FDA widens Lilly's Verzenio breast cancer reach, removes test and menopausal status demands

Thanks to two FDA nods, Eli Lilly’s Verzenio doesn’t need results from a biomarker test to treat certain patients with early breast cancer, and it can reach metastatic disease regardless of menopausal status.

The FDA has removed the Ki-67 score requirement for selecting patients with HR-positive, HER2-negative early breast cancer for Verzenio treatment after surgery, Lilly said Friday. Now, eligible patients who’re deemed at high risk of recurrence don’t need a high Ki-67 score but are only defined by commonly used standards around lymph node involvement and tumor size and grade.

Lilly had previously pointed to the Ki-67 restriction as a challenge for Verzenio’s commercial rollout because the test wasn’t typically used to guide treatment choice.

In its original approval of Verzenio in 2021 as an adjuvant therapy, the FDA unexpectedly required an at least 20% Ki-67 score even though the CDK4/6 inhibitor had shown it could cut the risk of invasive cancer recurrence or death in a broader population. At that time, Lilly noted that the FDA applies a high bar to approving drugs in the adjuvant setting, where patients could be cured. The agency wanted longer-term data for high-risk patients with the worst prognostic outlook as determined by a high Ki-67 score.

Lilly recently provided those data. A nearly four-year follow-up of the phase 3 monarchE trial showed that adding Verzenio to endocrine therapy could cut the risk of disease recurrence or death by around 35% in both those patients with Ki-67 below 20% and those above. More importantly, in what might have convinced the FDA to remove the restriction, Verzenio showed a consistent trend in extending patients’ lives in both subgroups.

Expanding patient eligibility criteria is a needed boost for Verzenio. Thanks to the first-in-class adjuvant breast cancer approval, Verzenio’s market share expanded mainly against Pfizer’s Ibrance. But the Lilly med’s total prescription growth rate started to wane in late 2022, according to IQVIA data that SVB Securities tracked.

Meanwhile, all eyes are on Novartis’ phase 3 NATALEE trial for its CDK4/6 rival, Kisqali. The study includes a broader population including both high-risk and intermediate-risk early breast cancer patients. Researchers have already conducted a first interim analysis, Novartis CEO Vas Narasimhan recently said publicly but did not share any result. The final readout is expected by the end of this year when at least 500 patients of the 5,000-plus trial develop recurrence or die.

As Narasimhan noted during the company's fourth-quarter 2022 call, for the adjuvant setting, Novartis is proposing three years of Kisqali treatment after surgery—versus Verzenio’s two years—and is using a lower dose to try to improve the drug’s tolerability profile.

Besides removing a testing limitation in early-stage disease, the FDA also expanded Verzenio’s label in metastatic HR-positive, HER2-negative breast cancer, Lilly said Friday. Verzenio’s use alongside an aromatase inhibitor as initial therapy now includes pre- and peri-menopausal women. The original indication, doled out in early 2018, only covered postmenopausal women.

The FDA recently granted a similar expansion to Pfizer’s Ibrance. At that time, the agency pointed to its guidance on developing drugs for premenopausal women with breast cancer, noting that drugs that target the hormonal axis, like the CDK4/6 inhibitors, are “likely to have generally the same efficacy and safety profile” in pre- and post-menopausal HR-positive breast cancer patients alike.