Casdatifan’s progression-free survival benefits could help differentiate it from Merck’s Welireg in the kidney cancer arena, according to analysts at Truist Securities.
Arcus Biosciences’ HIF-2a inhibitor casdatifan shows best-in-class potential in metastatic clear cell renal cell carcinoma, demonstrating strong treatment response and encouraging survival rates, according to a Phase I/Ib readout.
The results, presented over the weekend at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, showed that a 100-mg dose once-daily elcited a 33% confirmed overall response rate and a 52% stable disease rate. Disease control rate in these patients was 85%. Arcus did not have progression-free survival (PFS) data at the time of the presentation.
Other dosages of casdatifan—50 mg twice-daily and 50 mg once-daily—also elicited strong response rates, with confirmed overall response rate (ORR) reaching above 25%. Median PFS in patients treated with 50-mg casdatifan twice-a-day had a median PFS of 9.7 months. Arcus has decided to take the 100-mg, once-daily dose forward for further clinical testing, according to the biotech.
As for safety, Arcus noted that casdatifan showed an “acceptable and manageable” adverse event profile across all three doses, with one patient dropping out due to anemia and two others due to hypoxia. At its go-forward dose of 100-mg once-daily, 7% of patients developed serious treatment-emergent adverse events related to the study drug.
In a note to investors Monday evening, analysts at Truist Securities said Arcus’ readout “was strongly positive” and points to casdatifan’s “favorably differentiated” profile from Merck’s Welireg, “an approved competitor in the same drug class” and indicated for advanced renal cell carcinoma.
In particular, Truist pointed to the “strong PFS” data from casdatifan, which was “well above” the firm’s prior projection to support the asset’s differentiation versus Welireg. In the pivotal LITESPARK-005 study, Merck’s HIF-2a blocker achieved median PFS of 5.6 months—though between-study comparisons are inconclusive without a proper and direct head-to-head design.
Still, Truist pointed out notable baseline differences between Arcus and Merck’s respective studies—including the more heavily pre-treated population in the casdatifan study—which the analysts contend “could mean [casdatifan] does better in a more defined Phase III trial.”
Competing with Welireg could prove to be a tough challenge for Arcus, though, as Merck’s drug continues to show strong growth, indicating improving uptake. In 2024, Welireg surged 133% year-on-year to bring in $509 million, a sum that is likely to increase in the coming years, particularly as Merck continues to seek regulatory approvals in overseas markets and works to expand its indications.
Arcus is likewise taking a broad approach to casdatifan to “maximize the opportunity” in the space, the biotech said in its press announcement. Arcus currently has a Phase III study planned for the candidate, which will test it in combination with Exelixis’ Cabometyx for metastatic clear cell renal cell carcinoma. Meanwhile, the biotech is also working with AstraZeneca to run a Phase Ib study of casdatifan with an investigational anti-PD-1/CTLA-4 bispecific antibody for the same indication.
