European Commission approves ORSERDU® (elacestrant)

21.09.2023 17:14

Menarini Group, an international pharmaceutical and diagnostics company, and Stemline Therapeutics Inc., a wholly owned subsidiary of Menarini Group, announced that the European Commission has approved ORSERDU® (elacestrant) as monotherapy for the treatment of postmenopausal women and men with estrogen receptor (ER) -positive, HER2-negative, locally advanced or metastatic breast cancer (mBC) with an activating ESR1 mutation whose disease continues to progress after at least one endocrine therapy with a CDK 4/6 inhibitor.

The approval by the European Commission follows the positive opinion of the Medical Products for Human Use (CHMP) Committee of the European Medicines Agency (EMA) issued in July 2023. With this approval, ORSERDU is the first and only therapy specifically designed for the treatment of ER+, HER2- tumors ESR1 mutations are provided. ESR1 mutations are acquired mutations that develop as a result of endocrine therapy and occur in up to 40 % patients with ER+, HER2- and mBC. ESR1 mutations are a known cause of resistance to standard endocrine therapies and, until now, the tumors harboring these mutations have been more difficult to treat.

First innovation in endocrine therapy in almost two decades

“We have long known that patients with metastatic breast cancer need effective and tolerable treatment options that allow them to focus on the things that matter to them,” said Elcin Barker Ergun, CEO of Menarini Group. “We are proud to offer a new breast cancer treatment that delivers effectiveness 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 trials that made today’s success possible.”

“Given the significant number of ER+ HER2- patients at some point during the course of their metastatic disease ESR1 mutations develop, it is important to test for ESR1 in every mBC patient whose disease progresses to understand what is fueling their breast cancer. “With today’s approval, we have for the first time a treatment option that directly targets the very mutations that make this form of breast cancer difficult to treat, giving hope to our patients and their families,” said Dr. Giuseppe Curigliano, Professor of Medical Oncology at the University of Milan and Head of the Early Drug Development Unit at the European Institute of Oncology, IRCCS, Italy.

Study shows statistically significant progression-free survival

The approval of ORSERDU is based on data from the Phase 3 EMERALD trial, which demonstrated statistically significant progression-free survival (PFS) with elacestrant compared to standard of care (SOC), which is an approved endocrine monotherapy of the investigator's choice. showed. The primary endpoints of the study were progression-free survival (PFS) rate 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 progression-free survival rate of 3.8 months versus 1.9 months for SOC therapy and reduced the risk of disease progression or death by 45 % ( PFS HR=0.55, 95 % CI: 0.39, 0.77) versus SOC therapy.

A retrospective subgroup analysis of EMERALD PFS results presented at the 2022 San Antonio Breast Cancer Symposium (SABCS) showed that duration of prior CDK4/6i treatment was positively associated with longer progression-free survival with elacestrant, but not with associated with SOC therapy. In patients with ESR1 mutations treated with CDK4/6i for ≥12 months prior to randomization in the EMERALD trial, elacestrant achieved a progression-free survival rate of 8.6 months versus 1.9 months for SOC therapy, with a reduction the risk of progression or death by 59 % (HR=0.41 95 % CI: 0.26-0.63).³

The safety data were consistent with previously reported results. The most common (≥ 10%) adverse reactions to ORSERDU were nausea, increased triglycerides, increased cholesterol, vomiting, fatigue, indigestion, diarrhea, decreased calcium, back pain, increased creatinine, joint pain, decreased sodium, Constipation, headache, hot flashes, abdominal pain, anemia, decreased potassium levels and increased alanine aminotransferase levels.

literature

¹ Decision Resource Group / Clarivate Breast Cancer Landscape / Epidemiology – June 14, 2023
² International Agency for Research on Cancer, World Health Organization – Globocan – 2020
³ Bardia et al. EMERALD Phase 3 study of elacestrant compared to standard endocrine therapy in patients with metastatic ER+/HER2- breast cancer: Updated results by duration of prior CDK4/6i treatment in metastatic breast cancer. SABCS 2022. GS3-01