The Bemarituzumab Setback: Implications for Zai Lab’s Gastric Cancer Strategy and Shareholder Value

The recent attenuation of survival benefits observed in Zai Lab’s Phase III FORTITUDE-101 trial for bemarituzumab has cast a shadow over its gastric cancer strategy, raising critical questions about the biopharma giant’s long-term value proposition. While the interim analysis of the trial demonstrated statistically significant improvements in overall survival (OS) for FGFR2b-positive patients, the final results revealed a diminished effect, prompting Zai Lab to delay regulatory submissions until the FORTITUDE-102 trial—evaluating bemarituzumab in combination with nivolumab and chemotherapy—is completed [1]. This setback underscores the inherent risks of late-stage clinical development and the need for strategic recalibration in biopharma partnerships.

Clinical Setback and Strategic Adjustments

The FORTITUDE-101 trial, which enrolled 547 patients across 37 countries, initially showed a 20% reduction in the risk of death compared to chemotherapy alone at the interim analysis [2]. However, the final analysis revealed a narrower margin of benefit, with Zai Lab attributing the attenuation to factors such as patient heterogeneity and evolving treatment standards [3]. The company has since pivoted to await results from FORTITUDE-102, which is designed to test a triplet regimen of bemarituzumab, nivolumab, and chemotherapy. This trial, expected to report data by mid-2026, could either validate the drug’s potential or further complicate its path to approval [4].

The partnership between Zai Lab and Amgen, which acquired bemarituzumab from Five Prime Therapeutics in 2021, has also faced scrutiny. While Amgen retains global rights to the drug, Zai Lab holds co-development and commercialization rights in China. The weakened results from FORTITUDE-101 have strained this collaboration, with analysts noting that the delayed regulatory timeline could impact Amgen’s ability to secure a first-mover advantage in the FGFR2b-positive gastric cancer market [5].

Financial Implications and Market Position

Despite the clinical setback, Zai Lab’s financials remain resilient. The company reported $110.0 million in Q2 2025 revenues, a 9% year-over-year increase, and reaffirmed its full-year revenue guidance of $560–$590 million [6]. Operating losses have also narrowed, with adjusted losses declining 37% to $34.2 million, positioning Zai Lab to achieve profitability by Q4 2025 [7]. However, the delay in bemarituzumab’s regulatory filing introduces uncertainty. If the FORTITUDE-102 trial fails to replicate the earlier survival benefit, Zai Lab may face significant revenue shortfalls in a market projected to grow at a CAGR of 12.63% to $10.86 billion by 2030 [8].

The gastric cancer therapy landscape is highly competitive, with key players such as Bristol-Myers Squibb (Opdivo) and AstraZeneca (Enhertu) already securing footholds in the FGFR2b and HER2-positive segments [9]. Bemarituzumab’s unique mechanism of action—targeting FGFR2b overexpression in approximately 38% of HER2-negative gastric cancers—positions it as a potential differentiator, but only if its efficacy is confirmed in the triplet regimen [10].

Risk Mitigation and Future Outlook

Zai Lab’s response to the setback highlights the importance of adaptive strategies in biopharma. The company has prioritized cost-cutting measures, reducing R&D and SG&A expenses by 28% year-over-year, while maintaining a robust cash balance of $832.3 million as of June 2025 [11]. Additionally, its pipeline includes promising assets like ZL-1310 (a DLL3-targeting ADC), which demonstrated a 67% objective response rate in small cell lung cancer and is advancing to registrational trials [12]. These efforts aim to diversify revenue streams and mitigate reliance on a single asset.

However, the ocular toxicity profile of bemarituzumab remains a concern. The Phase III trial reported higher frequencies of visual acuity changes, dry eye, and corneal defects compared to earlier studies, raising questions about long-term safety and patient adherence [13]. For Zai Lab to succeed, it must not only demonstrate clinical efficacy in FORTITUDE-102 but also address these safety issues through risk-mitigation strategies such as patient education and dose adjustments.

Conclusion

The bemarituzumab setback serves as a cautionary tale for investors in high-risk, high-reward biopharma ventures. While Zai Lab’s financial discipline and diversified pipeline offer a buffer, the drug’s future hinges on the success of FORTITUDE-102 and its ability to navigate a competitive market. For now, the company’s strategic patience—waiting for definitive data before regulatory filings—reflects a prudent approach. However, the long-term value of its gastric cancer strategy will depend on its capacity to recalibrate partnerships, address safety concerns, and capitalize on the growing demand for targeted therapies.

Source:
[1] Zai Lab Announces Second Quarter 2025 Financial Results [https://zailab.gcs-web.com/news-releases/news-release-details/zai-lab-announces-second-quarter-2025-financial-results-and]
[2] Amgen Announces Positive Topline Phase 3 Results for Bemarituzumab [https://www.amgen.com/newsroom/press-releases/2025/06/amgen-announces-positive-topline-phase-3-results-for-bemarituzumab-in-fibroblast-growth-factor-receptor-2b-fgfr2b-positive-firstline-gastric-cancer]
[3] Update on Amgen's bemarituzumab Phase 3 FORTITUDE-101 Study [https://ir.zailaboratory.com/news-releases/news-release-details/update-amgens-bemarituzumab-phase-3-fortitude-101-study]
[4] FORTITUDE-101 Study Updates 2025: Bemarituzumab ... [https://oncodaily.com/oncolibrary/fortitude-101-bemarituzumab-plus-mfolfox]
[5] Amgen-Zai stomach cancer asset loses benefit in final analysis [https://www.fiercebiotech.com/biotech/amgens-stomach-cancer-candidate-takes-turn-attenuated-os-benefits-final-phase-3-analysis]
[6] Zai Lab Announces Second Quarter 2025 Financial Results [https://zailab.gcs-web.com/news-releases/news-release-details/zai-lab-announces-second-quarter-2025-financial-results-and]
[7] Zai Lab's Path to Profitability: Assessing Financial ... [https://www.ainvest.com/news/zai-lab-path-profitability-assessing-financial-turnaround-pipeline-catalysts-h1-2025-2508/]
[8] Gastric Cancer Therapy Market Size & Share Analysis [https://www.mordorintelligence.com/industry-reports/gastric-cancer-treatment-market]
[9] Gastric Cancer Therapy Market Expansion Forecast Across [https://www.linkedin.com/pulse/gastric-cancer-therapy-market-expansion-forecast-across-uw4qe/]
[10] Amgen's Bemarituzumab-Chemotherapy Combination [https://www.appliedclinicaltrialsonline.com/view/amgen-bemarituzumab-chemotherapy-combination-significantly-improves-overall-survival-unresectable-locally-advanced-metastatic-gej-cancer]
[11] Zai Lab Announces Second Quarter 2025 Financial Results [https://zailab.gcs-web.com/news-releases/news-release-details/zai-lab-announces-second-quarter-2025-financial-results-and]
[12] Zai Lab Announces Second Quarter 2025 Financial Results [https://zailab.gcs-web.com/news-releases/news-release-details/zai-lab-announces-second-quarter-2025-financial-results-and]
[13] Amgen's Bemarituzumab Regimen Improves Survival in FGFR2b+ [https://www.cancernetwork.com/view/bemarituzumab-regimen-improves-survival-in-fgfr2b-gastric-gej-cancer]