The implementation of new strategies in the hepatocellular carcinoma (HCC) market will lead to increased opportunities for manufacturers. Additionally, regulatory incentives, such as orphan drug designations and fast track approvals, have led to a dynamic market.
Following the approval of Roche’s Avastin (bevacizumab) plus Tecentriq (atezolizumab) for first-line treatment of HCC in May 2020, the focus of HCC R&D has shifted toward combination therapies of programmed cell death protein 1 (PD-1) / programmed death-ligand 1 (PD-L1) inhibitors plus multikinase inhibitors, vascular endothelial growth factor (VEGF) inhibitors, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. These combination therapies are well represented in late-stage development for HCC. Furthermore, the majority of late-stage HCC pipeline drugs are already marketed for other oncology indications, and HCC serves as an opportunity to expand the existing market for these products. These previously marketed drugs include AstraZeneca’s Imfinzi (durvalumab) (first approved for advanced bladder cancer in 2017), Merck’s Keytruda (pembrolizumab) (first approved for advanced melanoma in 2014), Roche’s Avastin (first approved for metastatic colorectal cancer in 2004), Roche’s Tecentriq (first approved for urothelial carcinoma in 2016), Bristol-Myers Squibb’s (BMS’) Opdivo (nivolumab) (first approved for advanced melanoma in 2014), BMS’ Yervoy (first approved for melanoma in 2011), Eli Lilly’s Cyramza (first approved for stomach cancer in 2014), Bayer’s Nexavar (first approved for advanced renal cell carcinoma in 2005), Eisai’s Lenvima (first approved for thyroid cancer in 2015), Bayer’s Stivarga (first approved for advanced colorectal cancer in 2012), and Exelixis’ Cabometyx (first approved for advanced renal cell carcinoma in 2016). Another effective strategy for gaining market share is label expansion within HCC to the early and intermediate stages.
Despite the company’s strong presence in oncology, Novartis did not have a stake in the HCC market until this month when it announced a collaboration with BeiGene that strategically expands its oncology pipeline by in-licensing tislelizumab, a Phase III PD-1 inhibitor, from BeiGene. The collaboration is mutually beneficial for both parties since BeiGene, a Chinese biopharmaceutical company, gained the recognition of an international pharmaceutical company to support the potential commercialisation of tislelizumab, and Novartis obtained access to a promising Phase III pipeline drug that will ease entry and improve uptake in the HCC market. In August 2020, this strategy was used by Eli Lilly, a world-class biopharmaceutical company, when the company expanded its pipeline into HCC by receiving the rights to develop, manufacture, and commercialise Tyvyt (sintilimab) outside of China from Innovent Biologics, a China-based biopharmaceutical company. The innovator, Innovent Biologics, retained rights to Tyvyt within China.
Manufacturer enthusiasm has resulted in the saturation of pipeline products in the same class of drugs throughout the HCC pipeline. Although key opinion leaders (KOLs) interviewed by GlobalData are happy with the progress being made in this field, considering the variety of mechanisms of action and the wave of new entrants, they also highlighted the emergence of “me-too” drugs and combinations. For example, tislelizumab is a pipeline drug for first-line advanced HCC and will be in competition with other anti-PD-1 / PD-L1 monotherapies such as BMS’s Opdivo and AstraZeneca’s Imfinzi. However, KOLs were less excited about monotherapies in this space. Fortunately, Novartis and BeiGene announced that under their strategic collaboration agreement, both companies can conduct clinical trials globally to investigate combinations of tislelizumab with other cancer treatments. Therefore, this could be a promising start for Novartis as a novice in the HCC market.
The implementation of new strategies in the HCC market will lead to a flood of new entrants, providing more options to physicians and a better quality of life for HCC patients. However, the crowded pipeline makes it difficult for new competitors to gain share in the HCC market unless an innovative strategy or novel combination is being offered.