- Eli Lilly's closely watched breast cancer treatment met the primary endpoint of a Phase 3 study, according to topline results from an interim analysis released Monday.
- Abemaciclib inhibits two cycline-dependent kinsases (CDK), proteins that regulate cellular proliferation. In the late-stage MONARCH 3 trial, breast cancer patients taking a combination of Lilly's drug and an aromatase inhibitor had significantly improved progression-free survival versus those on placebo and an aromatase inhibitor.
- "Today marks another important milestone in our clinical development program for abemaciclib, a drug we believe has the potential to be best in class," Levi Garraway, Lilly Oncology's SVP for global development and medical affairs, said in an April 24 statement.
Garraway's word choice is significant, according to a note from Evercore ISI analyst Umer Raffat, because Lilly hasn't described the drug as "best in class" in the past. If approved, abemaciclib would face stiff competition in the CDK 4/6 inhibitor space from Pfizer's Ibrance (palbociclib) and Novartis' recently-approved Kisqali (ribociclib), so this increased optimism that Lilly is sitting on some strong interim data.
MONARCH 3 evaluated 493 postmenopausal women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who had not previously received treatment for the advanced disease. Patients in the treatment arm received abemaciclib and either letrozole or anastrozole.
Hitting the primary endpoint early puts abemaciclib on relatively equal ground with Ibrance, which was able to stop Pfizer's PALOMA-2 trial after interim analysis. And having data for abemaciclib in combination with either of two aromatase inhibitors may give Lilly a slight leg up on the competition. Ibrance, for example, is approved for use only in combination with letrozole.
Where Lilly's drug loses an edge, however, is on safety — particularly diarrhea. In the mid-stage MONARCH 1 study, 19.7% of patients demonstrated grade 3 diarrhea and close to 90% had at least grade 1. Conversely, the PALOMA-2 study showed 20% of patients had grade 1 diarrhea and none had grade three or higher.
"The key challenge has been diarrhea rates," Raffat said in his note. "But on the flip side, abemaciclib can be dosed continuously whereas Ibrance is dosed for 3 [weeks] and 1 [week] off," due to tolerability reasons.
Raffat added that Lilly has lowered the testing dose of its drug from 200 mg twice daily in MONARCH 1 to 150 mg twice daily in MONARCH 3. The company may also have used more imodium to curb instances of diarrhea, he said, which will be something to look for when more extensive data comes out.
While most of the efficacy and safety results from the interim analysis won't be available until an unspecified medical meeting in the latter half of 2017, Lilly did reveal its drug met a secondary endpoint for objective response rate. Other secondary objectives included overall survival, duration of response and clinical benefit rate.
Lilly plans to start submitting MONARCH 1 and MONARCH 2 data for abemaciclib's approval in the second quarter and MONARCH 3 data in the third quarter.
In spite of rival therapies, the CDK 4/6 inhibitor market is still relatively uncrowded and could offer Lilly big returns. Ibrance raked in $2.14 billion last year, according to Pfizer's most recent annual report, and consensus estimates have Lilly's drug yielding around $2 billion in peak annual sales.