December 2012, Vol 1, No 6

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Companion Diagnostics and the Paradoxical Return of the Blockbuster Drug

Robert Emmett Henry

The Last Word

In my article in the inaugural issue of Personalized Medicine in Oncology, I got a bit dogmatic in proclaiming that personalized medicine (PM) drug treatment selectivity spelled the end of population-based medicine, and with it, the blockbuster drug. This is true only insofar as we define blockbuster drug from within the population-based drug utilization process that PM is replacing. As PM establishes itself, a new kind of blockbuster drug is emerging with a criterion that supersedes its predecessor. Since blockbusters have sustained the pharmaceutical industry for decades, concern about the demise of the blockbuster drug has been strong: if PM and its reliance on biologicals in cancer care is incompatible with blockbuster drugs, could this spell the collapse of the pharmaceutical/biologicals industry? The question is worth answering. PM, after all, must be more than a Pandora’s box of unintended consequences.

The new blockbuster drug model is form-fitted to PM dynamics. The old blockbuster model required massive, population-based drug utilization. If randomized controlled trials showed positive results, the drug would find indiscriminate use in practice and payer coverage just as indiscriminate – almost an urge to “put it in the tap water,” especially when it went generic. PM alters that, of course, aligning drugs to patients based on body chemistry, not empirical averages. This is an enriched population, and it is guided, even empowered, by companion diagnostics, to shrink patient populations to boutique levels. This only redefines, not eliminates, blockbuster drugs, by achieving targeted value propositions. Blockbuster drugs provide the profits needed for the technologically ambitious research for biologicals. The new targeted model accommodates this need, which augurs well for a robust pipeline of quality drugs supportive of the PM cancer care revolution. It may turn the blockbuster drug model on its head, but it achieves the same results: stabilization of the healthcare system and affordable cancer treatment.

The old blockbuster rules of engagement entailed expanding utilization to the furthest limits of credibility, courting off-label usage, and blindly searching to bring the drug to the right patient through a massive process of elimination. The process was tolerated because companion diagnostics technology did not exist. Now that it does, drug utilization can be limited to an enriched patient population based on individual patient chemistry. Last year the FDA got radical and simultaneously approved 2 drugs with companion diagnostics. One was Roche’s vemurafenib, for patients with metastatic or inoperable melanoma with tumors testing positive for the BRAF V600E mutation, with its companion diagnostic, the Roche cobas 4800 BRAF V600 Mutation Test. The other was Pfizer’s crizotinib, approved for late-stage non–small cell lung cancer, and Abbott’s Vysis ALK Break Apart FISH Probe Kit, for detecting abnormal anaplastic lymphoma kinase (ALK) gene expression.

These simultaneous approvals signal the dawn of this new era of the minibuster, increasing drug effectiveness while facilitating payer coverage. Now pharma can go with the flow of PM’s smaller patient populations and still end up with a blockbuster, only now its financial success is based on value, not volume. Never has “less is more” meant more to every stakeholder in the process of care. Results, not waste usage, now form the basis for blockbuster drug status. This can allow for a rational pricing and utilization strategy, helping cancer care stay on the high road where it belongs. Diagnostics pave the way for drug utilization based on clinical merit, not dubious patient selection methods. It allows pharma to achieve its financial goals while remaining true to its clinical mission.

The selectivity of biologicals usage will see high unit costs, but it is attractive to payers who recoil at the prospect of an onslaught of aging baby boomers receiving unsustainable levels of biologics. This is making diagnostics as valued as the drugs they measure, since they keep biologics affordable by cutting waste – and not just in clinical treatment, but also in research. The average cost of a new drug launch hovers near $2 billion, a problem aggravated by research failures. Companion diagnostics not only lessen payer worries over waste drug usage, they also help fast-failure research, which will allow biologicals to be priced more affordably.

Dan Theodorescu, MD, PhD, Paul Bunn Professor of Cancer Research, professor of urology and pharmacology, and director of the University of Colorado Comprehensive Cancer Center, described the process: “Developing drugs is so expensive that the industry can’t afford any longer to take a drug to phase 1 or 2 clinical trials and find out that it’s not working like they hoped. It’s clear that the biomarker or markers should be embedded in the process very early. In my opinion, even phase 1 trials should be biomarker-driven for patient selection and prediction of response.” He predicts that pharma will pursue the companion diagnostics approach, relying on this fast-fail approach to identify winning products worth taking to phase 2 and beyond. Pharma can afford the small patient populations it previously could not afford to attend to because payers will tolerate a higher price tag for a drug with a higher likelihood of clinical success.

The role of companion diagnostics in the new blockbuster model demonstrates the intricacy of PM and the interlocking stakeholder relationships that sustain it. The blockbuster drug has been retooled in boutique proportions to fulfill the PM quest for targeted, predictable, low-waste usage. This will attract investors, whose funding has never been more critically needed, at this young stage of research into biomarkers and other methods for predicting biologicals’ clinical utility. Pharma will have to master this transition, titrating the price-to-treatment ratio to balance their financial needs with those of patients and payers. Breakthrough biologicals usage is now being sustained by equally remarkable companion diagnostics. Together they make possible a flourishing of value: the elusive balance of cost, quality, and access that brings the process of care from theory into practice.

To Our Health,

Robert E. Henry

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