Menarini’s elacestrant, an oral selective estrogen receptor downregulator (SERD), is expected to obtain U.S. FDA approval in February, initiating competition against fulvestrant (brand name: Faslodex), a leading blockbuster drug in the breast cancer treatment market.

On Thursday, the FDA announced that it accepted Menarini’s new drug application for elacestrant and would grant priority review. The FDA is expected to announce an approval decision on Feb. 17, 2023.

The U.S. FDA granted priority review for elacestrant to treat estrogen receptor-positive, HER2-negative metastatic breast cancer.
The U.S. FDA granted priority review for elacestrant to treat estrogen receptor-positive, HER2-negative metastatic breast cancer.

Elacestrant is the first oral SERD that improved progression-free survival in second-line and third-line treatment for estrogen receptor-positive (ER+), HER2-negative metastatic breast cancer, including those with ESR1 mutation.

For the first-line treatment of ER+/HER2- locally advanced or metastatic breast cancer, endocrine therapy (aromatase inhibitor or fulvestrant) in combination with CDK4/6 inhibitor are the standard.

Still, many patients resist the primary therapy, and the disease progresses with various gene mutations.

Literature has shown that mutations in genes like ERBB2, NF1, and ESR1 are associated with resistance to endocrine therapy. ESR1 mutation, in particular, causes resistance to aromatase inhibitors (AI) but does not show resistance to ER inhibitors.

Thus, breast cancer patients whose disease progressed due to ESR1 mutation have the only option to use fulvestrant, which was developed 20 years ago.

This is why there is a high demand for a next-generation SERD that can replace fulvestrant, an intramuscular injection.

Elacestrant has drawn much attention because it was the first oral SERD and proved PFDS improvement compared to the standard treatment in a randomized phase 3 study.

Elacestrant’s safety and efficacy were confirmed in the phase 3 EMERALD trial. The study compared Elacestrant with existing endocrine therapy (AI or fulvestrant) in the second-line and third-line treatment of ER+/HER2- advanced or metastatic breast cancer.

The study enrolled 477 patients, including 228 with ESR1 mutation, indicating that about half of the patients developed resistance to endocrine therapy.

In the study, Elacestrant met the primary endpoint, PFS, in the overall patient group and the ESR1 mutation group, compared to the standard therapy.

PFS at 12 months was 22.32 percent in all patients in the Elacestrant group, vs. 9.42 percent in the standard therapy group. In patients with ESR1 mutation, it was 26.76 percent vs. 8.19 percent, respectively.

Elacestrant’s adverse reactions were reversible and manageable, and the drug demonstrated excellent tolerability, according to the study.

Professor Aditya Bardia of Harvard Medical School, who led the study, announced the results at the San Antonio Breast Cancer Symposium in December (SABCS 2021).

“Elacestrant was well tolerated with manageable and reversible side effects. This therapy has the potential to become the new standard of care for patients with this cancer,” Bardia said.

Menarini applied for marketing approval of elacestrant to the European Medicines Agency in July.

If the treatment wins the nod, it is expected to compete against fulvestrant in the global breast cancer market in the first half of next year.

Copyright © KBR Unauthorized reproduction, redistribution prohibited