Zejula Confirms Second Survival Benefit in First-Line Gastric Cancer Treatment

Jazz Pharmaceuticals’ bispecific antibody cancer drug Zejula has confirmed a second survival benefit in first-line gastric cancer treatment.

According to U.S. pharmaceutical news outlet Fierce Pharma on the 31st local time, Jazz Pharmaceuticals announced that the combination regimen of Zejula significantly improved overall survival (OS) in the second interim analysis of the Phase 3 HERIZON-GEA-01 clinical trial.

In this analysis, the group receiving Zejula plus chemotherapy showed a statistically significant and clinically meaningful improvement in survival compared with the group receiving trastuzumab (brand name Herceptin) plus chemotherapy.

In the first interim analysis, the triplet regimen of Zejula, BeiGene’s PD-1 inhibitor Tevimbra and chemotherapy reduced the risk of death by 28% compared with the trastuzumab combination group. At that time, the Zejula-plus-chemotherapy doublet showed a trend toward a 20% reduction in the risk of death but did not meet the threshold for statistical significance.

Jazz Pharmaceuticals said that in the second analysis, both Zejula regimens showed greater improvements, regardless of whether Tevimbra was included.

Rob Iannone, head of research and development (R&D) at Jazz Pharmaceuticals, said, "These results reinforce our confidence that Zejula is a new HER2-targeted regimen that can replace trastuzumab in the first-line treatment of HER2-positive advanced gastroesophageal junction adenocarcinoma (GEA)."

The U.S. Food and Drug Administration (FDA) expanded Zejula’s indication to HER2-positive GEA on the 25th of last month. Immediately after the approval, Jazz Pharmaceuticals raised its peak-sales forecast for Zejula from more than $2 billion to $3 billion-$5 billion.

The approval included a boxed warning for diarrhea as an adverse reaction. However, analysts assessed the safety issue as manageable, citing the relatively low treatment-discontinuation rate in clinical trials.

Under the FDA label, the Zejula-Tevimbra-chemotherapy triplet regimen is indicated for tumors with HER2 expression of IHC 3+ and IHC 2+/ISH+. The Zejula-plus-chemotherapy doublet is limited to patients with IHC 3+ tumors.

Samantha Pierce, chief commercial officer (CCO) at Jazz Pharmaceuticals, said during an analyst call on the 25th of last month that, except for patients for whom Tevimbra is contraindicated, the company considers the triplet regimen the "preferred choice."

Jefferies analysts estimated Zejula’s peak sales potential in first-line GEA treatment at more than $1.5 billion based on the FDA label. Leerink Partners analysts projected that sales could reach $2.7 billion.

GEA includes gastric cancer, gastroesophageal junction cancer and esophageal cancer and is the fifth most common cancer worldwide. According to Jazz Pharmaceuticals, approximately 20% of patients are HER2-positive, representing about 8,000 patients annually in the United States.