After a short delay, Novartis has come up with a positive readout that could significantly expand the market potential of breast cancer drug Kisqali while challenging Eli Lilly.
Kisqali, used on top of endocrine therapy after surgery, significantly reduced the risk of invasive disease recurrence compared with endocrine therapy alone in HR-positive, HER2-negative early breast cancer, Novartis said in a Monday press release.
The results came from the closely watched NATALEE trial. A win there could move Kisqali from metastatic breast cancer into what’s known as the adjuvant setting in early disease. Depending on the exact data, estimates for Kisqali’s peak sales could reach around $4 billion to $5 billion from the current $3 billion, an ODDO BHF analyst wrote in a Monday note.
Novartis’ win is a direct threat to Eli Lilly’s rival drug Verzenio. Back in 2021, Verzenio became the first CDK4/6 inhibitor approved as an adjuvant therapy for HR-positive, HER2-negative early breast cancer. Earlier this month, the FDA expanded that indication by removing a biomarker score requirement for selecting Verzenio patients.
But Verzenio is still only approved in patients at high risk of recurrence with some lymph node involvement. By comparison, Kisqali’s NATALEE trial also included patients at intermediate risk, and Novartis has now reported a “consistent benefit” for its drug in stage 2 and stage 3 early breast cancer regardless of nodal status.
“These data have the potential to be paradigm-shifting for patients at risk of recurrence, including those with no nodal involvement, who have limited well-tolerated options to prevent recurrence,” Novartis’ chief medical officer, Shreeram Aradhye, M.D., said in the press release.
About 80% of patients with HR-positive, HER2-negative breast cancer are diagnosed at an early stage, and the NATALEE trial is targeting an addressable market that’s worth around $6 billion, the ODDO BHF team noted.
The NATALEE readout came slightly later than industry watchers had expected. The trial passed its first interim analysis in late 2022 without a clear signal. The trial has now hit its primary endpoint of invasive disease-free survival at the second interim analysis when at least 425 of altogether over 5,000 patients had experienced disease recurrence.
Now, doctors and analysts will likely scrutinize the NATALEE data to focus on how Kisqali fared in the high-risk population as compared with Verzenio in its own trial and whether the benefit in the intermediate-risk population is large enough to be considered clinically meaningful. Compared with Lilly’s two-year regimen, Novartis is dosing Kisqali for three years but at a lower dose.
In the phase 3 monarchE trial, the addition of Verzenio to endocrine therapy cut the risk of disease recurrence or death by 25.3% in high-risk patients, according to an update presented at the San Antonio Breast Cancer Symposium 2022 meeting last December.
As expected, data on patients’ survival outcomes were immature in both monarchE and NATALEE. The FDA has told Novartis that the agency would consider the disease-free survival data sufficient for a filing as long as Kisqali showed no detriment to overall survival at any analysis point, Novartis CEO Vas Narasimhan told investors during a conference call in October 2022.
The adjuvant indication has boosted Verzenio’s market share among CDK4/6 inhibitors, which also includes Pfizer’s Ibrance. As for Kisqali, despite a solid data package in metastatic breast cancer, the Novartis drug remained a sales underdog. Kisqali's fourth-quarter sales came in at $357 million, whereas Verzenio collected $808 million during the same period.
Nonetheless, thanks to a consistent overall survival showing, Kisqali in January got the CDK4/6 class’s only category 1 NCCN recommendation for first-line treatment of metastatic breast cancer when combined with an aromatase inhibitor.