- Menarini Group receives positive CHMP opinion recommending EC approval of ORSERDU® (Elacestrant) for the treatment of patients with ER, HER2- locally advanced or metastatic breast cancer with an activating ESR1 mutation

FLORENCE, Italy and NEW YORK, July 21, 2023 /PRNewswire/ -- Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics Inc. ("Stemline"), a wholly owned subsidiary of Menarini Group, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion on the approval of monotherapy ORSERDU® (elacestrant), indicated for the treatment of postmenopausal women and men with estrogen receptor (ER)-positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation with disease progression after at least one line of endocrine therapy that includes a CDK 4/6 inhibitor.

The CHMP opinion will now be reviewed by the European Commission, which has the authority to grant marketing authorization for medicines for human use throughout the European Union (EU). If approved, Stemline and its affiliates will market the product within Europe. ORSERDU would be the first and only therapy specifically indicated for the treatment of ER, HER2- tumors harboring ESR1 mutations. ESR1 mutations are acquired mutations that develop as a result of exposure to endocrine therapy and are found in up to 40% of ER, HER2-mBC patients. ESR1 mutations are a known driver of resistance to standard endocrine therapy and, until now, tumors harboring these mutations have been more difficult to treat.

"Patients living with metastatic breast cancer need effective and tolerable treatment options. ORSERDU may become the first product, if approved by the European Commission, indicated in ER, HER2- advanced breast cancer with ESR1 mutations, which are a strong driver of treatment resistance in up to 40% of second-line mBC patients. ORSERDU, if approved, will also provide convenient daily oral treatment," said Elcin Barker Ergun, Counselor of the owned by Menarini Group. "We are proud of today's positive CHMP opinion, as it reflects our commitment to developing innovative solutions that address the greatest unmet needs in cancer treatment, and brings us one step closer to providing an important new option to patients and families affected by ESR1, ER and HER2-mutated metastatic breast cancer."

The CHMP's positive opinion for 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 PFS in the general 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 at SOC and reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs. SOC.

A post hoc subgroup analysis of the EMERALD PFS results, which were presented at the San Antonio Breast Cancer Symposium (SABCS) 2022, demonstrated that duration of prior CDK4/6i treatment was positively associated with longer PFS with elacestrant but not with SOC. For patients with ESR1 mutations who were treated with CDK4/6i for ≥12 months prior to randomization in EMERALD, elacestrant achieved a median PFS of 8.6 months vs. 1.9 months in SOC, with a 59% reduction in risk of progression or death (HR=0.41, 95% CI: 0.26-0.63).³

"As an oncologist, it is remarkable that we are on the verge of having the first treatment option for patients with ER, HER2- advanced or metastatic breast cancer harboring ESR1 mutations, which occur in up to 40% of patients in the metastatic setting," said Giuseppe Curigliano, MD, PhD, professor of medical oncology at the University of Milan and chief of the division of early drug development at the European Institute of Oncology, IRCCS, Italy. "Elacestrant has demonstrated efficacy and a manageable safety profile, underscoring the potential benefit this therapy may soon bring to the patients we serve and to the cancer community at large."

The safety data were consistent with previously reported results. Serious adverse reactions reported in ≥ 1% of patients included nausea, dyspnoea, and thromboembolism (venous). The most common adverse reactions (≥ 10%) with ORSERDU were nausea, triglyceride increased, cholesterol increased, vomiting, fatigue, dyspepsia, diarrhea, calcium decreased, back pain, creatinine increased, arthralgia, sodium decreased, constipation, headache, flushing, abdominal pain, anemia, potassium decreased, and alanine aminotransferase increased. The most frequent grade ≥3 (≥2%) adverse reactions for elacestrant were nausea (2.7%), AST increased (2.7%), ALT increased (2.3%), anemia (2%), back pain (2%), and bone pain (2%).

About the Phase 3 EMERALD study (NCT03778931)

The Phase 3 EMERALD trial is a randomized, open-label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in patients with ER , HER2-advanced/metastatic breast cancer. The study 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 investigator's choice of an approved hormonal agent. The primary endpoints of the study were progression-free survival (PFS) in the general patient population and in patients with mutations in the estrogen receptor 1 (ESR1) gene. In the group of patients whose tumors had ESR1 mutations, elacestrant achieved a median PFS of 3.8 months vs. 1.9 months at SOC and reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC.

Elacestrant is also being investigated in several clinical trials in metastatic breast cancer disease, alone or in combination with other therapies: ELEVATE ( NCT05563220); ELECTRA ( NCT05386108); and ELCIN (NCT05596409). Elacestrant is also slated to be tested in early breast cancer disease.

Menarini Group obtained global license rights for elacestrant in July 2020 from Radius Health, Inc. Menarini Group is now fully responsible for global registration, commercialization, and further development activities for elacestrant.

About Menarini Group

The Menarini Group is a leading international pharmaceutical and diagnostics company with revenues of more than $4.4 billion and more than 17,000 employees. Menarini focuses on therapeutic areas with high unmet needs with products for cardiology, oncology, pulmonology, gastroenterology, infectious diseases, diabetes, inflammation and analgesia. With 18 production plants and 9 research and development centers, Menarini products are available in 140 countries around the world. For more information, visit www.menarini.com.

About Stemline Therapeutics Inc.

Stemline Therapeutics, Inc. ("Stemline"), a wholly owned subsidiary of the Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel cancer therapies. Stemline markets ORSERDU® (elacestrant) in the United States, an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy. Stemline is also marketing ELZONRIS® (tagraxofusp-erzs), a new CD123-targeted treatment for patients with blastic plasmacytoid dendritic cell neoplasia (BPDCN), an aggressive blood cancer, in the US and Europe, which is the only US and EU-approved treatment for BPDCN to date. Stemline also markets NEXPOVIO® in Europe, an XPO1 inhibitor for multiple myeloma. Stemline also has an extensive clinical portfolio of small molecules and biologics in various stages of development for a wide range of solid and hematologic cancers.

¹ Decision Resource Group / Clarivate Breast Cancer Landscape / Epidemiology –14 de junio de 2023

² International Agency for Research on Cancer, World Health Organization – Globocan – 2020

³ Bardia et al. EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER /HER2- metastatic breast cancer: Updated results by duration of prior CDK4/6i in metastatic setting. SABCS 2022. GS3-01

Logo - https://mma.prnewswire.com/media/1958938...

View original content: https://www.prnewswire.com/news-releases/menarini-group-recibe-la-opinion-positiva-del-chmp-para-orserdu-elacestrant-301883210.html