Sanofi is officially out of the race to develop a breast cancer drug in pill form that could compete with a blockbuster injection therapy. The pharmaceutical giant’s challenger, amcenestrant, has failed in a pivotal study, a disappointing result that also spells the end of all clinical trials testing the drug.
The decision, announced Wednesday, follows an interim review of data from the phase 3 clinical trial. Sanofi said the results did not meet pre-defined criteria for continuation and an independent data monitoring committee recommended stopping the trial. Sanofi said no new safety signals were reported in the interim results.
Sanofi was developing amcenestrant as a treatment for patients with advanced breast cancer that is estrogen receptor (ER) positive and human epidermal growth factor 2 (HER2) negative. The small molecule is part of a class of drugs called Selective Estrogen Receptor Degraders (SERDs). These drugs are designed to break down the ER receptor, which is a key driver of cancer cell growth. The only SERD approved by the FDA is AstraZeneca’s Fulvestrant. This drug has validated ER degradation as a way to treat cancer, but it is administered as a painful intramuscular injection and comes with side effects. Major pharmaceutical companies and biotech startups are working to develop oral SERDs that could offer better safety and efficacy.
The phase 3 study of amcenestrant was evaluating the drug as a first-line cancer therapy. The drug was tested in combination with Pfizer’s Ibrance, a standard treatment for ER positive/HER2 negative breast cancer. This pairing compared treatment with letrozole, an older hormone-based cancer treatment, and Ibrance.
The failure of the Sanofi drug in Phase 3 follows a Phase 2 misses who tested the drug itself as a second-line treatment for advanced ER positive/HER2 negative breast cancer. In March, Sanofi reported that this mid-stage trial failed to meet the primary goal of improving progression-free survival, which is a measure of how long patients live without their cancer getting worse. Amcenestrant was also tested in a separate phase 3 study as an adjuvant, a therapy given to prevent the recurrence of treated cancer. The latest failed trial means that adjuvant study will also end, Sanofi said.
Other companies have stumbled with their oral SERD efforts. In April, Roche reported that its drug, giredestrant, failed to meet the primary goal of improving progression-free survival in patients whose advanced ER positive/HER2 negative breast cancer has progressed despite previous treatment. According to the Swiss pharmaceutical giant’s financial report for the first half of 2022, this phase 2 program has been removed from preparation, but phase 3 tests of the drug as a first-line treatment and as an adjuvant therapy continue.
After Sanofi abandoned development of amcenestrant, partners Menarini Group and Radius Health are favorites to commercialize the first oral SERD. The companies reported last fall that their drug, elacestrant, had met the primary goal of its phase 3 trial. They submitted new drug application with the FDA in June. Radius was privately held by two private companiesa deal that closed on Monday.
Sanofi said it will continue to review data from its failed amcenestrant study and will present the results at a future date. Patients who have been treated with amcenestrant will be switched to letrozole in combination with Ibrance or other standard treatment as determined by their doctors.
“Although we are disappointed with this result, our study will contribute to the scientific understanding of endocrine therapies in people with breast cancer,” John Reed, Sanofi’s global head of research and development, said in a prepared statement. “Our sincere gratitude goes out to the patients, families and healthcare professionals involved in the amcenestrant clinical development program. Oncology remains a priority area for Sanofi and we will continue to pursue transformative research to develop new medicines for people living with cancer.”
Public domain image from the National Cancer Institute