• Better-than-expected positive results from a late-stage study could position Merck & Co’s immunotherapy Keytruda to play a large role in the treatment of metastatic kidney cancer, putting pressure on rival Bristol-Myers Squibb at a critical time.
• Combining Keytruda with Pfizer’s Inlyta nearly halved the risk of death in previously untreated patients with metastatic renal cell carcinoma (RCC) when compared to Pfizer’s older drug Sutent, currently the standard of care. Notably, the combination’s benefit was consistent across risk groups and levels of PD-L1, a biomarker frequently correlated with response to immunotherapy. 
• While Merck has largely wrested a leading position in the immuno-oncology market from Bristol-Myers, RCC is one cancer type Bristol-Myers’ rival Opdivo still holds a marked advantage in, having secured approvals in 2015 and 2018. Analysts view Merck’s data as highly competitive, however, and likely to position Keytruda well versus Opdivo.

The renal cell carcinoma market looks to become newly competitive following trial successes from Merck and, earlier, Pfizer. 

While immuno-oncology approvals have proliferated in recent years, to date Bristol-Myers’ Opdivo (nivolumab) is the only PD-1/PD-L1 inhibitor to hold U.S. approvals in RCC — an advantage that has helped sustain the franchise as Merck’s Keytruda (pembrolizumab) has gained ground in lung cancer. 

Opdivo is OK’d both as monotherapy for second-line RCC and, more recently, in combination with Yervoy (ipilimumab) in the frontline setting for intermediate- or poor-risk patients. Bristol-Myers has quickly capitalized on that second approval and, as of the third quarter, staked a roughly 30% to 35% share of the first-line RCC market. 

That position now looks to be under threat. Following positive data announced last fall, Pfizer announced Monday that it’s secured priority review from the Food and Drug Administration for its combination of Bavencio (avelumab) and Inlyta (axitinib). A decision on approval is expected by June.

Merck, though, may yet take a pole position in what’s estimated to be the third largest immuno-oncology market behind lung cancer and melanoma. 

Results disclosed Monday in a study abstract ahead of this year’s Genitourinary Cancers Symposium showed Keytruda plus Inlyta to drive a powerful survival benefit over Sutent, reducing the risk of death by 47%. 

At one year, 89% of patients given the combination were alive versus 78% of those treated with Sutent. 

Treatment-related adverse events rated grades three through five were common, affecting 63% of patients on the combination and 58% on monotherapy. Only 6% of patients in the Keytruda arm discontinued their treatment regimen, however, compared to 10% on Sutent.

The results compare favorably to the data shown by Bristol-Myers in its CheckMate-214 study, which led to the first-line approval of Opdivo plus Yervoy in RCC.

“Key competitor Bristol-Myers has been gaining share in the 1L RCC market with their Opdivo + Yervoy combo but Merck’s data appears superior given a lower [overall survival hazard ratio], a positive impact on [progression-free survival] and an impact being seen across a broader population,” wrote Credit Suisse analyst Vamil Divan in a note to investors. 

A number of questions still have to be answered, however. Full data from Merck’s study won’t be available until a Saturday presentation at the Genitourinary Cancers Symposium, so it is not yet known what proportion of patients in the trial were PD-L1 positive — a factor that could influence comparisons to Bristol-Myers’ results. 

Merck’s survival data is also only through 12 months, shorter than what Bristol-Myers has read out for Opdivo plus Yervoy. 

“An 18-month evaluation of [Merck’s study] will be important to determine if survival rates for Keytruda + Inlyta continue to be stronger than Opdivo + Yervoy, or if patient deterioration drives the OS HR to be closer to that seen in CM-214,” wrote Cowen analyst Steve Scala in an investor note. 

For its part, Bristol-Myers has acknowledged that it expects the RCC market to become more fragmented. But it’s also touted what it judges to be more durable responses spurred by Opdivo and Yervoy, as well as the experience its salesforce has gained in introducing immunotherapy to RCC physicians. 

The pharma also has an ongoing study of Opdivo plus Exelixis’ Cabometyx (cabozanitinib), a drug that works similarly to Inlyta. Results from that trial are expected later this year.

Shares in Merck rose by more than 2% in Tuesday morning trading, while Bristol-Myers opened down slightly.