Historically, breast cancer has set the scene for pharmaceutical success stories, supporting the rise of several blockbuster drugs through its large, biomarker-defined subpopulations and long treatment durations. However, while the breast cancer market currently continues to fuel rapid sales growth of key drugs, this may not be the case in the future. A trend in the drug development pipeline to further segment subpopulations could challenge the sales potential of novel breast cancer drugs.
- Historically, segmentation of the breast cancer market into well-defined patient populations based on HER2 and hormone receptor (HR) status has facilitated lucrative sales for key drugs.
- Originally approved for HER2-positive breast cancer in 1998, in 2015 Roche/Genentech/Chugai’s Herceptin commanded over $6 billion in sales worldwide, the majority of which were accounted for by this indication. Prior to patent expiry, Novartis/Chugai’s Femara and AstraZeneca’s Arimidex, both approved for HR-positive breast cancer, also garnered high sales in the indication.
- Sales of Roche/Genentech/Chugai’s Perjeta for HER2-positive breast cancer (first launched in 2012) tipped over the $1B mark in 2015. Pfizer’s Ibrance, which launched in early 2015 for HR-positive, HER2-negative disease, has shown impressive sales growth in the indication, booking almost $700 million in just 11 months.
Positioning new market entrants into increasingly discrete and targeted sub-populations may facilitate better patient outcomes, support drug approval, and drive favorable reimbursement. In light of these potential benefits, many agents in the breast cancer pipeline are looking to carve out a niche by aligning themselves with new biomarkers. For example, several PARP inhibitors are positioning themselves in late-stage trials for the 5-10% of breast cancer patients carrying BRCA1/2 mutations, and Roche has positioned its Phase III PI3K inhibitor taselisib in HR-positive patients who are also PIK3CA mutation positive. Another example comes from Medivation/Astellas Pharma’s Xtandi, which has selected androgen-receptor-positive breast cancers in its Phase II trials.
Existing breast cancer subpopulations may be more (or less) susceptible to further biomarker segmentation than others. Triple-negative breast cancers, defined only by their lack of HER2 and HR-expression, are a prime target for biomarker segmentation owing to their inherent heterogeneity. The HR-positive, HER2-negative population is also an attractive target for the development of novel biomarkers for different reasons; in this large population, patients are often eligible for multiple lines of therapy, and the few available branded therapies in this population mean there is little competitor marketing to contend with. Conversely, no late-stage therapies are currently looking to further segment the HER2-positive population, where the blockbusters Herceptin and Perjeta are approved. Robust efficacy achievements of available HER2-targeted agents and Roche’s established stronghold in this sub-population may be among the factors currently discouraging developers in this space.
Despite the fact that biomarkers have so far helped to drive commercial successes in breast cancer, further segmentation could erode the opportunity for novel drugs to achieve blockbuster status. The introduction of new, smaller segments within pre-existing biomarker sub-populations would reduce the number of patients eligible for a given drug, and therefore restrict the sales opportunity of individual therapies. Approved drugs with broad subpopulation approvals could also suffer as their eligible population is divided and conquered by novel agents by virtue of their additional biomarkers. While this is unlikely to limit overall market growth, it would see average revenue contribution from individual breast cancer therapies decrease. In this scenario, it will be only the best in class agents strongly linked to a biomarker predictive of therapeutic benefits that will reap commercial rewards. Larger biomarker-defined populations will remain lucrative (as they are now), but perhaps only until a further, novel biomarker is introduced.