Stemline News

• ESR1 mutations are present in up to 40% of ER+, HER2- advanced or metastatic breast cancers.
• ESR1 mutations are a known driver of resistance to standard endocrine therapy, and so far, have been difficult to treat.
• ORSERDU is the first endocrine innovation in more than 20 years, specifically addressing ESR1 mutations, a major unmet need.

FLORENCE (Italy) and New York City (U.S.) January 30th, 2023 – The Menarini Group (“Menarini”), a leading Italian pharmaceutical and diagnostics company, announced today that the U.S. Food and Drug Administration (FDA) has approved ORSERDU for the treatment of postmenopausal women or adult men, with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline Therapeutics (“Stemline”), a wholly-owned subsidiary of the Menarini Group, headquartered in New York and focused on bringing transformational oncology treatments for cancer patients, will commercialize ORSERDU in the U.S.

“The FDA approval of ORSERDU marks the first ever therapy for ER+, HER2- advanced or metastatic breast cancer patients with ESR1 mutations and we are very proud to offer a targeted therapy addressing this huge unmet need,” commented Elcin Barker Ergun, Chief Executive Officer of the Menarini Group. “We are grateful to the patients, investigators and administrators who participated in the clinical trials that led to this remarkable innovation.”

ORSERDU is approved under the FDA’s Priority Review and Fast Track designation based on the results of the registrational Phase III trial EMERALD, that demonstrated statistically significant progression-free survival (PFS) with elacestrant vs SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane), meeting both primary endpoints in all patients and in those patients whose tumors harbor ESR1 mutations.

In the group of patients whose tumors had ESR1 mutations, elacestrant reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC. A post-hoc analysis of the PFS results based on the duration of prior CDK4/6i inhibitors (CDK4/6i) usage was presented at San Antonio Breast Cancer Symposium (SABCS) in December 2022. The median PFS was 8.6 months on elacestrant vs 1.9 months for SOC, in those patients whose tumors harbored ESR1 mutations and had been treated with a CDK4/6i for at least 12 months.

Safety data is consistent with the other endocrine therapies. Most of the adverse events (AEs), including nausea and musculoskeletal pain were grade 1 and 2. No hematological safety signal was observed and none of the patients in either of the two treatment arms had sinus bradycardia.

“Advanced or metastatic ER+, HER2- breast cancer pre-treated with endocrine-based therapy remains an area of unmet medical need. The last endocrine therapy approved was about 20 years ago, and effective endocrine options for this patient population are needed,” said Dr. Aditya Bardia, MD, MPH, Director of Breast Cancer Research at Mass General Cancer Center, Associate Professor at the Medicine Department at Harvard Medical School, and Principal Investigator for the EMERALD trial. “ESR1 mutations are a known driver of resistance to standard endocrine therapy, and so far, have been difficult to treat. The approval of elacestrant is welcomed as it offers a novel option for patients with ER+, HER2- metastatic breast cancer. This therapy targets the ESR1 mutations in metastatic breast cancer and provides patients with a convenient oral once-daily dose.”

“Each year 300,000 Americans are diagnosed with breast cancer and metastatic breast cancer causes the vast majority of deaths from the disease: more than 43,000 annually. We urgently need new and better treatment options to extend and improve the lives of people with metastatic breast cancer,” said Sonya Negley, Executive Director, Metavivor. “We are thrilled to see the approval of ORSERDU, a new oral endocrine therapy, for patients who have tumors that harbor ESR1 mutations, which are present in up to 40% of ER+, HER2- advanced or metastatic breast cancer. We advise patients to get tested for ESR1 mutations at progression in their metastatic treatment, so that their healthcare team can identify the right treatment options for their disease.“

ORSERDU will soon be available in the United States.  Stemline is committed to helping patients access ORSERDU and will be offering services to overcome access barriers. Stemline ARC, a patient support program is available to help guide eligible patients through the various aspects of getting started on treatment, from providing educational information to helping them understand their insurance coverage and identifying potential financial assistance options. For more information, patients and healthcare professionals can call 1-833-4-STEMLINE (1-833-478-3654).

The Menarini Group obtained global licensing rights for elacestrant in July 2020 from Radius Health, Inc., who conducted the EMERALD study. With this approval, Radius will receive milestone payments and royalties from commercial sales. The Menarini Group is now fully responsible for global registration, commercialization, and further development activities for elacestrant.

