STATEMENT: The EC approves ORSERDU® (elacestrant) from Menarini Group for the treatment of patients with breast cancer (2)

- The European Commission approves ORSERDU® (elacestrant) from Menarini Group for the treatment of patients with ER, HER2- locally advanced or metastatic breast cancer with an activating ESR1 mutation

· Every year in Europe, more than 550,000 patients are diagnosed with breast cancer, of which 70% have the disease with positive estrogen receptors (ER)¹; More than 147,000 breast cancer patients in Europe die annually from this disease²

· ORSERDU is the first specific treatment for patients with advanced or metastatic ER, HER2- breast cancer tumors harboring mutations in ESR1, representing the first innovation in endocrine therapy in almost 20 years.

· Mutations in ESR1 are present in up to 40% of ER, HER2-, advanced or metastatic breast cancers, and are a known factor of resistance to standard endocrine therapy, making these tumors more difficult to treat.

FLORENCE, Italy and NEW YORK, Sept. 21, 2023 /PRNewswire/ -- The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics Inc. ("Stemline"), a subsidiary wholly owned by the Menarini Group, announced today that the European Commission has approved ORSERDU® (elacestrant) as monotherapy for the treatment of postmenopausal women and men with estrogen receptor (ER)-positive locally advanced or metastatic breast cancer (MBC). HER2 negative, with an activating ESR1 mutation who have disease progression following at least one line of endocrine therapy that includes a CDK 4/6 inhibitor.

The European Commission's approval follows the positive opinion of the European Medicines Agency (EMA) for Medicinal Products for Human Use (CHMP), 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 harboring mutations in ESR1. ESR1 mutations are acquired mutations that develop as a result of exposure to endocrine therapy and are found in up to 40% of patients with ER, HER2- mBC. ESR1 mutations are a known factor of resistance to standard endocrine therapy and, until now, tumors harboring these mutations have been more difficult to treat.

"We have long known that patients living with metastatic breast cancer need effective, tolerable options that treat their disease while allowing 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 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 researchers at oncology and all the patients who participated in the clinical studies that made today's achievement possible.

"Given that a significant number of HER2- ER patients eventually develop ESR1 mutations at some point in their metastatic journey, it is important to perform ESR1 testing whenever a patient with mBC experiences disease progression, to understand what is fueling their breast cancer. Today's approval "gives us the first treatment option that acts directly against the same mutations that make this form of breast cancer more difficult to treat and provides hope to our patients and their families," commented Giuseppe Curigliano , MD, PhD, professor of Medical Oncology at the University of Milan and head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, Italy.

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 the investigator's choice of an approved endocrine monotherapy. The primary endpoints of the study were 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 versus 1.9 months in SOC, and reduced the risk of progression or death by 45% (PFS HR=0 .55, 95% CI: 0.39, 0.77) versus SOC.

A post hoc subgroup analysis of EMERALD PFS results, 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 before randomization in EMERALD, elacestrant achieved a median PFS of 8.6 months versus 1.9 months in SOC, with a 59% reduction in the risk of progression or death (HR =0.41 95% CI: 0.26-0.63).³

Safety data were consistent with previously reported results. The most common adverse reactions (≥ 10%) with ORSERDU were nausea, increased triglycerides, increased cholesterol, vomiting, fatigue, dyspepsia, diarrhea, decreased calcium, back pain, increased creatinine, arthralgia, decreased sodium, constipation, headache, hot flashes, abdominal pain, anemia, decreased potassium and increased alanine aminotransferase. Important safety information for ORSERDU is provided below.

Stemline and its affiliates will market the product in Europe.

About the EMERALD Phase 3 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 included 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK4/6 inhibitor. Study patients were randomly assigned to receive elacestrant or an approved hormonal agent, chosen by the investigator. The primary endpoints of the study were progression-free survival (PFS) in the overall 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 versus 1.9 months in SOC, and reduced the risk of progression or death by 45% (PFS HR=0 .55, 95% CI: 0.39, 0.77) versus SOC.

About ORSERDU® (elacestrant)

Indication: ORSERDU (elacestrant) monotherapy is indicated for the treatment of postmenopausal women and men with estrogen receptor (ER)-positive, HER2-negative, metastatic or locally advanced breast cancer with an activating mutation of ESR1 who have progression of the disease after at least one line of endocrine therapy that includes a CDK 4/6 inhibitor.

ORSERDU SmPC Important Safety Information

Hepatic Impairment: ORSERDU should be administered with caution at a dose of 258 mg once daily in patients with moderate hepatic impairment (Child-Pugh B). In the absence of clinical data, ORSERDU is not recommended in patients with severe hepatic impairment (Child-Pugh C).

Concomitant use with CYP3A4 inducers and/or inhibitors: Concomitant use of strong or moderate CYP3A4 inhibitors should be avoided with ORSERDU. Concomitant use of strong or moderate CYP3A4 inducers with ORSERDU should be avoided.

Thromboembolic events: Thromboembolic events are commonly seen in patients with advanced breast cancer and have been observed in clinical studies with ORSERDU. This should be taken into account when prescribing ORSERDU to patients at risk.

Adverse reactions:

Serious adverse reactions reported in ≥ 1% of patients included nausea, dyspnea, and thromboembolism (venous).

The most common adverse reactions (≥ 10%) with ORSERDU were nausea, increased triglycerides, increased cholesterol, vomiting, fatigue, dyspepsia, diarrhea, decreased calcium, back pain, increased creatinine, arthralgia, decreased sodium, constipation, headache, hot flashes, abdominal pain, anemia, decreased potassium and increased alanine aminotransferase.

The most common Grade ≥3 (≥2%) adverse reactions of elacestrant were nausea (2.7%), increased AST (2.7%), increased ALT (2.3%), anemia (2%). , back pain (2%) and bone pain (2%).

Nausea: Nausea was reported in 35% of patients. Grade 3-4 nausea episodes were reported in 2.5% of patients. Nausea occurred most frequently in the first cycle and from cycle 2 onward, the incidence of nausea was generally lower in subsequent cycles (i.e., over time).

Elderly: Gastrointestinal disorders were reported more frequently in patients ≥ 75 years of age.

Fertility, pregnancy and breastfeeding:

ORSERDU should not be used during pregnancy or in women of childbearing potential who are not using contraceptive methods. Based on the mechanism of action of elacestrant and findings from reproductive toxicity studies in animals, ORSERDU may cause fetal harm when administered to pregnant women. Women of childbearing potential should be advised to use effective contraception during treatment with ORSERDU and for one week after the last dose.

It is recommended that lactating women do not breastfeed during treatment with ORSERDU and for one week after the last dose of ORSERDU.

Based on findings from animal studies and its mechanism of action, ORSERDU may affect fertility in women and men of reproductive potential.

Effects on the ability to drive and use machines: Fatigue, asthenia and insomnia have been reported in some patients taking ORSERDU. Patients who experience such adverse reactions while driving or using machinery should use caution.

The safety and effectiveness of ORSERDU in children from birth to 18 years of age have not been established.

To report SUSPECTED ADVERSE REACTIONS: EUPV@menarinistemline.com

To file a complaint about a product: EUcustomerservice@menarinistemline.com

To request medical information: EUmedinfo@menarinistemline.com

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

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

About Menarini Group

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

About Stemline Therapeutics Inc.

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

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 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/la-ce-aprueba-orserdu-elacestrant-de-menarini-group-para-el-tratamiento-de-pacientes-con-cancer-de-mama-301934691.html