ASCO: Verzenio fails in prostate cancer; Lilly hopes for radiotherapy success

Eli Lilly has faced significant challenges with its drug Verzenio in the realm of prostate cancer treatment. Recently, the company experienced two consecutive trial failures, prompting a shift in strategy. The first setback was revealed when the CYCLONE-2 trial results showed that adding Verzenio to Johnson & Johnson’s Zytiga only reduced the risk of tumor progression or death by a modest 17% in patients with metastatic castration-resistant prostate cancer (mCRPC). This result, which came from phase 3 of the study, did not achieve statistical significance.

Patients in the trial who received the combination of Verzenio and Zytiga had a progression-free survival of almost 22 months, marginally better than the 20.3 months observed in the group that received Zytiga alone. All participants were also administered the corticosteroid prednisone. The news of the CYCLONE-2 trial's failure emerged in February, the same month when Lilly halted the CYCLONE-3 trial after an independent data review committee deemed it unlikely to succeed. The latter trial was investigating Verzenio and Zytiga in metastatic hormone-sensitive prostate cancer.

Following these two setbacks, Lilly has decided to cease further development of Verzenio for prostate cancer. The CYCLONE-2 trial, initially a phase 2/3 seamless adaptive study, had been expanded based on a 2021 recommendation from an independent data review committee, which suggested proceeding to the final stage. The trial aimed for a 45% improvement in progression-free survival, but the actual reduction was only 17%, based on investigators' assessments. A separate blinded independent central review confirmed this with a similarly insignificant 16% reduction.

Patients in the Verzenio group experienced higher rates of treatment discontinuation and serious adverse events, including anemia, neutropenia, and elevated liver enzymes. Despite these issues, the regimen did not negatively impact overall patient survival.

With Verzenio no longer an option, Lilly's focus in prostate cancer now turns to PNT2002, a PSMA-targeted radioligand therapy acquired through its $1.4 billion purchase of POINT Biopharma. This treatment could potentially compete with Novartis’ Pluvicto. The SPLASH phase 3 trial for PNT2002 recently achieved its primary endpoint, demonstrating a significant reduction in the risk of progression or death compared to a change of androgen receptor inhibitor in mCRPC patients who had not yet undergone chemotherapy. However, the progression-free survival benefit was not markedly better than that observed with Pluvicto, and preliminary data indicated a possible negative impact on patient survival.

Pluvicto's overall survival benefits improved with longer follow-up, and Novartis is preparing for an FDA submission. Lilly is optimistic that PNT2002 can remain competitive in mCRPC as more mature data becomes available. Both Lilly and Lantheus, which holds exclusive global rights to the therapy, expect to release more comprehensive overall survival results later this year.

In parallel, Lilly is preparing for a potential competitive market scenario with Verzenio and Novartis’ CDK4/6 inhibitor Kisqali for post-surgical adjuvant treatment of HR-positive, HER2-negative breast cancer. This indication has been a major factor in Verzenio’s 40% year-over-year sales growth in the first quarter. Novartis is also seeking a broader label than Verzenio’s.

Additionally, researchers will present findings from the phase 3 postMONARCH trial at the upcoming ASCO meeting. This study evaluates Verzenio in conjunction with AstraZeneca’s hormone therapy Faslodex in breast cancer patients who have previously failed on a CDK4/6 inhibitor plus endocrine therapy. Lilly is also researching the combination of Verzenio with its oral selective estrogen receptor degrader (SERD) drug, imlunestrant, which aims to replace AstraZeneca's injectable SERD, Faslodex.

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