Survival questions delay bemarituzumab

When Amgen and Zai Lab announced positive phase 3 results with their anti-FGFR2b monoclonal antibody bemarituzumab in June, safety concerns were already high. On Wednesday a quiet disclosure by Amgen that the data had unexpectedly worsened means that those worries have only deepened. 

In June the companies reported that bemarituzumab plus chemotherapy provided a clinically meaningful and statistically significant improvement in overall survival at a prespecified interim analysis of the Fortitude-101 trial. However, at the Wells Fargo healthcare conference, Amgen revealed that Fortitude-101 showed a decreased overall survival benefit at final analysis. 

Surprisingly, the disclosure didn't come as a result of questioning, but was made in prepared remarks by Amgen's chief medical officer, Paul Burton. Zai, for which any delay to bemarituzumab would be a material event, issued a statement on Wednesday, and its shares closed down 6%, and fell another 7% on Thursday morning.

Ocular events

Toxicity issues have long overshadowed this programme. Back in June, Amgen noted that Fortitude-101’s ocular events were “consistent” with those seen in the phase 2 Fight study, where 67% of the patients experienced them, but acknowledged the toxicities appeared with “greater frequency and severity” in the phase 3 bemarituzumab arm.

The latest update suggests these toxicities may have been more severe than initially suggested. Full data will be presented at a future major medical meeting, which should clarify the full extent of these adverse events. 

Until then it remains unclear how significant the detriment in Fortitude-101's OS benefit has been. All investors have to go on are Burton's disclosures at the Wells Fargo conference, namely that "at a recently completed final analysis the magnitude of the survival benefit has decreased".

An additional problem is that bemarituzumab's filing appears to have been delayed. As a result of the OS problem both companies now say they will await results from the ongoing Fortitude-102 trial, testing an Opdivo/chemo triplet, which are expected by the end of 2025 or the first half of 2026, before deciding on a regulatory pathway. 

While for Amgen bemarituzumab is less important than for Zai, it is nevertheless a high-profile R&D project. Amgen paid $1.9bn to acquire its originator, Five Prime Therapeutics, in 2021, some years after that biotech tied up with Zai over the asset.

Phase 3 trials of bemarituzumab

Note: GEJ=gastro-oesophageal junction. Source: OncologyPipeline.