About EMERALD Phase 3 Study (NCT03778931)
The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. 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 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.

About ORSERDU (elacestrant)
The U.S. Food and Drug Administration (FDA) has approved ORSERDU for the treatment of postmenopausal women or adult men, with ER+, HER2-, ESR1-mutated, advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. The Marketing Authorization Application (MAA) is currently under review by the European Medicines Agency (EMA).

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); ELONA (NCT05618613); ELCIN (NCT05596409). Elacestrant is also planned to be evaluated in early breast cancer disease.

Full prescribing information can be found at www.orserdu.com

Important Safety Information

Warning and Precautions

Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively.  Monitor lipid profile prior to starting and periodically while taking ORSERDU.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman.  Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the final dose.

Adverse Reactions

Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).

The most common adverse reactions (>10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite(15%), diarrhea(13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%).

Drug interactions

Concomitant use with CYP3A4 Inducers and/or inhibitors:  Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU.

Use in specific populations

Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.

Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B).

The safety and effectiveness of ORSERDU in pediatric patients have not been established.

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Indication

ORSERDU (elacestrant), 345 mg tablets, is 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 following at least one line of endocrine therapy.

For more information, please see the full Prescribing Information for ORSERDU here

About The Menarini Group
The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini’s products are available in 140 countries worldwide. For further information, please visit www.menarini.com.

About Stemline
Stemline Therapeutics, a wholly-owned subsidiary of the Menarini Group, is a commercial-
stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics. Stemline commercializes Elzonris®, a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare hematologic cancer, in the United States and Europe, the only approved treatment for BPDCN in the US and EU to date. Stemline also commercializes Nexpovio® in Europe, an XPO1 inhibitor for multiple myeloma originating from a licensing deal with Karyopharm. Stemline has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers.

Media Relations:

The Menarini Group Valeria Speroni Cardi Email: pressoffice@menarini.com

Stemline Therapeutics, Inc. Cheya Pope Email: cpope@stemline.com

Carrick to execute Phase 2 clinical trial in patients with CDK4/6i resistant HR+, HER2- metastatic breast cancer

 

(DUBLIN, Ireland and FLORENCE, Italy, December 19, 2022) - Carrick Therapeutics, an oncology-focused biopharmaceutical company discovering and developing highly differentiated therapies, and the Menarini Group ("Menarini"), a privately-held, leading international pharmaceutical company, today announced a clinical trial collaboration and supply agreement.

This agreement covers the execution of a Phase 2 clinical trial to evaluate the novel combination of Carrick’s samuraciclib (CT7001), an oral and first-in-class inhibitor of CDK7, and Menarini‘s oral selective estrogen receptor degrader (SERD), elacestrant, in patients with CDK4/6i resistant HR+, HER2- metastatic breast cancer. Menarini and Carrick will jointly sponsor the clinical trial.

“We are excited to initiate this collaboration with Menarini to explore the potential of samuraciclib in combination with elacestrant for the treatment of advanced breast cancer,” said Tim Pearson, Chief Executive Officer of Carrick Therapeutics. “Our pre-clinical work and prior clinical studies have validated the biology for SERD combinations with CDK7, pointing to potential synergies when combining samuraciclib with Menarini’s oral SERD, elacestrant. This collaboration represents a shared commitment to maximizing the potential of novel combination therapies to improve outcomes for people living with breast cancer.”

“This new clinical collaboration with Carrick Therapeutics is yet another step we are making to develop elacestrant in an extensive way to address unmet needs of patients resistant to CDK4/6 therapies in HR+, HER2- metastatic breast cancer,” said Elcin Barker Ergun, Chief Executive Officer of Menarini. “Menarini will continue to pursue research collaborations that have the potential to improve patients’ lives in breast cancer.” 

Carrick anticipates initiating the Phase 2 clinical trial in 2023. This new study will expand Carrick’s portfolio of ongoing clinical trials with samuraciclib. The company presented encouraging results from a clinical study combining samuraciclib with fulvestrant at the 2021 San Antonio Breast Cancer Symposium.

 

About The Menarini Group

The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini’s products are available in 140 countries worldwide. For further information, please visit www.menarini.com.

 

About Elacestrant (RAD1901) and the EMERALD Phase 3 Study

Elacestrant is an investigational selective estrogen receptor degrader (SERD). In 2018, elacestrant received Fast Track designation from the FDA. Preclinical studies completed prior to EMERALD indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. The study enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK 4/6 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. Secondary endpoints included evaluation of overall survival (OS), objective response rate (ORR), and duration of response (DOR) and safety.

