Eli Lilly's growth drivers, Verzenio and Jardiance, suffer clinical setbacks

Besides the diabetes and obesity duo of Mounjaro and Zepbound, the SGLT2 inhibitor Jardiance and the CDK4/6 cancer drug Verzenio were cited as the main growth drivers for Eli Lilly’s first quarter. But both meds had some bad news to report from late-stage clinical trials.

First up, Lilly has decided to terminate the phase 3 CYCLONE-3 trial testing Verzenio alongside Johnson & Johnson’s antiandrogen therapy Zytiga and the corticosteroid prednisone in metastatic hormone-sensitive prostate cancer (mHSPC), the company said Tuesday in its first-quarter earnings release.

The decision comes as an interim analysis found the Verzenio combo was unlikely to beat Zytiga-prednisone alone at delaying disease progression or death.

As for Jardiance, the EMPACT-MI trial showed the Boehringer Ingelheim-partnered med did not lead to a significantly lower risk of a first heart failure-related hospitalization or all-cause death compared with placebo in patients who had had an acute myocardial infarction. Jardiance’s risk reduction was 10%, which again was not statistically significant, according to Lilly.

The two readouts, while disappointing, likely won’t affect Verzenio’s and Jardiance’s current commercial performance, even though both drugs face fierce in-class competition.

For Verzenio, no CDK4/6 inhibitor is approved in mHSPC anyway. However, the phase 3 CYCLONE-3 flop adds to a separate Verzenio failure in the phase 3 CYCLONE-2 study earlier this year in metastatic castration-resistant prostate cancer (mCRPC).

Because of the prostate cancer defeat, Lilly took an impairment charge of about $75 million in the first quarter.

The two back-to-back setbacks brought into question Lilly’s decision to advance Verzenio in the first place. Previously, the phase 2 CYCLONE-1 trial missed its primary endpoint of overall response rate, although investigators found modest single-agent clinical activity for Verzenio in heavily pretreated mCRPC. By comparison, Novartis didn’t seem to have made any late-stage development plans for its rival CDK4/6 inhibitor Kisqali in prostate cancer.

Lilly is bracing for a potential impact from Novartis’ Kisqali in the all-important postsurgical adjuvant treatment of early-stage, HR-positive, HER2-negative breast cancer. With an FDA filing in December, Novartis is gunning for approval in a larger patient population than Verzenio’s current indication.

Thanks to its first-in-class FDA nod as an adjuvant therapy in 2021 and an expansion of that label in March 2023, Verzenio grew its U.S. total scripts by 32% year over year in the first quarter. While Verzenio’s $1.05 billion sales in the first three months marked a 40% year-over-year growth, the number came 3% below analysts’ expectations.

Turning to Jardiance. The 10% risk reduction from EMPACT-MI was published earlier this month in the New England Journal of Medicine. The data was gleaned after a median follow-up of 17.9 months. At that time, a first hospitalization for heart failure or death from any cause occurred in 267 patients (8.7%) in the Jardiance arm, compared with 298 patients (9.1%) in the placebo group. With this short follow-up, Jardiance’s effectiveness was understandably more pronounced on the hospitalization component, with a 23% risk reduction, whereas the death risk reduction was low at 4%.

Although the trend was positive, Jardiance’s readout here in heart attack patients represents a departure from the significant cardiovascular outcomes benefits it has shown before in heart failure, Type 2 diabetes with high cardiovascular risk, and chronic kidney disease.

Still, Jardiance need not worry. In the DAPA-MI trial in patients with acute myocardial infarction, AstraZeneca’s rival SGLT2 inhibitor Farxiga showed “no impact” on a composite endpoint of cardiovascular death or hospitalization for heart failure compared with placebo. After about a year of treatment, the event rate on that composite endpoint was 2.5% for Farxiga, versus 2.6% for placebo, according to results published in NJEM Evidence in November.

Jardiance, which is on its way to a Medicare price cut under the Inflation Reduction Act, is still churning out major sales growths these days. As the SGLT2 market share leader in the U.S., Jardiance saw its U.S. total scripts grow 24% year-over-year in the first quarter. Lilly’s reported revenue for the drug was $687 million, which despite a 19% year-on-year increase, missed Wall Street’s consensus by 5%.

In contrast, thanks to the launch of an authorized generic, Farxiga’s global revenue turned up a 45% growth in the first quarter, reaching $1.89 billion. The number handily beat the consensus projection by 19%.