Take your seats, investors: The battle in first-line advanced renal cell carcinoma, the most common type of kidney cancer, is about to begin.
In one corner, weighing in at a market cap of $8 billion, there's Exelixis (NASDAQ: EXEL) and its tyrosine kinase inhibitor Cabometyx. In the other corner, towering over the smaller biotech with a market cap of $103 billion, Bristol-Myers Squibb (NYSE: BMY) packs a one-two punch with its immuno-oncology drugs Opdivo and Yervoy. It's a David versus Goliath battle, but David is holding his own so far with sales of Cabometyx coming in at $80.9 million in the second quarter.
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This is round two of the companies' ongoing battle that started in second-line kidney cancer, where Exelixis' Cabometyx and Bristol-Myers' Opdivo both trounced the defending champion, Afinitor, sold by Novartis (NYSE: NVS).
Rather than throwing punches at each other, the companies showed off their skills by air boxing. In first-line kidney cancer, they again tested their respective drugs against the current champion, Pfizer's (NYSE: PFE) Sutent, which is the right thing to do to gain approval, but without a head-to-head trial comparing the drugs, it's difficult to make any strong conclusions.
Adding to the complications comparing the drugs, neither trial against Sutent went exactly as planned.
Cabosun, Exelixis' trial testing Cabometyx against Sutent, wasn't designed to be used for regulatory approval. The scans to measure tumor progression were assessed by the individual investigators in the trial rather than by a centralized review committee, which the FDA likes to see because it's likely to be more consistent. But since the data was quite striking, showing that Cabometyx delayed the progression of the tumor growth while keeping patients alive -- called progression-free survival (PFS) -- Exelixis decided to use Cabosun to try and gain approval as a first-line treatment.
To check all the boxes and make the FDA happy, Exelixis sent all the tumor scans to an independent radiology review committee, which confirmed the investor-assessed data, concluding that Cabometyx improved PFS compared to Sutent. Cabometyx also improved overall survival, but because the trial wasn't set up to be used for approval, the difference wasn't statistically significant.
CheckMate-214, Bristol-Myers' trial testing Opdivo and Yervoy against Pfizer's Sutent, also didn't go exactly as planned. Last month the company said the trial met one of its co-primary endpoints: Opdivo and Yervoy improved the objective response rate -- which measures whether a tumor responds (shrinks) -- compared to Sutent. But the trial failed to show that the combination improved PFS, one of the other co-primary endpoints, by a statistically significant margin.
The company let the trial continue to look at a third co-primary endpoint, overall survival, and the trial was stopped early because the independent data monitoring committee concluded that Opdivo and Yervoy improved overall survival.
Here's what the data looks like for the two treatments in comparison to Pfizer's Sutent. As you can see, the control groups responded substantially differently to Sutent, likely because Exelixis enrolled more advanced patients, making comparing the two data sets difficult.
While the difference in median overall survival can't be compared because less than half of the patients taking Opdivo and Yervoy have died, it's also possible to compare survival with something called a hazard ratio, which compares the rate of death over time. Using that measurement, Cabometyx reduced the risk of death by 20% compared to Sutent, while Opdivo and Yervoy reduced the risk of death by 37%.
On the surface it looks like Opdivo plus Yervoy beats Cabometyx since patients care more about living longer than they do about how quickly their tumors start growing again, but it's hard to make strong conclusions given how differently the control groups responded.
It should also be noted that Exelixis has a head start on Bristol-Myers Squibb, having submitted the Cabosun data to the FDA as well as to European regulators through its partner Ipsen. Cabometyx was also recently listed in the National Comprehensive Cancer Network (NCCN) guidelines as a first-line treatment for kidney cancer. Many insurers use NCCN as a guide for what to pay for, giving Exelixis an additional head start. And as fellow Fool Keith Speights points out, Cabometyx may also be priced lower than Bristol-Myers combo, giving it an additional leg up with insurers.
Can't we all just get along?
While the battle between Exelixis and Bristol-Myers for first-line patients makes for good entertainment, hopefully it won't last too long. The companies are testing Cabometyx and Opdivo with and without Yervoy compared to Pfizer's Sutent in a phase 3 trial called CheckMate 9ER.
The trial will measure PFS as the primary endpoint, so it won't take as long to run as a trial measuring overall survival. Nevertheless, the companies plan to enroll over 1,000 patients in the trial, and then enough of them need to progress before the data can be analyzed. The companies listed February 2021 as the end of data collection, although hopefully investors will have an answer earlier if there's a clear difference in the combination treatments over Sutent.
In the meantime, whichever company doesn't prevail in the first-line battle for patients will still have plenty of patients to treat as a second-line treatment since neither Cabometyx nor Opdivo plus Yervoy are cures.
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