Sanofi is stopping development of its oral selective estrogen receptor degrader (SERD) amcenestrant. A failed phase 3 interim analysis dealt the death blow to the program, which Sanofi once saw as the future “endocrine backbone therapy” in breast cancer.
Hopes for amcenestrant took a hit in March, when Sanofi revealed the failure of an oft-delayed phase 2 trial that studied the drug as a monotherapy in ER-positive, HER2-negative breast cancer. While stung by the failure, Sanofi pushed ahead with two other clinical trials of the candidate, including the AMEERA-5 study that failed Wednesday.
In AMEERA-5, Sanofi tested the effect of adding amcenestrant or letrozole to Pfizer’s Ibrance as a first-line treatment in 1,068 patients with ER-positive, HER2-negative advanced breast cancer. Amcenestrant fell short of the pre-specified bar for continuation at the interim analysis, leading to a recommendation to stop the clinical trial.
Sanofi complied with the recommendation and went a step further, stopping the AMEERA-6 clinical trial in early-stage breast cancer and all other work on amcenestrant. Participants in the amcenestrant arm of AMEERA-5 will switch to letrozole, in combination with Ibrance, or whatever standard of care their doctor thinks is appropriate.
Trials of other oral SERDs suggest there may have been a path forward for amcenestrant that Sanofi has opted not to take. While the French Big Pharma ran all-comer clinical trials, Menarini and Radius Health enriched their EMERALD phase 3 study with patients with the ESR1 mutation. EMERALD had co-primary endpoints covering carriers of the ESR1 mutation and the broader patient population.
If, as EMERALD suggests, oral SERDs are most effective in people with ESR1 mutations, subsequent studies of amcenestrant in the subpopulation may have been more successful. However, Menarini and Radius are out in front, having filed for FDA approval in June, and the lack of efficacy in the all-comer trial would limit the market open to amcenestrant.
While Sanofi is bowing out, AstraZeneca, Eli Lilly and Roche remain in the oral SERD race. Roche suffered its own setback in April, when giredestrant failed a midphase clinical trial, but is continuing to enroll patients in its pivotal program. Roche lists progression-free survival in people with ESR1 mutations as a secondary endpoint in one of its phase 3 trials, as does Lilly.
Sanofi’s shares were trading down 6% at $42.08 premarket Wednesday.