Jazz and Zymeworks' Ziihera Shows Promising Results in Gastric Cancer Study

Jazz Pharmaceuticals and Zymeworks have announced groundbreaking results from their Phase III HERIZON-GEA-01 study, evaluating the HER2 bispecific antibody Ziihera in patients with gastroesophageal adenocarcinoma (GEA). The study's positive outcomes are set to reshape treatment paradigms in gastric cancer and pave the way for regulatory submissions.

Ziihera Outperforms Standard of Care

The HERIZON-GEA-01 trial, which enrolled approximately 920 patients with HER2-positive, locally advanced, recurrent, or metastatic GEA, demonstrated that Ziihera-based regimens significantly improved progression-free survival compared to the current standard of care. Patients received either Ziihera with chemotherapy or Ziihera combined with BeOne Medicines' Tevimbra plus chemotherapy. The control group was treated with Roche's Herceptin (trastuzumab) and chemotherapy.

Both Ziihera-containing regimens showed "highly statistically significant and clinically meaningful improvements" in progression-free survival. Additionally, the drug met key secondary endpoints, including overall survival, objective response rate, and duration of response.

Mechanism of Action and Development History

Ziihera, administered intravenously, is a bispecific antibody that targets two distinct sites on the HER2 protein. This dual-binding mechanism triggers the internalization of HER2 receptors, effectively reducing their presence on cancer cell surfaces and inhibiting uncontrolled cell growth. The antibody also stimulates the immune system's anti-cancer activity.

Originally developed by Zymeworks, Ziihera's journey to clinical success involved strategic partnerships. In November 2018, Zymeworks entered into an agreement with BeOne Medicines (formerly known as BeiGene). Subsequently, in October 2022, Jazz Pharmaceuticals secured a licensing deal for the promising candidate.

Market Impact and Future Plans

The positive results from the HERIZON-GEA-01 study have significant implications for the gastric cancer treatment landscape. Analysts at Leerink Partners suggest that Ziihera regimens could potentially replace Herceptin across both PD-L1 positive and negative patient populations in GEA. This expanded potential has led to an increased peak revenue forecast for Ziihera in GEA, now estimated at approximately $2.9 billion.

Jefferies analysts described the results as "practice-changing," predicting that Ziihera may become the preferred HER2-targeting backbone in first-line GEA treatment.

With these encouraging data in hand, Jazz Pharmaceuticals and Zymeworks are preparing to file a supplemental biologics license application in the first half of 2026. They aim to secure approval for Ziihera as a first-line treatment option for patients with HER2-positive, locally advanced or metastatic GEA.

While specific data points have not been disclosed, the companies plan to present detailed results from the HERIZON-GEA-01 study at an upcoming medical conference in early 2026. This presentation is eagerly anticipated by the oncology community and is expected to provide further insights into Ziihera's potential to transform gastric cancer treatment.