VERZENIO (abemaciclib) is an oral, continuously dosed, cyclin-dependent kinase 4/6 (CDK4/6) inhibitor indicated for the treatment of metastatic and high-risk early-stage HR+, HER2- breast cancer. At the ASCO 2024 meeting Eli Lilly reported findings from the Phase III study (CYCLONE 2) of VERZENIO (abemaciclib) with ZYTIGA (abiraterone) in patients with mCRPC. CYCLONE 2 was a seamless Phase II/III adaptive trial with a dose-finding safety lead-in. The primary endpoint was investigator-assessed radiographic progression-free survival (rPFS) per RECIST v1.1 and PCWG3. 

Data presented at the conference reported that the addition of abemaciclib to abiraterone did not significantly improve rPFS in patients with mCRPC. The rPFS signal observed at the time of adaptive expansion was not subsequently confirmed in the primary analysis. There was a trend towards numerically more favorable effect sizes in poor prognosis subgroups. The safety of the combination was consistent with the known profiles of the individual medicines. 

KOL insights

“Abemaciclib + abiraterone did not improve rPFS for men with metastatic CRPC in CYCLONE-2. There is a need to investigate molecular determinants of resistance” – Expert Opinion.

“Adding abemaciclib to abiraterone in 1L mCRPC did not significantly improve radiographic progression-free survival. Secondary endpoints and overall survival were also not meaningfully improved. The combination was well-tolerated” – Expert Opinion.

Conclusion

In recent months, Eli Lilly has faced two consecutive trial failures for VERZENIO in prostate cancer. In February, news broke about the CYCLONE-2 trial failure. During its Q4 2023 earnings call, Eli Lilly reported that VERZENIO combined with abiraterone did not meet the primary endpoint of improved radiographic progression-free survival in men with metastatic castration-resistant prostate cancer (mCRPC) in the Phase III CYCLONE-2 study. Furthermore, in its Q1 2024 earnings call, Eli Lilly announced the termination of the Phase III CYCLONE-3 trial evaluating VERZENIO in metastatic hormone-sensitive prostate cancer (mHSPC) due to futility following an interim analysis.

 

As per DelveInsight analysis, the total metastatic castration-resistant prostate cancer market size in the US was estimated to be nearly USD 4.7 billion in 2023, which is expected to show positive growth. Hence, to grab the market opportunity, Eli Lilly is now focusing on PNT2002, a PSMA-targeted radioligand therapy and potential competitor to Novartis’ PLUVICTO. In October 2023, Eli Lilly acquired POINT, with PNT2002 being POINT's lead asset.