Akeso’s phase III biliary tract cancer trial meets survival endpoint, but strong control arm narrows relative advantage
Ivonescimab plus chemotherapy extended median overall survival by 2.8 months compared with durvalumab plus chemotherapy. The result was statistically significant but fell short of JPMorgan’s previous optimistic scenario. Phase II lung cancer data for another PD-1/VEGF bispecific antibody support the drug class; the competitive landscape remains to be clarified by phase III data.
Original source：J.P. MorganFirst published on Unhidea：Original source date：
Key takeaway
JPMorgan believes ivonescimab delivered a clinically meaningful survival benefit in first-line biliary tract cancer treatment, but the strong performance of the control arm left relative efficacy below its previous optimistic scenario. A global registrational trial will test the applicability of the Chinese data.
What was positive about the phase III biliary tract cancer results?
The HARMONi-GI1 phase III trial enrolled 682 patients receiving first-line treatment for biliary tract cancer. Median overall survival was 14.9 months with ivonescimab plus chemotherapy and 12.1 months with durvalumab plus chemotherapy, a difference of 2.8 months; the hazard ratio for death was 0.75, and the difference was statistically significant.
Secondary endpoints also supported efficacy: median progression-free survival was 8.4 months and 5.8 months in the two groups, respectively, while objective response rates were 53.8% and 32.5%, respectively.
JPMorgan considers the result clinically meaningful because the comparator was durvalumab plus chemotherapy, already a standard treatment, rather than chemotherapy alone.
Why did the positive result still fall short of the institution’s optimistic expectations?
JPMorgan’s previous optimistic scenario assumed that the phase II signal would carry through to phase III, with the overall survival hazard ratio potentially reaching 0.6 or lower. The actual result was 0.75, representing a smaller benefit than in that scenario.
The bank believes the ivonescimab arm performed broadly in line with expectations, with median overall survival slightly below the 16.8 months recorded in phase II. The more consequential difference came from the control arm: its median overall survival was 12.1 months, above the 9.1 months in the previously referenced TOPAZ-1 China subgroup, potentially narrowing the relative gap between the arms.
In absolute terms, the 2.8-month extension in median overall survival exceeded the 1.3-month extension achieved by the durvalumab regimen in the TOPAZ-1 trial. The latter data supported its approval and adoption as a standard treatment; this is a cross-trial comparison for context.
What will the global trial test?
Summit and ECOG-ACRIN have initiated the global registrational phase II/III EA2251 study, comparing ivonescimab plus chemotherapy with pembrolizumab or durvalumab plus chemotherapy in first-line advanced biliary tract cancer.
JPMorgan sees this as an important step in testing whether the results of the HARMONi-GI1 trial in China can be generalized globally.
What do the lung cancer data for another bispecific antibody in the same class mean?
SSGJ-707/PF’4404 is a PD-1/VEGF bispecific antibody. In its phase II study in first-line non-squamous non-small-cell lung cancer, the confirmed response rate was 75.0% with platinum-based chemotherapy, versus 44.7% with tislelizumab plus chemotherapy; the 12-month progression-free survival rates were 56.0% and 43.0%, respectively.
JPMorgan believes these data support the efficacy potential of the PD-1/VEGF bispecific antibody class. However, the study is still in phase II, has an open-label design and the data are relatively immature, so phase III data are needed to further assess the competitiveness of PF’4404 against ivonescimab.
How does JPMorgan view Akeso’s valuation?
JPMorgan rates Akeso overweight, with a December 2027 price target of 125 Hong Kong dollars. The target is based on discounted cash flow, assuming a weighted average cost of capital of 9.6% and a perpetual growth rate of 3.0%.
The bank forecasts peak ivonescimab sales of more than 7 billion yuan in China and more than 5 billion US dollars outside China. Setbacks in pipeline development or sales of key products falling short of expectations are among the downside risks it lists.
