Bayer’s Stivarga (regorafenib) has been widely accepted as a monotherapy treatment option for patients with refractory metastatic colorectal cancer (CRC). 

It has limited clinical efficacy, and many clinicians have stated that the overall survival achieved with the drug is no more than six months, which many physicians deem insufficient. Stivarga’s prescribing potential has been hampered because it is poorly tolerated by patients and can dramatically reduce the quality of life for patients with advanced disease.

To improve upon and further demonstrate the potential of Stivarga, Bayer has been actively trialling the drug in many treatment lines. Little success has been seen with the monotherapy regimen in the early and adjuvant settings for CRC. However, 2019 has seen an emergence of positive early-stage clinical data showing the potential Stivarga may have when used in combination with other drugs for the treatment of microsatellite stable colorectal cancer (MSS CRC), which accounts for 85% of CRC cases. 

On May 26, 2019, top-line data from the 1b REGONIVO/EPOC1603 trial established the maximum tolerated dose and recommended dose for Stivarga (80mg) when used in combination with Bristol-Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab). The trial also showed encouraging anti-tumour activity in MSS CRC, with a 33% response rate in the trial patient population. Although this is very early-stage clinical trial data, GlobalData considers it to be promising as checkpoint inhibitors could not be used in the MSS CRC population until now.  

On September 9, Cytodyn announced clearance by the US Food and Drug Administration (FDA) to proceed with a Phase 2 single-arm study designed to test the hypothesis that the combination of leronlimab, administered as a subcutaneous injection, and Stivarga, administered orally, would increase progression-free survival in patients with CCR5-positive MSS CRC. 

Leronlimab is an investigational humanised immunoglobulin G4 (IgG4) monoclonal antibody (mAb) that blocks CCR5, a cellular receptor that is important in the tumour invasion and metastasis, and which was already granted FDA Fast Track designation in May 2019 for metastatic triple-negative breast cancer.  

In the future, it will become increasingly difficult for drug companies to enter early lines of therapy in CRC, as it is dominated by capecitabine or other chemotherapy and Roche’s Avastin (bevacizumab). Therefore, drug companies need to look for novel ways to extend the life cycle of their branded treatments. If either of these trials is successful, it will allow Bayer to gain access to patients in earlier treatment lines, and therefore increased profitability from Stivarga. The drug’s patent is due to expire in 2031 in the US and 2028 in Europe, so there is sufficient time for Bayer to establish a stronger position for Stivarga in the CRC treatment paradigm.  

Forthcoming report

GlobalData (2019) Colorectal Cancer – Global Drug Forecast and Market Analysis to 2028, to be published.