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

Jazz Pharmaceuticals and Zymeworks have announced positive results from their Phase III HERIZON-GEA-01 study, evaluating the efficacy of their HER2 bispecific antibody, Ziihera, in patients with gastroesophageal adenocarcinoma (GEA). The study's outcomes have been hailed as "practice-changing" by industry analysts, potentially positioning Ziihera as a new standard of care in first-line treatment for HER2-positive GEA.

Study Results and Regulatory Plans

The HERIZON-GEA-01 trial, which enrolled approximately 920 patients with unresectable locally advanced, recurrent, or metastatic HER2-positive GEA, demonstrated significant improvements in progression-free survival for patients treated with Ziihera-based regimens compared to the control group receiving Roche's Herceptin plus chemotherapy.

While specific data points were not disclosed, the companies reported that both Ziihera combinations—one with chemotherapy and another with BeOne Medicines' Tevimbra plus chemotherapy—achieved "highly statistically significant and clinically meaningful improvements" in progression-free survival. Additionally, the Ziihera regimens showed better overall survival rates and met key secondary endpoints, including objective response rate and duration of response.

Based on these positive outcomes, Jazz and Zymeworks plan to file a supplemental biologics license application (sBLA) for Ziihera in the first half of 2026, seeking approval as a first-line treatment option for HER2-positive, locally advanced or metastatic GEA.

Market Implications and Analyst Reactions

The success of Ziihera in the HERIZON-GEA-01 trial has sparked enthusiastic responses from market analysts. Leerink Partners analysts have suggested that Ziihera regimens could potentially replace Herceptin across both PDL1-positive and PDL1-negative GEA patient populations. This expanded potential has led to an increased peak revenue forecast for Ziihera in GEA, now estimated at approximately $2.9 billion.

Jefferies analysts echoed this sentiment, describing the HERIZON-GEA-01 results as "practice-changing" and indicating that Ziihera may become the preferred HER2-targeting backbone in first-line GEA treatment.

Ziihera's Mechanism of Action and Development History

Ziihera is an intravenously administered 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 suppressing uncontrolled cell growth. Additionally, Ziihera stimulates the immune system's anti-cancer activity.

The development of Ziihera has involved multiple collaborations. Originally developed by Zymeworks, the drug became part of a partnership with BeOne Medicines (formerly known as BeiGene) in November 2018. Subsequently, Jazz Pharmaceuticals entered the picture through a licensing agreement with Zymeworks in October 2022.