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Out of Order: If you build it …
September 2012
by Randall C. Willis  |  Email the author

It seems that every year, the song is the same, and more often than not, the opening refrains appear with an English accent.
In June, the United Kingdom's National Institute for Health and Clinical Excellence (NICE) rejected reimbursement of Roche's melanoma drug Zelboraf not because it didn't work, but because they didn't show it made enough of a difference in overall survival to warrant its premium price over existing therapies.
Explaining the decision at the time, NICE's CEO said, "We need to be sure that new treatments provide sufficient benefits to patients to justify the significant cost the NHS is being asked to pay. [Zelboraf] is an expensive drug and its long-term benefits are difficult to quantify."
Last December, Novartis faced a similar issue when NICE rejected reimbursement for its multiple sclerosis treatment Gilenya. Again, Dillon argued, "While Novartis submitted evidence that shows Gilenya can reduce relapses, our independent committee has not been convinced that it is a cost-effective treatment option, even with the proposed Patient Access Scheme."
In both cases, of course, the companies argued that NICE was wrong in their interpretations of the impact of these drugs on patient populations. Fine, NICE isn't very nice when it comes to getting expensive drugs to market in the U.K. Nothing new under the sun. Similar pressures are felt by drug companies in countries throughout Europe and in Canada, and they are increasingly feeling the pressure from payors within the United States.
So why do I bring this up now?
Because, as I begin research for two upcoming feature articles on personalized medicine (which will appear in our October and November issues), I realize that the current challenges to convince payors to … well, pay, will likely escalate as pharmaceutical firms develop a wider array of drugs designed to more effectively and safely treat smaller and smaller patient communities.
The math speaks for itself. If the cost of developing the drug doesn't change (or at least not appreciably), but it is being delivered to fewer patients, then the cost of treatment per patient will need to be higher to recoup the investment. This is something payors aren't happy to hear as they face tightening budgets and expanding patient rolls.
And Zelboraf is something of a poster-boy for this challenge. Touted by some as the prime example of personalized medicine at work, Zelboraf is targeted at a specific subset of metastatic melanoma patients who share a common genetic profile (positive for the V600E mutation of B-Raf), and was co-developed with a diagnostic test (also from Roche) to identify patients with this biomarker. Despite its clear efficacy in clinical trials, however, NICE expressed concern over the uncertainty of long-term survival benefits as many patients in the trial switched treatment as their disease progressed, something that happens commonly in cancer trials when one arm is shown to be particularly effective.
In this case, it seems that Roche did everything that has been asked of them in the co-development of a targeted therapy with a diagnostic test to ensure only those patients most likely to benefit would receive treatment, and yet they are left scratching their heads, while patients are left with what some might now consider suboptimal treatment options.
And this discussion is being held over treatment of patients with a marker that occurs in a large percentage of the metastatic melanoma population. What does the future hold for Vertex Pharmaceuticals ' Kalydeco, approved in January as a treatment for a rare form of cystic fibrosis (carrying the G551D mutation) that occurs in only 4 percent of CF patients (about 1200 patients)?
Where companies traditionally have had to jump through hoops to impress regulators to approve the drugs they develop, they will increasingly find themselves jumping through even narrower hoops to convince payors that they have made significant strides in improving patient care.
From a business perspective, that will mean paying even closer attention to identifying the drug targets most likely to produce not just safe and effective treatments, but safe and cost-effective treatments. It will mean rethinking the clinical trial process to ensure that the numbers look as good as possible—not just better—when compared to current standards of care, which will rely on finding those patient subpopulations as early as possible. And it may even mean repeating clinical trials once a select patient population has been identified as achieving a particularly outstanding benefit.
Ironically, we may inadvertently increase the costs of drug development while trying to ensure cost-effectiveness of the drugs that finally make it to patients. For the sake of payors, I hope the money they save today by refusing payment will help offset some of the potential excesses later.
And for the pharmaceutical companies, the lesson might be: If you build it, they will come … but they won't necessarily pay for it, so build wisely.
Willis is the features editor of ddn. He has worked at both ends of the pharmaceutical industry, from basic research to marketing, and has written about biomedical science for almost two decades.
EDITOR'S NOTE: We have recently been informed that the NICE guidance regarding Zelboraf was not a final guidance, but rather a first-draft decision. The final guidance is not expected to be published before December, according to NICE. Similarly, the Gilenya discussion was centered on a first-draft decision, and in its final guidance, NICE recommended Gilenya for use by the NHS. We regret any confusion we may have caused, and thank officials at NICE for the clarification.



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