Long wait for pivotal data on Sanofi's oral SERD ends in failure

Sanofi’s oral selective estrogen receptor degrader (SERD) amcenestrant has flunked a pivotal trial. The failure of amcenestrant as a second-line or later treatment of ER+/HER2- advanced or metastatic breast cancer leaves Sanofi looking to studies in earlier-stage patients to rescue the potential blockbuster.

Paris-based Sanofi was supposed to deliver data from the AMEERA-3 trial in the second quarter of 2021. As the target slipped later into 2021 and ultimately well into 2022, analysts at Jefferies saw “widespread skepticism” about the prospects of amcenestrant moving the needle in second-line or later patients. Even so, Sanofi’s stock opened down 4%, falling below 90 euros ($99) in Paris.

The clinical trial enrolled 367 patients. Participants received either amcenestrant or physician’s choice of a range of drugs, including AstraZeneca’s approved SERD Faslodex. Amcenestrant was no better than the physician's choice at improving progression-free survival (PFS), causing the trial to miss its primary endpoint.

As the Jefferies analysts noted, “optimal therapy after treatment with a CDK 4/6 inhibitor is still unknown, and it is unclear what PFS may be achieved with either fulvestrant or an [aromatase inhibitor] in this setting.” The Sanofi setback adds to evidence it may be hard for oral SERDs to beat the standard of care in the patient population.

“Detailed Phase III EMERALD results for competitor Radius’ oral SERD elacestrant in 2nd/3rd-line breast cancer suggested only a modest 0.9 months benefit on median PFS, albeit a statistically significant 30% risk reduction. Many viewed this as increasing risk for the AMEERA-3 readout in a similar setting, particularly given unlike EMERALD it is not enriched for ESR1-mutation patients, which was the cohort driving the majority of elacestrant’s benefit,” the analysts wrote in a note to investors.

While the failure is a blow to Sanofi, the company, encouraged by the lack of new safety signals, is still forging ahead with two other trials of amcenestrant. The trials are testing amcenestrant in combination with Pfizer’s Ibrance as a first-line treatment and in early-stage breast cancer patients in the adjuvant setting. Sanofi has completed enrollment in the first-line clinical trial.