Article by Peter Lang and Naval Shanware
Few cancer therapeutics have engendered as much enthusiasm, and generated as much hype, as the new generation of cancer immunotherapy or immuno-oncology (IO) agents. Key among these IO therapies are the checkpoint inhibitors (hereafter simply referred to as IO). Since the approval of Yervoy (anti-CTLA-4) for melanoma about six years ago, IO agents have steadily altered the oncology treatment landscape and disrupted the standard of care.
IO’s appeal is obvious: approvals have been driven by breakthrough clinical efficacy, manageable tolerability, and the induction of incredibly durable responses in thousands of patients with metastatic cancers. The past three years have been particularly impactful with the approval of five anti-PD-1/L1 antibodies (Opdivo, Keytruda, Tecentriq, Imfinzi, and Bavencio), in 10-plus tumor types (in addition to Keytruda’s approval in MSI-high patients, irrespective of tumor of origin). Unsurprisingly, substantial commercial success has followed, and in 2017, the market leaders Opdivo and Keytruda brought in blockbuster revenues of $4.9 billion and $3.8 billion, respectively. As a result, IO therapies are marching on, and our recent analysis identified 50-plus IO pivotal trials alone, with peak sales moving toward an impressive ~$28 billion by 2025.
This come-from-nowhere success of IO has been a tremendous boon for patients, but it also has caused substantial consternation at the R&D organizations of biotech and pharma. The success of Opdivo and Keytruda, and to an extent Tecentriq, split pharma into "IO-haves" and "IO-have nots," leaving oncology-focused companies to answer several key strategic questions:
While much has been written on these topics elsewhere, this article focuses on the equally important but somewhat less well-addressed questions regarding non-IO therapies, and their future in the oncology market. Our clients in biotech and Big Pharma continue to wrestle with defining the optimal balance between IO/non-IO agents in the pipeline and are continually grappling with optimal positioning and co-positioning (with IO) of their non-IO assets. Key among the non-IO assets are the targeted therapies (TTs), defined here as non-chemotherapy, small-molecule inhibitors, or monoclonal antibodies that are directly tumor-targeted, as compared to the immune system-targeted IO agents. Despite the understandable excitement about IO, it is important to remember that in 2017 alone, of the nearly 35 oncology approvals for novel agents/therapies, 20 were TTs. Therefore, managing non-IO portfolios continues to be a strong strategic imperative for all oncology-focused companies.
Retrospective analyses can often provide useful insights to guide future strategy. As such, IO-impacted markets, especially those with TT competitors, represent useful case studies to answer the questions raised above. The melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) markets have all seen substantial IO-mediated disruption of their otherwise TT-driven markets. Importantly, we also have 24-plus months of commercial, on-market experience in the U.S. market, post-IO entry, in each of these tumor types, providing us with a substantial "lookback" period to inform our analysis.