Eli Lilly's Verzenio fails prostate cancer test as possible Novartis showdown nears

Despite reaching new heights in breast cancer, Eli Lilly’s Verzenio has been sent packing in prostate cancer. 

Verzenio failed to significantly prolong the time before tumor progression or death when added to Johnson & Johnson’s Zytiga and the corticosteroid prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC), Lilly said Tuesday alongside its fourth-quarter financial results.

The phase 3 disappointment, from the CYCLONE-2 trial, comes as Verzenio keeps breaking its own sales records, with its fourth-quarter haul reaching $1.15 billion. It also comes as the Lilly drug is poised to face off against Novartis’ rival CDK4/6 inhibitor, Kisqali, in early-stage breast cancer, the main driver behind Verzenio’s 56% revenue leap in 2023.

Back when Verzenio snagged its first-in-class FDA approval to treat certain patients with HR-positive, HER2-negative early breast cancer after surgery in 2021, the phase 2 portion of CYCLONE-2 had just passed muster with an independent data monitoring committee. With that, the study progressed to phase 3.

But the positive signal was not confirmed in the phase 3 portion in a larger patient population, although the safety profile of Verzenio was consistent with expectations, Lilly’s chief scientific officer, Dan Skovronsky, M.D., Ph.D., said on an investor call Tuesday.

For its part, Novartis’ Kisqali previously showed some promise in mCRPC in an academic-initiated phase 2 trial, but the Swiss company didn’t seem to have enough interest to start late-stage testing.

At Lilly, the prostate cancer program void left by Verzenio’s flop has been filled by PNT2002, a radioligand therapy that Lilly just bought a stake in through its $1.4 billion acquisition of POINT Biopharma. Interestingly, just as Verzenio duels with Novartis’ Kisqali, PNT2002 is a direct rival to Novartis’ radiotherapy Pluvicto.

In the phase 3 SPLASH trial, PNT2002 slashed the risk of progression or death by 29% compared with a change of androgen receptor inhibitor in mCRPC patients who had not received a chemotherapy, according to data released in December by POINT and its partner Lantheus. By comparison, Pluvicto improved radiographic progression-free survival by 57% among chemo-naïve patients in the PSMAfore trial.

At the time of the readouts, both trials had only recorded fewer than 50% of patient deaths for their final overall survival analyses and both showed a negative trend in patient survival for the experimental PSMA radiotherapies. The two trials will need a longer follow-up period before the companies could file with the FDA.

For Verzenio, Lilly’s focus is on preparing for the upcoming showdown in post-surgical breast cancer. Novartis in December submitted an FDA application for Kisqali as an adjuvant therapy. The submission was based on the phase 3 NATALEE trial, in which Kisqali showed a significant benefit in reducing the risk of disease occurrence or death in a broader early-stage breast cancer population than Verzenio did in its own monarchE trial.

The FDA last year expanded Verzenio’s adjuvant indication to remove a biomarker requirement for selecting patients. But to be eligible for the Lilly drug, a patient’s cancer must still have nodal involvement. For its part, Novartis is eyeing node-negative patients as well.

Also handing Novartis a win, Lilly in December reported that the phase 3 Monarch 3 trial for Verzenio as a first-line therapy for advanced breast cancer narrowly missed its overall survival goal. That leaves Kisqali as the only CDK4/6 inhibitor that has a statistically significant overall survival win in the front-line setting.

Verzenio’s current growth is driven by demand in the early breast cancer indication, with “steady performance” in the metastatic indication, Lilly’s CFO Anat Ashkenazi said during Tuesday’s call.

For its part, Kisqali’s $610 million in sales and its 71% year-over-year growth in the fourth quarter came only from the metastatic setting. In that use, Novartis has predicted Kisqali could eventually reach $4 billion in peak sales.