Italian drugmaker Menarini has succeeded where European Big Pharmas have failed, pushing the first oral selective estrogen receptor degrader (SERD) to treat breast cancer across the FDA finish line.
The agency has signed off on Orserdu (elacestrant) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.
After the therapy previously picked up priority-review and fast-track designations at the FDA, the agency’s final decision came three weeks ahead of deadline. New York City-based Stemline Therapeutics—a subsidiary of Menarini—will commercialize the treatment in the U.S., the companies said.
“The last endocrine therapy approved was about 20 years ago and effective endocrine options for this patient population are needed,” Aditya Bardia, M.D., director of breast cancer research at Mass General Cancer Center and the principal investigator in the EMERALD trial, which supported the approval, said in a release.
Last year, Roche and Sanofi flunked trials in breast cancer for their respective oral SERD candidates giredestrant and amcenestrant. Five months ago, Sanofi discontinued development of its compound.
A candidate from AstraZeneca, camizestrant, excelled in a phase 2 trial last year. The companies have flocked to an opportunity with blockbuster potential, analysts say.
The Menarini drug has a long history. Two months after family-owned Menarini acquired Stemline in 2020 for $677 million, it bought commercial rights for elacestrant from Radius Health for $30 million, plus up to $320 million in milestone payments.
Radius will pass some of those funds onto the original owner of elacestrant, Eisai, which licensed it away in 2006 and is owed royalties. As of 15 months ago, the latest patent for elacestrant was due to expire in 2026.
Orserdu isn’t the first SERD to hit the market for breast cancer. In 2002, AstraZeneca gained a green light in the U.S. for Faslodex and three other subsequent nods to treat various forms of breast cancer. An injected drug, Faslodex reached sales of $1 billion for the first time in 2018, but generic competition arrived the following year and sales were down to $431 million by 2021.
The approval for Orserdu is backed by results from a phase 3 trial of 478 patients that showed it reduced the risk of disease progression or death by 45% versus standard-of-care endocrine therapies in patients whose tumors had ESR1 mutations. The median progression-free survival was 8.6 months on Orserdu, versus 1.9 months for standard of care, in patients who had been treated with a CDK4/6i for at least 12 months, the companies said.
ESR1 mutations are present in up to 40% of ER+, HER2-advanced or mBC cancers and drive resistance to endocrine therapies, Menarini added.
Concurrent with the approval, the FDA also blessed a companion diagnostic, the Guardant360 CDx assay, which helps identify patients who are eligible for Orserdu.