A combination featuring Exelixis’ experimental drug zanzalintinib has beaten Bayer’s gastrointestinal cancer med Stivarga in a phase 3 trial. The overall survival win moves Exelixis a step closer to its ambition of turning the oral tyrosine kinase inhibitor into a $5 billion-a-year product.
Exelixis is developing zanzalintinib as the successor to its flagship oncology medicine Cabometyx. By improving attributes including pharmacokinetic half-life, the company has designed a molecule that it believes can win approval in a range of diseases and blast past Cabometyx’s peak sales. The phase 3 colorectal cancer trial was a key early proving ground for zanzalintinib.
Investigators randomized 901 patients to receive Stivarga or zanzalintinib in combination with Roche’s checkpoint inhibitor Tecentriq. Overall survival in previously treated non-microsatellite instability-high metastatic colorectal cancer was significantly longer on the combination than on Stivarga.
William Blair analysts said in a note to investors that the hit on the trial’s co-primary endpoint ensures a “meaningful commercial opportunity for the budding franchise.” The patient population covered by the endpoint represents the largest commercial opportunity open to zanzalintinib, according to analysts, who estimated risk-adjusted U.S. peak sales of $875 million.
The analysts will be looking out for relative and absolute risk reduction when the full results are shared, because “these metrics could help us ascertain the clinical meaningfulness of the survival benefit.” But the available results are positive, leading investors to send Exelixis’ share price up 12% to about $45 on Monday.
Exelixis will, however, need to rack up more clinical wins to deliver its major vision for zanzalintinib. The biotech expects GI cancers, including colorectal tumors, to account for 45% of the $5 billion in sales it hopes to generate in 2033. GI cancers accounted for 10% of Cabometyx sales last year, making the indications central to Exelixis’ ambitions to improve on the $1.8 billion generated by its current product.
The biotech’s pursuit of the phase 3 colorectal cancer population could put it in competition with drugs including Amgen’s Lumakras, Bayer’s Stivarga, Taiho Oncology’s Lonsurf and Takeda’s Fruzaqla.