 

About Samuraciclib (CT7001)

Samuraciclib is the most advanced CDK7 inhibitor in clinical development. Inhibiting CDK7 is a promising therapeutic strategy in cancer as CDK7 regulates the transcription of cancer-causing genes, promotes uncontrolled cell cycle progression and resistance to anti-hormone therapy. Samuraciclib has demonstrated a favorable safety profile and encouraging efficacy in early clinical studies. In addition to the above studies, it is currently being evaluated in prostate cancer with further potential in pancreatic, ovarian and colorectal cancers. Samuraciclib has been granted Fast Track designations from the U.S. Food and Drug Administration (FDA) for use in combination with fulvestrant for the treatment of CDK4/6i resistant HR+, HER2- advanced breast cancer. Carrick is also collaborating with Roche to evaluate a novel combination of samuraciclib and Roche’s oral SERD giredestrant in CDK4/6i resistant HR+, HER2- metastatic breast cancer.  Carrick also intends to evaluate samuraciclib for the treatment of prostate cancer, where CDK7 has been shown to act as a regulator of transcription, the cell cycle and androgen receptor signalling.

 

About Carrick Therapeutics

Carrick Therapeutics is an oncology-focused biopharmaceutical company leveraging its deep expertise to identify and develop highly differentiated novel therapies that address significant unmet needs.  In addition to samuraciclib, Carrick is also developing a novel CDK12/13 inhibitor / Cyclin-K glue-degrader which has advanced into IND enabling toxicology studies.

 

For more information about Carrick Therapeutics, please visit www.carricktherapeutics.com

 

Carrick Contacts
Carrick Therapeutics
Jenny Horsfield, Chief Business Officer
jenny.horsfield@carricktherapeutics.com

Investors and Media
Kevin Lui, Real Chemistry
klui@realchemistry.com

Menarini Contacts
The Menarini Group
Valeria Speroni Cardi, Global Director of Press and Media Relations
pressoffice@menarini.com

• Elacestrant demonstrated longer progression-free survival (PFS) vs SOC endocrine therapy with medians up to 8.6 months, positively associated with the duration of prior treatment with CDK4/6 inhibitors
• Elacestrant side effects were manageable and consistent with previously reported results
• Results demonstrate that elacestrant may have the potential to become a new standard of care as a monotherapy endocrine sequencing option in ER+, HER2- advanced or metastatic breast cancer after progression on CDK4/6i

FLORENCE, Italy, November 30th, 2022 - The Menarini Group (“Menarini”), a privately held Italian pharmaceutical and diagnostics company, and Stemline Therapeutics (“Stemline”), a wholly-owned subsidiary of the Menarini Group, will present additional data from the Phase 3 EMERALD study (NCT03778931) of elacestrant, an investigational oral SERD, during the upcoming San Antonio Breast Cancer Symposium (SABCS) being held from December 6-10.

EMERALD is a Phase 3 registrational trial that demonstrated statistically significant progression-free survival (PFS) with elacestrant vs SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane), meeting both primary endpoints in all patients and in those patients harbouring ESR1 mutations (ESR1-mut), following progression on prior CDK4/6 inhibitors (CDK4/6i) in ER+, HER2- advanced or metastatic breast cancer.

A post-hoc analysis of the PFS results in the EMERALD trial based on the duration of prior CDK4/6i usage shows clinically meaningful results which favor monotherapy elacestrant, both in the total patient population as well as in patients with ESR1-mut. Increased duration of prior CDK4/6i in metastatic patients was positively associated with longer PFS on elacestrant but not with SOC.

For those who were exposed to CDK4/6i ≥12 months prior to randomization on EMERALD, elacestrant achieved:

• In the all-patient population, a mPFS of 3.8 months on elacestrant vs 1.9 months on SOC, a 39% reduction in the risk of progression or death (HR=0.61 95% CI: 0.45-0.83)
• In the ESR1-mut population, a mPFS of 8.6 months on elacestrant vs 1.9 months on SOC, a 59% reduction in the risk of progression or death (HR=0.41 95% CI: 0.26-0.63)

For those who were exposed with CDK4/6i ≥18 months prior to randomization on EMERALD, elacestrant achieved:

• In the all-patient population, a mPFS of 5.5 months on elacestrant vs 3.3 months with SOC, a 30% reduction in the risk of progression or death (HR=0.70 95% CI: 0.48-1.02)
• In the ESR1-mut population, a mPFS of 8.6 months on elacestrant vs 2.1 months on SOC, a 53% reduction in the risk of progression or death (HR=0.47 CI: 0.20-0.79).

