Lilly’s abemaciclib-Faslodex breast cancer combo trial not stopping early

Eli Lilly ($LLY) will continue its late-stage breast cancer cocktail trial after its CDK4/CDK6 candidate, when used alongside AstraZeneca’s ($AZN) marketed Faslodex (fulvestrant), did not show strong enough data to stop early.  

The Monarch 2 Phase III trial, as part of its protocol, was briefly paused for an independent Data Monitoring Committee (DMC) to assess its survival numbers. The DMC said the study could go on “without modification as the interim efficacy criteria were not met.”

This trial, one of a number studying abemaciclib, saw the drug combined with Astra’s med and pitted against placebo and Faslodex in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer.

The Big Pharma would have hoped that the DMC found some stellar data and stopped the trial early--but is keen to stress that its continuation is still a positive for the company.

“We had stringent criteria set for this interim analysis and we look forward to receiving the final Monarch 2 results in the first half of 2017," said Dr. Richard Gaynor, SVP of product development and medical affairs for Lilly Oncology, in a release. “We remain optimistic that treatment with abemaciclib, in combination with fulvestrant could offer improved outcomes for patients.”

Lilly is some way behind rival Pfizer ($PFE), which has already seen its competing med Ibrance (palbociclib) approved by the FDA, with Novartis ($NVS) wrapping its pivotal study of the CDK4/6 drug LEE011 (ribociclib) early this year with the promising breast cancer data it was looking for.

These drugs are the result of years of research work concentrating on a new way to throw a monkey wrench in an aberrant cell cycle involved in cell replication. Overactive CDK4/6 helps the cancer to accelerate, and checking that activity can rein it back in.

Getting the pioneering approval in the field marks one of the biggest successes Pfizer has had in years, with Lilly and Novartis also keen to get into a market that should yield blockbuster sales for each.

Lilly said that the Monarch 2 trial will continue into the first half of 2017 and will include a final breakdown of progression-free survival, overall survival and safety data.

Tim Anderson, an analyst at Bernstein, said the news may rock some investors, but the overall picture still isn’t clear. “Conventional thinking places place abemaciclib as third-to-market (as much two years behind Ibrance; that much is secured by the news today,” Anderson said.

“Because Ibrance (in the 2L PALOMA-3 trial, analogous to Monarch 2) and LEE011 (in the 1L MONALEESA-2 trial) were stopped early, some reasonably expected Monarch 2 to stop at the interim too. It is a bit unfair--the threshold for significance is intentionally set high at the interim analysis, and differences in design/accrual/events can easily a cause a strong signal to fall short. 

“The early-stage data for abemaciclib don't suggest a difference in activity. But some may wonder if the news foreshadows a real difference in activity--drawing a link between frequent low grade diarrhea to lowered persistence to compromised activity. The problem for investors, is that no one can know which is correct until the data are finally presented a year from now.”

“Lilly will await further data and continue to work with the FDA to inform its submission plan for single-agent abemaciclib, based on the Monarch 1 study,” the Big Pharma added.

This Phase II test looked at abemaciclib on its own in patients with refractory metastatic breast cancer, whose disease had progressed following multiple prior treatments.

Along with Monarch 1 and 2, Lilly currently has three additional trials testing abemaciclib in breast cancer, including a late-stage trial of abemaciclib in combination with a nonsteroidal aromatase inhibitor in patients with HR+, HER2- loco-regionally recurrent or metastatic breast cancer.

- check out the release

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