An FDA approval has officially lifted the curtain on a blockbuster market showdown between Novartis and Eli Lilly in early breast cancer.
The FDA has greenlighted Novartis’ Kisqali, used in combination with an aromatase inhibitor, for the adjuvant treatment of HR-positive, HER2-negative stage 2 and 3 breast cancer that’s at high risk of recurrence following surgery, the company said Tuesday.
The expanded label separates Kisqali from Lilly’s Verzenio by covering patients who don’t have cancer cells in their lymph nodes. Verzenio’s first-in-class nod in HR+/HER2- breast cancer is limited to patients with nodal involvement.
Kisqali’s broad indication almost doubles the size of the patient population eligible for postsurgical adjuvant therapy within the CDK4/6 inhibitor class, Novartis noted.
In November, Novartis estimated that an inclusive node-agnostic label in the adjuvant setting could translate into more than $3 billion in additional annual peak sales for Kisqali, bringing the drug’s total peak projection to $7 billion.
Kisqali is also used to treat metastatic HR+/HER2- breast cancer. Backed by several phase 3 wins showing it can extend patients’ lives, Kisqali saw its sales jump about 48% year over year in the first half of 2024, reaching $1.34 billion.
Similarly, thanks to its until-now unique adjuvant approval, Lilly’s Verzenio grew sales by 42% during the same period to hit $2.38 billion.
The latest approval is based on data from the phase 3 NATALEE trial showing Kisqali’s addition to endocrine therapy lowered the risk of disease recurrence or death by 25.1% compared with endocrine therapy alone in HR+/HER2- stage 2 and 3 early breast cancer.
An exploratory four-year analysis presented Monday at the European Society for Medical Oncology annual meeting showed that after a longer follow-up, Kisqali’s invasive disease-free survival benefit widened to 28.5%. That analysis was not included in the newly approved Kisqali label.
Similar improvements were observed across patient subgroups, including as divided by disease stage and nodal involvement. In patients without nodal involvement, an estimated 92.1% of Kisqali takers remained alive and disease free at four years, versus 87% for the control group. The 5.1% absolute improvement marked an expansion from 2.6% at the three-year mark.
The data are exciting because Kisqali demonstrated the deepening treatment effect even after all patients had come off the Novartis drug at the time of the analysis, Novartis’ chief medical officer, Shreeram Aradhye, M.D., said in a recent interview.
Kisqali's use in early-stage cancer comes at a lower dose than in advanced disease. In the adjuvant setting, the Novartis drug is given for up to three years, which is longer than the Verzenio regimen’s two years. Novartis believes that the longer treatment duration could lead to stronger efficacy over the long term.
In the NATALEE trial, 62.8% of patients completed the full three-year regimen of Kisqali. Among the 37.2% who stopped early, investigators attributed adverse events as the primary reason for 20%.
Treatment discontinuations were mainly driven by asymptomatic laboratory findings such as liver enzyme elevations as mandated by the trial protocol, according to Novartis. In the real world, Novartis has argued that dose adjustments and other measures could help keep patients on treatment.
Aradhye argued Kisqali’s popularity as the most-used CDK4/6 inhibitor in the metastatic setting and its consistent benefit shown across early-stage cancer subgroups could help drive further uptake.