved away from this permissive attitude towards testing. Especially with Zelboraf, many payers have begun to require pre-authorization specifically for use of the FDA-approved BRAF test, in order to obtain a favorable reimbursement decision on the drug.

Diaceutics has been monitoring these two stories as they evolve, tracking responses and reactions of a number of key stakeholders, such as labs, physicians and payers, to ensure the key lessons to be taken from these two cutting edge approvals are available for future targeted therapy development teams. The stories on these two targeted therapies is still evolving and I don’t think we see it settling in any time soon, as both drugs are now moving toward approvals in ex-US markets. Certainly, the market-by-market variation in the ex-US regions introduces an entirely new level of complexity beyond what we have seen in the US to date.

If you are interested in knowing more about Diaceutics’ Market Insights Tracking reports or the complexities of ex-US markets, email info@www.diaceutics.com.


View all blogs

Webinars & Podcasts

August 20th, 2019
Podcast: How Diaceutics is repairing the diagnostic testing ecoystem for patients worldwide
Diaceutics CEO, Peter Keeling joins Pat Kenny on Newstalk FM to discuss how analyzing Big Data to implement better diagnostic testing can help patients access better treatment options for cancer and other life-threatening diseases.
July 5th, 2019
Liquid Biopsy in NSCLC
View all

Expert Insights

April 19th, 2018
The CMS National Coverage Decision on NGS
I. Introduction On March 16, 2018, the Centers for Medicare and Medicaid Services (CMS) finalized a National Coverage Determination (NCD) that cove...
January 19th, 2018
What does the EU IVD Regulation mean for companion diagnostics and LDTs?
Dave Smart, PhD, Director at Diaceutics, discusses the introduction of the EU IVD Regulation. While it is considered a necessary step, the Regulati...
View all expert insights

Competitive Benchmarking Reports

October 21st, 2019
Pharma Precision Medicine Readiness Report 2019
March 16th, 2018
PM Readiness Report 2018 Summary
View all reports

Case Studies

View all case studies


June 25th, 2019
FLT3 testing in relapsed Acute Myeloid Leukemia setting is becoming increasingly common, but laboratory turnaround times (TAT) may be a barrier to treatment with second generation FLT3 inhibitors
The treatment landscape in AML has developed at an astonishing pace in the last 3 years, with 5 therapies being approved by the FDA. FLT3 inhibitors gilteritinib (Gil) and quizartinib (Quiz) present an unprecedented opportunity for improved surviv...
May 23rd, 2019
Diaceutics reviews the ongoing debate on diagnostics reform legislation
Thought leaders at Diaceutics recently authored a peer-reviewed article that covers the ongoing national debate over diagnostics reform legislation in the United States. The article is now available online ahead of print in the Journal of Molecula...
View all publications