Biomarkers and oncology forecasting: How to hit a ... - Kantar Health

Biomarkers and oncology forecasting: How to hit a moving targetPeter MansellStaff WriterPeter Mansell - Aug 3, 2010Peter Mansell investigates why biomarkers and other molecular diagnostic tools may bethe most undervalued area in oncologyMuch of the current boom in the oncology market can be attributed to the emergence of more targetedproducts that use biomarkers and molecular diagnostics to hone efficacy and limit side effects in betterdefinedpatient populations.At best, this is a win-win situation for companies, physicians, patients, and healthcare systems—the righttreatment for the right patient at the right dose at the right time.It is especially important in a climate in which cost-effectiveness and predictability are increasingly thearbiters of drug choice and uptake, even in a category that historically has been spared this level ofscrutiny.Another consequence of the shift towards personalized medicine in oncology is to add layers ofcomplexity to a market in which forecasting is already muddied by issues such as multiple therapyregimens, health technology assessment, pressure for more flexible pricing and reimbursement models,wavering political status, and diminishing elbow room around key indications.More and more, oncology forecasting will need to take biomarkers into account, which means multiplyingthe assumptions and scenarios that feed into assessments of individual product potential.The significance of biomarkersThe significance of biomarkers extends far beyond their ability to segment markets by tailoring therapy tothe responsive patients.They are also intrinsic to streamlining research and development so that new treatments can be broughtto market more quickly, more efficiently, and at a lower cost.

2Despite the availability of high-profile targeted anticancers such as Gleevec (imatinib) or Herceptin(trastuzumab), drug development in oncology “remains painfully slow,” note Eric Groves, Jason Hill, andChristopher Ung of Quintiles in a recent white paper.Only 8% of new molecular entities in oncology make it to market and late-stage failures are common, withapproximately six out of ten drugs in development falling by the wayside in Phase III trials.Stripping out some of that risk calls for tools that can elucidate a drug’s mechanism of action and steerselection of the most appropriate patients to enrich the clinical study population, mitigate risks to nonresponders,and facilitate earlier assessment of efficacy.As the Quintiles executives point out, over the past two decades molecular biomarkers have “becomeestablished components of clinical research in a way few could have foreseen.”At the same time, this rapid evolution is reshaping clinical practice and the oncology marketplace.“Now a particular tumor type is no longer classified by its histological properties alone,” Groves, Hill, andUng comment.Biomarkers are increasingly used to segment tumor types by molecular profile.“So, for example, breast cancer is now recognized as containing luminal A, luminal B, basal type, erbB2,and triple negative sub-populations, each of which have a different management strategy, and vary inpatient prognoses and therapy response characteristics.”The end result is that marketed oncology products “live in an environment where the market’s size (targetpopulation) is continually being affected by evolving patient selection biomarkers, and these effects on thepotential use and sales of a drug can be large,” the white paper authors add.The most undervalued area in oncologyKarol Sikora, medical director of CancerPartnersUK, sees biomarkers and other molecular diagnostics asthe most undervalued area in a category heading for meltdown under the competing pressures of costcontainment, ageing populations, earlier intervention, an explosion of new and expensive therapies, moreaggressive patient expectations and advocacy, and hard questions about the real value of incrementalsurvival benefits. (For more on forecasting challenges, see ‘Forecasting for complex diseases’.)These tools can radically alter the cost-effectiveness ratio for cancer therapies and, in doing so, addressstakeholders concerns across the board, Sikora believes.By 2020, Sikora foresees at worst risk prediction in small patient subsets and at best population riskbanding for cancer.Micro-bands will reclassify cancers by targeting specific disease pathways.There could even be routine molecular phenotyping before prescribing decisions are taken.That means overhauling pharmaceutical industry strategy in the category, Sikora told eyeforpharma’srecent Oncology Market Access Europe 2010 Summit in London.Biomarkers and oncology forecasting: How to hit a moving target, eyeforpharma

3In the 1990s, it was all about being first in class, achieving market leadership with one or two indications,and spinning it out through lifestyle management.The next 10 years will require a “more subtle” approach, with companion diagnostics segmenting themarket and driving new line extensions, Sikora predicted.As things stand, the pool of oncology products with associated biomarkers is still “relatively small” interms of patient numbers, notes Dr Robert Ramsey, vice president and chief scientific officer of KantarHealth.Where biomarkers have become part of standard care, though, such as in breast or colorectal cancer, theimpact is substantial.And in a comparatively minor indication like chronic myelogenous leukemia, the effect of targeting therapyat the BCR/ABL biomarker (Gleevec) has been to extend lifespans from around six months to six orseven years, Ramsey points out.Moreover, most of the emphasis in oncology drug development is now moving away from what Ramseycalls the “blunderbuss” approach towards more tailored therapies.Targeted biomarkers include mutations of the B-RAF gene (melanoma and colorectal cancer), of EML4-ALK (non-small cell lung cancer), FLT-3 (acute myeloid leukaemia) and BRAC 1/2 (variety of tumours).(For more on the related area of biosimilars, see ‘Forecasting the future of biosimilars’.)Biomarker developmentTo date, though, biomarker development has generally been “hit and miss,” Ramsey acknowledges.“We don’t know enough about the biology of these drugs and what they’re affecting early on in clinicaldevelopment to know where we should look for biomarkers.”If a drug is targeted at a genetic mutation, it should be detectable, he adds.But with biomarkers such as HER2 (Herceptin) or oestrogen receptors (tamoxifen, aromatase inhibitors),“We’re not aiming just at a mutation, we’re looking at some other aberration in terms of metabolism.”As Ramsey explains, a biomarker such as HER2 provides a measurement along a continuum, rather thana simple yes/no answer—as with K-RAS (Erbitux) or EGFR (Iressa) mutations.Consequently, there needs to be cut-off points indicating a positive result, and so far these have been set“arbitrarily.”Even with a yes/no biomarker, where the objective is to determine the presence or absence of mutations,there are complications.For example, Ramsey notes, tumors are by nature heterogeneous.So if a biomarker test yields a positive mutation, that raises the question of what proportion of cells in thetumor a positive measure actually represents.Biomarkers and oncology forecasting: How to hit a moving target, eyeforpharma