Jazz's Ziihera records second survival win in HER2-positive stomach cancer

The phase 3 Herizon-GEA-01 trial showed that Ziihera combined with chemotherapy delivered a statistically significant and clinically meaningful improvement in overall survival compared with trastuzumab — sold as Herceptin by Roche (RHHBY) — plus chemotherapy at the trial's second interim analysis, Jazz announced Monday.

The result builds on an earlier readout in which Ziihera combined with BeOne Medicines' PD-1 inhibitor Tevimbra and chemotherapy produced a 28 per cent survival improvement over the trastuzumab-chemotherapy doublet. At that stage, the Ziihera-chemotherapy combination showed only a favorable trend toward a 20 per cent reduction in death risk, falling short of statistical significance. Jazz said the magnitude of improvement has since increased for both Ziihera regimens, with or without Tevimbra.

"These results reinforce our confidence that Ziihera is the new HER2-targeted backbone therapy in first-line HER2-positive advanced GEA, replacing trastuzumab and extending survival beyond the current standard of care," said Rob Iannone, Jazz's chief research and development officer.

The FDA approved Ziihera for HER2-positive GEA on Aug. 25, though the label carried an unexpected black box warning over diarrhea adverse events, including life-threatening cases. Analysts have largely characterized the safety signal as manageable given the low discontinuation rate observed in the trial. The triplet regimen — Ziihera, Tevimbra and chemotherapy — is approved for tumors with HER2 expression at IHC 3+ and IHC 2+/ISH+, while the doublet is restricted to IHC 3+ patients only.

Jazz's chief commercial officer, Samantha Pearce, has indicated that the triplet is the company's "preferred choice" for all indicated patients except those for whom Tevimbra may be contraindicated, and that commercial efforts will center on that regimen.

Following the approval, Jazz raised its peak sales projection for Ziihera to between $3bn and $5bn, up from a prior target of more than $2bn. Jefferies analysts estimate the drug's peak sales potential in first-line GEA at more than $1.5bn, while Leerink Partners puts the figure at $2.7bn in the indication alone. Jazz estimates that between 3,000 and 4,000 US patients are eligible for first-line treatment in the unresectable disease setting and are tested for HER2.

GEA — encompassing cancers of the stomach, gastroesophageal junction and esophagus — is the fifth most common cancer globally, with approximately 20 per cent of cases classified as HER2-positive.