Anti-GBM (GOOD-IDES-02) pivotal phase 3 failed, Hansa announced this morning. Quite a big and surprising disappointment for me. This emphasizes that one cannot draw very big conclusions from comparisons to historical cohorts yet in phase 2, no matter how good it looks.
The phase 3 primary endpoint (eGFR 6 months) did not differ in the imlifidase+SoC arm from control-SoC. Although imlifidase rapidly removed anti-GBM antibodies and approximately 60% of patients were dialysis-free at 6 months, the control group achieved almost the same level, resulting in no statistical difference. In phase 2, there was talk of a historical control group that achieved only about 20-25% dialysis-free status.
A key reason why phase 3 “lost” to phase 2 is the study design: phase 2 was open-label, uncontrolled, and compared results to that (perhaps too loosely) selected historical cohort, whereas in phase 3, the standard of care was defined in the protocol as exceptionally aggressive (immediate and intensive PLEX + cyclophosphamide + steroids). This significantly raised the results of the control group and eroded the incremental benefit of imlifidase, even though the biological effect itself worked as expected. In other words, imlifidase did work, but when the disease was diagnosed quickly and aggressive SoC was started immediately in this experimental setup, there was no additional benefit from imlifidase.
In practice, the regulatory pathway for the anti-GBM indication is non-existent after this, and the value of this indication can be set to zero in Excel.