Updated safety data were consistent with previously reported results. Most of the adverse events (AEs), including nausea, were grade 1 and 2, and only 3.4% and 0.9% of the patients discontinued trial therapy because of an AE on elacestrant and SOC, respectively. A low percentage of patients received an antiemetic; 8.0% on elacestrant, 3.7% on fulvestrant, and 10.3% on AI, respectively. No hematological safety signal was observed and none of the patients in either of the two treatment arms had sinus bradycardia.

Virginia Kaklamani, MD, DSc, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center, commented, “These results show that when used as a single agent, elacestrant provided mPFS up to 8.6 months, based on the duration of previous CDK4/6 inhibitor therapy, with a manageable safety profile and the convenience of an oral tablet. This suggests elacestrant may have the potential to become a new standard of care as a monotherapy endocrine sequencing option in ER+, HER2- advanced breast cancer after progression on CDK4/6i, before moving to combination therapies.”

“These results further highlight elacestrant’s potential to change the treatment paradigm of ER+, HER2- advanced or metastatic breast cancer. Elacestrant is under Priority Review with the U.S. Food and Drug Administration (FDA) with a target PDUFA date of February 17, 2023,” commented Elcin Barker Ergun, Chief Executive Officer of the Menarini Group.

A complete list of key Menarini Group presentations at SABCS is below.

Lead Author Name	Abstract Number and Title	Presentation Details
V. Kaklamani	GS3-01. 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	December 8, 2022 8:30-8:45 AM CT Oral Presentation General Session 3 Hall 3
H. Rugo	OT2-01-03. ELEVATE: A Phase 1b/2, open-label, umbrella study evaluating elacestrant in various combinations in women and men with metastatic breast cancer (mBC)	December 7, 2022 5:00-6:30 PM CT Ongoing Trials Poster Session 2 Hall 1
M. Piccart	PD18-05. MEN1611, a PI3K Inhibitor, combined with trastuzumab (T) ± fulvestrant (F) for HER2+/PIK3CA mutant (mut) advanced or metastatic (a/m) breast cancer (BC): updated safety and efficacy results from the ongoing Phase 1b study (B-PRECISE-01)	December 9, 2022 7:00-8:15 AM CT Spotlight Poster Discussion 18 Stars at Night Ballroom - Hall 3&4

The Menarini Group obtained global licensing rights for elacestrant in July 2020 from Radius Health, Inc., who conducted and successfully completed the EMERALD study. The Menarini Group is now fully responsible for global registration, commercialization, and further development activities for elacestrant.

About Elacestrant (RAD1901) and the EMERALD Phase 3 Study

Elacestrant is an investigational selective estrogen receptor degrader (SERD). In 2018, elacestrant received Fast Track designation from the FDA. Preclinical studies completed prior to EMERALD indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. The study enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK 4/6 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. Secondary endpoints included evaluation of overall survival (OS), objective response rate (ORR), and duration of response (DOR) and safety.

About The Menarini Group

The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini’s products are available in 140 countries worldwide. For further information, please visit www.menarini.com.

About Stemline

Stemline Therapeutics, a wholly owned subsidiary of The Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics. Stemline commercializes a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the United States and Europe which is also being evaluated as monotherapy and in combination with other agents, in additional clinical trials for a variety of other indications. Stemline has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers.

About Radius

Radius is a global biopharmaceutical company focused on addressing unmet medical needs in the areas of bone health and oncology. Radius’ lead product, TYMLOS® (abaloparatide) injection, was approved by the U.S. Food and Drug Administration for the treatment of postmenopausal women with osteoporosis at high risk for fracture. The Radius clinical pipeline includes investigational abaloparatide injection for potential use in the treatment of men with osteoporosis and the investigational drug, elacestrant (RAD1901), for potential use in the treatment of hormone-receptor positive breast cancer out-licensed to Menarini Group.

Media Relations:

The Menarini Group Valeria Speroni Cardi Email: pressoffice@menarini.com

U.S. Media Nick Hennen LaVoieHealthScience Phone: +1 (929) 462-9479 Email: nhennen@lavoiehealthscience.com