- Roche's climb to catch its rivals in immuno-oncology became a little steeper Thursday, when the Swiss pharma reported Phase 3 trial results that showed combining its checkpoint inhibitor Tecentriq with another drug failed to improve survival in patients with colon cancer.
- The study, called IMblaze 370, pitted Tecentriq paired with a MEK blocker called Cotellic against Bayer's Stivarga in second- or third-line colorectal cancer that had advanced locally or become metastatic.
- Shares in U.S. biotech Exelixis, which originally developed Cotellic and earns a cut of the drug's profits from Roche, fell by nearly 10% on the news. The companies are also testing the drug combination in two studies of patients with certain types of advanced melanoma.
Among the five PD-1/L1 inhibitors now approved in the U.S., only Merck & Co.'s Keytruda (pembrolizumab) and Bristol-Myers Squibb's Opdivo (nivolumab) carry approvals in colorectal cancer (CRC).
Both, however, are OK'd for use specifically in CRC patients with tumors that are characterized by a genetic condition known as microsatellite instability (MSI) or are deficient in DNA mismatch repair. That limited patient population means CRC currently is not a large market for either drug — analysts from Cowen estimate the indication accounted for only $135 million in sales in 2016.
Roche's study, however, tested whether adding Cotellic (cobimetinib) to Tecentriq (atezolizumab) could improve survival in the larger pool of CRC patients who are MSI-stable. More than 95% of the 363 patients enrolled in IMblaze370 were MSI-stable, Roche said.
The Swiss drugmaker made careful note that checkpoint inhibitors as monotherapy have not shown clinically meaningful efficacy in these types of CRC tumors — perhaps aiming to head off any questions of Tecentriq's activity.
Sandra Horning, Roche's chief medical officer, said in a statement the results were "not what we hoped for" but noted the company has other studies testing drugs in CRC.
The readout is more of a blow to Roche's much smaller biotech partner Exelixis, which first out-licensed development of Cotellic to Roche in 2006. Under an amended deal, Exelixis receives 50% of profits from the first $200 million of U.S. sales of Cotellic, decreasing thereafter to 30% of sales in excess of $400 million.
To date, Cotellic has not come anywhere near those levels, earning CHF 15 million (about $15 million) globally during the first three months of 2018.
Still, the setback hurts Roche as well. Tecentriq is a distant third to Opdivo and Keytruda in the overall immuno-onoclogy market. Gaining an edge in less competitive tumor types like colorectal cancer would help boost Tecentriq sales even as Roche aims to chip away at rivals' leads in more lucrative indications like lung cancer.
There, Roche has had some reason for optimism. A combination study testing Tecentriq together with Avastin (bevacizumab) and chemotherapy improved survival over Avastin plus combination chemo and could give the Swiss drugmaker a leg up in its commercial efforts.