After a failed trial in advanced breast cancer, Sanofi has stopped all studies of amcenestrant, including in early-stage breast cancer.
Sanofi has discontinued the global clinical development program of amcenestrant, an oral selective estrogen receptor degrader (SERD). The decision is based on the outcome of a prespecified interim analysis of the phase 3 AMEERA-5 trial in patients with advanced breast cancer who were ER+/HER2-.
An Independent data monitoring committee (IDMC) found that amcenestrant in combination with Pfizer’s Ibrance (Palbociclib) did not meet the prespecified boundary for continuation in comparison with the control arm and recommended stopping the trial. The trial was assessing emcenestrant as first-line treatment of patients with ER+/HER2- advanced breast cancer. A total of 1,068 patients who had not received any prior systemic anticancer therapies for advanced disease were included.
All other studies of amcenestrant, including in early-stage breast cancer (AMEERA-6), will be discontinued.
“While we are disappointed by this outcome, our research will further the scientific understanding of endocrine therapies in people with breast cancer,” John Reed, M.D., Ph.D., global head of research and development at Sanofi, said in a press release. “Oncology remains a priority area for Sanofi, and we will continue to pursue transformative research to develop new medicines for people living with cancer.”
Company leaders say no new safety signals were observed. Trial participants will be transitioned to letrozole in combination with palbociclib or another appropriate standard of care therapy, as determined by their physician.
AMEERA-5 is the second trial of amcenestrant that failed to meet endpoints. In March 2022, Sanofi announced that the phase 2 AMEERA-3 studying amcenestrant in ER+/HER2- advanced or metastatic breast cancer not meet its primary endpoint of improving progression-free survival (PFS).
Amcenestrant is an optimized oral SERD that binds to the estrogen receptors in breast cancer cells to inhibit their normal function and trigger degradation so they can no longer be used by tumor cells to grow.
The only SERD available in the United States is AstraZeneca’s Faslodex (fulvestrant) and its generics, which are available in an injection formulation. The oncology community was hopeful for an oral SERD, especially for patients with metastatic breast cancer where there is an unmet need.
Other oral SERDS, however, continue in development. The closest to approval is Menarini’s elacestrant. The FDA last week accepted the company’s new drug application (NDA) to treat patients with ER+/HER2 advanced or metastatic breast cancer. The FDA has granted the application priority review and assigned a PDUFA date of Feb. 17, 2023. The NDA was submitted in June 2022.
The NDA submission for elacestrant was supported by results of the phase 3 data from the EMERALD study. The clinical trial data showed that elacestrant reduced the risk of disease progression or death by 30% in all patients and by 45% in patients with ESR1 mutation. Menarini obtained global licensing rights for elacestrant in July 2020 from Radius Health, which conducted the EMERALD study.