Nearly two years after the first U.S. approval of Eli Lilly's breast cancer drug Verzenio, the company said Tuesday interim data from a Phase 3 study show proof of a survival benefit among women with metastatic disease.
The result is important, both for Verzenio's prospects as a cancer treatment and as further evidence of the role drugs like it can play in helping women with breast cancer live longer. Detailed data were not disclosed, however, so it's unclear how effective Verzenio was.
The trial, which enrolled 669 pre- and postmenopausal women previously treated, compared Verzenio given together with an older endocrine therapy, fulvestrant, against fulvestrant alone. Previous data from this study had shown the combination lengthened the time until tumors began to grow again, a finding that supported Verzenio's initial approval in Sept. 2017.
Lilly's study, called MONARCH-2, was due to read out overall survival (OS) results in 2020. But a pre-planned interim look showed a statistically significant survival benefit, a finding Lilly was able to call definitive.
"There is a high bar for declaring the pre-planned interim analysis as final, so it does reinforce the strength of the results," said Anne White, head of Lilly Oncology, in an interview with BioPharma Dive.
The pharma plans to disclose full results at an upcoming medical meeting, as well as submit the data to regulators.
Verzenio is one of a class of drugs called cyclin-dependent 4/6 kinase inhibitors, which work by blocking enzymes thought to help drive cancer growth.
Since approval of the first, Pfizer's Ibrance, in 2015, the drugs have been used in combination with existing treatments like fulvestrant or aromatase inhibitors to treat breast cancer that's hormone receptor positive, but negative for a protein called HER2.
Adoption to date, however, is largely based on clinical results that found CDK 4/6 inhibitors extend progression-free survival (PFS), a surrogate measure of efficacy, rather than on survival data.
Lilly's declaration of a survival benefit to Verzenio is only the second time a drug in its class has been found to extend the time women live compared to standard therapy. Earlier this year, Novartis presented data showing its product Kisqali improved overall survival when used as an initial treatment alongside an aromatase inhibitor in younger women.
Phase 3 studies of CDK 4/6 inhibitors in combination with fulvestrant
|Study name||Comparison||PFS on FDA label (hazard ratio)||OS|
|MONARCH 2||Verzenio + fulvestrant vs. fulvestrant||16.4 vs. 9.3 months (0.55)||Positive|
|PALOMA-3||Ibrance + fulvestrant vs. fulvestrant||9.5 vs. 4.6 months (0.46)||Not significant result|
|MONALEESA-3||Kisqali + fulvestrant vs. fulvestrant||20.5 vs. 12.8 months (0.59)||Follow-up ongoing|
Note: Novartis' study also included women not previously treated. SOURCE: Company releases
Lilly hopes the finding from MONARCH-2 will spur greater use of Verzenio, which to date has earned modest sales.
Ibrance, by contrast, has in four years become one of the top-selling cancer drugs on the market. Last year, Pfizer reported $4.1 billion in global revenue from the drug.
Novartis is also anticipating the recent data showing Kisqali's survival benefit will boost adoption in the first-line setting, potentially upping the competitive challenge Lilly faces in the market.
Yet that finding involved pre- and perimenopausal women, in whom metastatic breast cancer tends to be less common and more aggressive.
"This result is in a much broader population," said Lilly's White of the MONARCH-2 study, which involved previously treated postmenopausal women.
Lilly's drug is also approved for first-line use in combination with an aromatase inhibitor, but survival data in that setting are not yet available.
All three CDK 4/6 inhibitors are similarly expensive, costing between $11,000 and $12,000 per month of treatment at list price. Competition between Novartis, Pfizer and Lilly, then, centers on clinical positioning — where survival data is particularly important — as well as the rebates each drugmaker offers insurers.
Lilly has sought to expand its oncology offerings recently, but has hit setbacks. Earlier this year, the company withdrew another drug called Lartruvo (olaratumab) after a confirmatory study found no evidence of a survival benefit.
In January, Lilly bought Loxo Oncology and its portfolio of targeted cancer drugs for $8 billion.