International – Immuno-Oncology: What’s Next for Pharma?

Immuno-oncology has significant diagnostic needs, including identifying patients most likely to respond to therapies. Current diagnostic approaches often fall short, due in large part to the complexity of the biology driving therapy responsiveness. As such, the biopharma industry is exploring many emerging approaches covering tumor, immune and even microbiome-related pathways and biomarkers.

Immuno-oncology represents a paradigm shift in cancer treatment, with the first wave of PD-1/PD-L1 checkpoint inhibitors such as Opdivo (nivolumab, from Bristol-Myers Squibb Co.) and Keytruda (Merck & Co. Inc.’s pembrolizumab) demonstrating cure-like performance in selected metastatic tumors such as nonsmall cell lung cancer (NSCLC) and melanoma.

This efficacy is driving significant checkpoint inhibitor adoption, and analysts project the class alone could represent a $29 billion global market by 2022. In short, checkpoint inhibitors are providing hope to metastatic patients who were previously considered to be on a path to palliative care.

Despite their performance, checkpoint therapies have a number of shortcomings. For instance, response rates are still only 20 to 30% on average (although there is significant variance in published response rates by tumor type), and response times can be prolonged, which can be an issue for patients with advanced metastatic disease.

Checkpoint inhibitors also come with significant side effects, especially when used in the combination regimens (e.g., with anti-CTLA-4) that are ubiquitous in the industry. (Also see “Combinations Continue to Drive Immuno-Oncology DealMaking,” In Vivo, May 2017.) Checkpoint inhibitors’ cost (at up to $150,000 per year for monotherapy) represents a significant burden to healthcare systems and payers. Furthermore, prior exposure to checkpoint therapy may render patients ineligible for other immune-oncology clinical trials.

Today, PD-1/PD-L1 immunohistochemistry tests (IHCs) are available as companion or complementary diagnostics for many approved indications, yet their predictive power is considered limited in many situations. As such, while these IHCs are broadly ordered by clinicians, decisions to use checkpoint therapy may often be based on lack of therapeutic alternatives coupled with substantial patient demand. This is creating significant need for improved diagnostics to predict response to checkpoint therapy, to monitor response and to support sustained usage…