In the News
Jun 01, 2009
Biomarker testing in cancer treatment is a driving influence in the larger trend of increasing specialization – raising the likelihood that patients will benefit from treatment they receive and, in turn, improving perceptions of drug efficacy. The interesting long-term effect: positive perception influenced by a smaller population will ultimately increase use of a drug even beyond the highly defined patient population.
The market strategy of targeting small to grow large, proven with Herceptin and the HER2 biomarker test, is naturally accelerated by giving the test away for free, or similar strategies to encourage testing.
The managed-care community is responding. In April 2009, UnitedHealth Group made the decision to base coverage for Erbitux and Vectibix on KRAS test results. This follows a study announced at the ASCO 2009 Gastrointestinal Cancer Symposium, predicting more than $600 million annually can be saved by the healthcare system if Erbitux use is directed by KRAS testing.
It's no surprise that the managed-care community embraces the concept of specialized chemotherapy. Payers gain assurances that therapies are more likely to be effective, and expensive drugs are given to smaller populations. Yet short-term cost concessions are eventually lost as reinforced positive perception gives way to expanded use.
Ultimately, pharmaceutical and payer stakeholders share the same long-term goals in oncology: ensuring the right drug is used in the right patient – exemplified in the decision to design clinical trials and limit reimbursement based on wild-type KRAS test results. Both sides, however, must closely assess the market impact of these decisions. Today, it's not correctly done and, unfortunately, lands pharmaceutical teams and managed-care policymakers at opposite ends of the spectrum.
Payer assessments often take the short-term view on something that requires long-term vision. Pharmaceutical companies commonly look longer term. Both parties need an accurate measurement of the market opportunities that will be affected by these clinical decisions, and they need to track the historical and future impact.
In the late 1990's Genentech Inc.'s Herceptin showed targeted use in the HER2+ patient population would provide breast cancer patients with significant clinical benefit. The efficacy of Herceptin in the HER2+ population drove earlier adoption of the product, multiple use of the product, adoption as a maintenance therapy, and longer durations on therapy. Genentech's early strategy was to provide physicians with access to the appropriate diagnostic tests to ensure they were testing for HER2 status, increasing the likelihood that patients would receive Herceptin.
Today, even though only 20% to 25% of newly diagnosed breast cancer patients are HER2+, almost 35% of treated breast cancer patients receive Herceptin driven by maintenance use. The KRAS decision might affect the colorectal cancer market in a similar manner. In 2008, multiple studies showed that colorectal cancer patients whose tumors have mutated KRAS genes do not benefit from treatment with epidermal growth factor receptor inhibitors such as Erbitux and Vectibix.
Prior to KRAS clinical data, IntrinsiQ believed that oncologists were quickly evaluating patient response to EGFR therapies and non-responders were more likely to discontinue early. As one might expect, these non-responders were disproportionally mutant KRAS.
Today, about 25% of third-line-plus colorectal cancer patients receive Erbitux, a costly drug proven to extend durations of response and time to disease progression in this patient population. More consistent KRAS screening will likely eliminate the "trial" use of Erbitux, where it's unlikely to be effective. Yet the long-term trend is likely to take a different turn.
Clinical data suggests that about 60% of patients are wild-type KRAS and 40% of patients might be mutant KRAS. Through KRAS screening and reimbursement pressures from the managed-care community, EGFR therapy will likely become unavailable to the mutant KRAS patient population, which more likely represents less than 20% of existing EGFR sales. Clinical data that appeared in 2008 removed a sizeable share of the "excess" cost to the healthcare system, in a short-term cost benefit.
Incremental cost savings will likely accelerate after implementation of KRAS screening mandate decisions, but with effective product positioning, costs will likely increase over the long term. This is caused by a reinforcement of the positive messages of the product in a patient population that is more likely to respond.
Although only 60% of patients might qualify as wild-type KRAS, marketers of EGFR therapies can regain majority control of this market. Providing the tools necessary to test for KRAS and delivering positive messages on the product's benefit in the qualifying patient population could result in market share vastly exceeding its current usage in the third-line-plus market.
Pharmaceutical companies should view this as ensuring their therapy is used in the right patient and the right tumor at the right time, and effective strategic market research could reinforce the product's positioning. Pharmaceutical companies will also try to move the KRAS test closer to diagnosis, in case the patient relapses.
Yet payers would like the physician to test patients when a decision to use an EGFR arises, typically in latter lines of therapy. The winning strategy will have tremendous impact on the amount of Erbitux and Vectibix used in colorectal cancer.
The war on cancer has been part of our collective consciousness since 1971, and we have seen some massive shifts in the oncology market. Today, cancer is not a single disease, but hundreds of specific tumors that require specialized approaches to effectively treat the patient. Ten years ago, there were significantly fewer drugs that were marketed to specific tumors. Now we're looking at smaller patient populations that could benefit with the right product. The opportunity hasn't diminished, but the strategy is far more varied and complex.
Editor's note: This is one of an occasional series of guest columns. Ed Kissel is VP of quantitative analysis for IntrinsiQ, a source for U.S. oncology data and analysis.