Eli Lilly has in the past few months unveiled two back-to-back trial flops for Verzenio in prostate cancer. Now, we know exactly how one sputtered.
The addition of Verzenio to Johnson & Johnson’s prostate cancer med Zytiga only pared down the risk of tumor progression or death by 17% in patients with metastatic castration-resistant prostate cancer (mCRPC), according to phase 3 results published in an abstract for the American Society of Clinical Oncology (ASCO) annual meeting. The showing, from the CYCLONE-2 trial, didn’t meet statistical significance.
Patients who received Verzenio and Zytiga lived nearly 22 months without progression, only slightly better than the 20.3 months recorded for those in the Zytiga-alone group. All patients also got the corticosteroid prednisone.
News of the CYCLONE-2 flop came in February. In the same month, Lilly also stopped the CYCLONE-3 trial after an independent data review committee had ruled the study would not succeed. That second study was evaluating Verzenio and Zytiga in metastatic hormone-sensitive prostate cancer.
After these two setbacks, Lilly will not develop Verzenio further in prostate cancer, a Lilly spokesperson confirmed to Fierce Pharma.
CYCLONE-2 was actually a phase 2/3 seamless adaptive trial. After a safety lead-in and smaller-scale testing, an independent data review committee in 2021 recommended that the trial expand into the final stage. The study was designed to target a 45% improvement in progression-free survival, according to the abstract.
Now, the 17% showing was based on investigators’ assessments. A separate evaluation from blinded independent central review was similar with a nonsignificant reduction of 16%.
The Verzenio group saw higher rates of treatment discontinuation and serious adverse events such as anemia, neutropenia and liver enzyme elevation. At least the investigational regimen at this point didn’t show any detriment to patient survival.
With Verzenio out of the picture, Lilly’s prostate cancer plan now rests on PNT2002, a PSMA-targeted radioligand therapy and potential competitor to Novartis’ Pluvicto. Lilly got a stake in the drug through its $1.4 billion acquisition of POINT Biopharma. Lantheus, through a deal signed with POINT in 2022, holds exclusive worldwide rights to the therapy.
A phase 3 trial coded SPLASH recently met its primary endpoint, showing PNT2002 significantly cut the risk of progression or death compared with a change of androgen receptor inhibitor in mCRPC patients who had not received chemotherapy. However, the magnitude of the progression-free survival benefit didn’t look any better than Pluvicto by cross-trial comparison. What’s more, like Pluvicto did in its PSMAfore trial, PNT2002 was linked to a preliminary detriment to patient survival.
Pluvicto’s overall survival result recently turned in its favor after a longer follow-up, and Novartis is busy preparing for an FDA filing toward the middle of the year.
Lilly believes PNT2002 can be competitive in mCRPC with more mature data, the company spokesperson said. Lilly and Lantheus expect to report more mature overall survival results later this year.
Meanwhile, Lilly is gearing up for a possible market showdown between Verzenio and Novartis’ rival CDK4/6 inhibitor Kisqali in post-surgical adjuvant treatment of HR-positive, HER2-negative breast cancer. The indication was the key driver behind Verzenio’s 40% year-over-year sales growth in the first quarter, and Novartis is gunning for a broader label than Verzenio’s.
In addition, researchers will also present at the ASCO meeting results from the phase 3 postMONARCH trial, which tests Verzenio alongside AstraZeneca’s hormone therapy Faslodex in breast cancer patients who have failed on a prior CDK4/6 inhibitor plus endocrine therapy.
Lilly is also studying Verzenio in combination with the company’s oral selective estrogen receptor degrader (SERD) drug, imlunestrant, which is angled at replacing AZ’s Faslodex, an injectable SERD.