Menarini's Orserdu 'first and only' breast cancer therapy of its kind approved by European Commission

The monotherapy more specifically targets estrogen receptor (ER)-positive, HER2-negative, locally advanced or metastatic breast cancer (mBC) with an activating ESR1 mutation who have disease progression following at least one line of endocrine therapy including a CDK 4/6 inhibitor.

Menarini said The European Commission's approval follows the positive opinion of the Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), which was issued in July 2023​. 

With this approval, Orserdu is the first and only therapy specifically indicated for the treatment of ER+, HER2- tumors that harbor ESR1 mutations. 

ESR1 mutations are acquired mutations that develop as a result of exposure to endocrine therapy, and they are found in up to 40% of patients with ER+, HER2- mBC.  ESR1 mutations are a known driver of resistance to standard endocrine therapy, and until now, the tumors that harbor these mutations have been more difficult to treat.

Elcin Barker Ergun, CEO of the Menarini Group said: "We have long known that patients living with metastatic breast cancer need effective and tolerable options which treat their disease while enabling them to focus on the things that matter to them.

“We are proud of delivering a new breast cancer treatment that offers efficacy in a once-daily pill and represents the first innovation in endocrine therapy in nearly two decades; we are also incredibly grateful for the support of the oncology researchers and all the patients who participated in the clinical studies that made today's achievement possible.”

Statistically significant PFS

The approval of Orserdu is supported by data from the phase 3 EMERALD trial, which demonstrated statistically significant progression-free survival (PFS) with elacestrant versus standard-of-care (SOC), defined as investigator's choice of an approved endocrine monotherapy.

The primary endpoints of the study were progression free survival (PFS) in the overall patient population and in patients with ESR1 mutations.  In the group of patients whose tumors had ESR1 mutations, elacestrant achieved a median PFS of 3.8 months vs 1.9 months on the SOC, and reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC.

"With a significant number of ER+ HER2- patients ultimately developing ESR1 mutations at some point in their metastatic journey, it is important to test for ESR1 each time an mBC patient experiences disease progression, to understand what is fueling their breast cancer. Today's approval gives us the first-ever treatment option that directly acts against the very mutations that make this form of breast cancer more difficult to treat, and provides hope to our patients and their families," said Giuseppe Curigliano, professor of medical oncology at the University of Milano and head of the division of early drug development at the European Institute of Oncology, IRCCS, Italy.

The EMERALD phase 3 trial enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator's choice of an approved hormonal agent. The primary endpoints of the study were progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations.  In the group of patients whose tumors had ESR1 mutations, elacestrant achieved a median PFS of 3.8 months vs 1.9 months on the SOC, and reduced the risk of progression or death by 45% vs SOC.