September 20, 2017
By Alex Keown, BioSpace.com Breaking News Staff
MADRID – Indianapolis-based Eli Lilly is continuing to make the case for cyclin-dependent kinases inhibitors, particularly CDK4 and CDK6, as an effective treatment of cancers.
During a presentation at a Presidential Symposium at the European Society for Medical Oncology 2017 Lilly showed off data from its Phase III Monarch 3 trial that showed its drug abemaciclib was able to cut disease progression or death by 46 percent.
Eli Lilly’s abemaciclib is an oral cell cycle inhibitor of CDK4 and CDK6. By adding abemaciclib to endocrine therapy as part of a treatment regimen, Eli Lilly said the program demonstrated improved progression-free survival in patients with HR+/HER2-negative breast cancer. In patients with measurable disease, the objective response rate was 59 percent in the abemaciclib arm and 44 percent in the placebo arm, according to data.
Levi Garraway, senior vice president of global development and medical affairs at Eli Lilly, told BioSpace that the drug has been developed as a medicine “that could be dosed continuously, in hopes of maximizing its treatment effect, to shrinking tumors and improving outcomes for patients.”
That continuous dosing is something Lilly believes could give the drug an advantage over rival inhibitors in the same space, including Pfizer’s Ibrance and Novartis’ Kisqali. Additionally, the company pointed to the fact that patients with certain challenges, such as liver metastases, showed benefit from the addition of the abemaciclib combination.
As a component of cancer treatment, Garraway said some oncology leaders are suggesting that CDK inhibition is a “new standard of care” in the treatment of advanced HR+ breast cancer. With abemaciclib, Garraway said Eli Lilly continues to believe it has a differentiated molecule that has significant potential for the treatment of women with advanced breast cancer. In the Monarch trials, abemacicilib has been shown efficacy by providing more than seven months in median progression-free survival in endocrine-resistant patients. What’s more, Garraway said, researchers “saw consistent clinical benefit across patient subgroups, including patients with more challenging disease characteristics, with median PFS coming at a later date.”
The drug is showing it’s more effective against CDK4 than CDK6 in enzymatic assays. That will be beneficial when it comes to treating breast cancer, Garraway said.
“CDK4 plays a key role in the development of breast cancer, but CDK6 is important for blood cells. We also hope to be able to target tumor cells wherever they may be in the body, including the brain, a particularly deadly place where cancer cells can spread. Tumors always have dividing cells, so at the end of the day we don’t want to give tumor cells a break from cell-cycle inhibition,” he said.
Although the drug is showing efficacy in treating breast cancer, there are some adverse treatment effects, including diarrhea and neutropaenia. Lilly’s data showed that eight of 10 patients on its treatment experienced diarrhea, although less than 10 percent had grade 3 diarrhea. Lilly has said that most cases of diarrhea are manageable.
Despite the adverse effects, the company is hoping the fact some patients have beat back cancer will be an effective selling point. Garraway said a small number of patients showed a complete response to the treatment. Across the company’s Monarch 3 and Monarch 2 trials, at least 16 patients have shown a complete response, Garraway said.
Lilly is confident enough in the trial data that it submitted a New Drug Application to the U.S. Food and Drug Administration in July. And because the trial data has been so positive, the FDA granted priority review designation to abemaciclib. As a result, Garraway said the company is anticipating approval by the end of the first quarter of 2018.
In addition to breast cancer, Lilly is also studying abemaciclib as a treatment for lung cancer, brain metastases and pancreatic cancer.Lilly’s potential triumph with abemaciclib comes hard on the heels of Lilly’s announcement to terminate up to 3,500 jobs and shutter two R&D sites as it looks to use the savings to invest in new medicines, including abemaciclib. Garraway said the reorganization will result in a “leaner, more nimble global organization” He said the measure will allow the company to accelerate progress toward its long-term goals of growing revenue and “sustaining the flow of life-changing medicines” in the company’s pipeline.
