After the market close on 9/24 BMY announced that in an interim analysis its CM274 Ph3 trial, evaluating Opdivo vs. placebo in the adjuvant setting (after surgery) in patients with high-risk, muscle-invasive urothelial carcinoma (MIUC, a type of bladder cancer) met the primary endpoint of disease-free survival for patients regardless of PD-L1 expression levels, as well as in the subset of patients with PD-L1 expression >1%. We view this as a positive on multiple fronts for Opdivo - both for the outlook within adjuvant MIUC, particularly after the failure of ROG’s Tecentriq in a similar Ph3 trial earlier this year (link), and for the I/O outlook within the adjuvant setting more broadly given that this follows its recent positive data in adjuvant gastroesophageal cancers (topline announced last month and full data presented at ESMO). BMY has two additional near-term adjuvant readouts upcoming: and neo-adjuvant NSCLC (CM-816; pCR data in 2H20/EFS data in 2022) and adjuvant melanoma (CM-915, combo with Yervoy in 2H20). We model $870mn in Opdivo unrisk adjusted revenue for the adjuvant bladder, which we risk adjust by 60%. We note there may be upside to this estimate given the positive Ph3 data and the fact that we had assumed Tecentriq would capture a portion of the market as well (see our deep dive on the adjuvant opportunity here). Across the major neo/adjuvant indications we model $1.5bn/$920mn unadjusted/risk adjusted 2025E sales for Opdivo.
CM274 evaluated Opdivo vs. placebo in the adjuvant setting in patients (N=700) with high risk MIUC. The trial was broadly similar to ROG’s IMvigor010 Ph3 trial on size, primary/key secondary endpoints, and exclusion criteria, with the only difference being the comparator arm (placebo in CM274, observation in IMvigor010). Per the BMY release the safety profile was consistent with previous Opdivo studies in solid tumors. The trial will continue to allow for future analyses of secondary endpoints, including OS and disease-specific survival. BMY plans to present the full results at an upcoming medical conference and submit the data to regulators. Bladder cancer can be divided into a number of subtypes (urothelial carcinoma, squamous cell carcinoma, adenocarcinoma). Urothelial carcinoma (UCC) is the most common bladder cancer and accounts for ~90% of cases. Bladder cancer can also be described by non-invasive (small and easily removed), non-muscle invasive (spread to bladder wall, but not muscle) or muscle-invasive (spread to muscle). Keytruda (2017), Opdivo (2017), Imfinzi (2017) and Tecentriq (2016) are approved for the second-line treatment of metastatic urothelial carcinoma following chemo, while only Keytruda (2018) and Tecentriq (2017) are approved for front-line treatment. Growth for I/O drugs within bladder cancer will come primarily from expansion to the adjuvant setting. The current standard of care for non-metastatic urothelial cancer is surgical resection accompanied by (neo)adjuvant chemo in some cases, and survival rates for invasive tumors that have not spread outside the bladder remain ~70%. Given success in the metastatic setting, use of PD-(L)1 therapy in the (neo)adjuvant setting has the potential to improve survival rates among stage II/III bladder cancer. For non-metastatic muscle invasive bladder cancer, we previously estimated a potential US+EU5 opportunity of $1.1-$3.4bn in the neoadjuvant/adjuvant setting, assuming 25-75% treatment rates (see Exhibit 26 here). Per Roche there are ~17.4k/~32.8k MIBC cancer patients eligible for neo/adjuvant therapy. We assume an annual treatment cost of $150k/$104k in the US/EU5 (10% GTN adjustment) with an average treatment duration of ~2.6 months and 12 months for the neoadjuvant and adjuvant settings, respectively.