Menarini Group and Radius Health, Inc. announce publication of elacestrant pivotal Phase 3 EMERALD clinical trial data in the Journal of Clinical Oncology

• Emerald study met both its primary end points of Progression-free survival (PFS) in overall population and in ESR1 mutated patients
• PFS rate at 12 months with elacestrant was 22.32% vs. 9.42% with SOC in the overall population, and 26.76% vs. 8.19% in the ESR1 mutation population
• Data demonstrated elacestrant significantly reduced the risk of disease progression or death by 30% in all patients and by 45% in patients with ESR1 mutation
• Compared with fulvestrant, elacestrant demonstrated statistically significant PFS and reduced the risk of progression or death by 32% in the overall population and 50% in the ESR1 mutation population

FLORENCE, Italy and BOSTON, May 20, 2022 /CNW/ -- The Menarini Group ("Menarini") and Radius Health, Inc. ("Radius") (NASDAQ: RDUS) (collectively, the "Companies") today announced that data from the pivotal phase 3 EMERALD clinical trial (NCT03778931) evaluating elacestrant as a monotherapy vs. standard of care (SOC; fulvestrant or aromatase inhibitor, AI) for the treatment of ER+/HER2- advanced or metastatic breast cancer were published in the Journal of Clinical Oncology.¹ Elacestrant is the first oral selective estrogen receptor degrader (SERD) demonstrating a significant improvement in PFS vs. SOC with manageable safety in a phase 3 trial for patients with ER-positive/HER2-negative advanced breast cancer.

Dr. Aditya Bardia, breast medical oncologist and director of Breast Cancer Research at Mass General Cancer Center, Harvard Medical School and principal investigator of the EMERALD clinical trial, commented, "There is an urgent unmet need for oral SERDs that are safe and effective against ER-positive metastatic breast cancer after progression on earlier lines of therapy, including CDK4/6 inhibitors. EMERALD is the first study to demonstrate a significant improvement in clinical outcomes with elacestrant, an oral SERD monotherapy, versus standard of care in a randomized, global phase III study for patients with ER-positive/HER2-negative advanced breast cancer. Further research is needed to develop combination therapies as well as evaluate novel endocrine therapies for patients with early breast cancer."

As reported in the Journal of Clinical Oncology:

Patients had disease progression during or within 1 month following 1 or 2 lines of endocrine therapy and a cyclin-dependent kinase (CDK) 4/6 inhibitor. Patients could also have received 1 line of chemotherapy.

• 43% received 2 prior endocrine therapies for advanced breast cancer
• 22% received chemotherapy for advanced breast cancer
• 48% had detectable ESR1 mutation

Patients were randomized 1:1 to elacestrant (400 mg orally daily) or SOC choice of fulvestrant or AI; the protocol recommended that patients previously treated with fulvestrant receive AI and patients previously treated with AI receive fulvestrant.

Among the 477 patients enrolled in the trial, 239 received elacestrant.

Of the 165 patients who received fulvestrant all were pretreated with AI during the treatment for metastatic disease except n=6 who received fulvestrant. Of the 73 who received AI all were pretreated with fulvestrant except n=4.

Primary endpoints were PFS by blinded independent central review (IRC) in all patients and patients with detectable ESR1 mutations.

Elacestrant significantly reduced the risk of disease progression or death by 30% in all patients and by 45% in patients with ESR1 mutation.

• PFS was prolonged in all patients (HR=0.70; 95% CI, 0.55–0.88; P=0.0018)
• PFS was prolonged in patients with ESR1 mutation (HR=0.55; 95% CI, 0.39–0.77; P=0.0005)

PFS rate at 12 months with elacestrant was 22.3% vs. 9.4% with SOC in the overall population, and 26.8% vs. 8.2% in the ESR1 mutation population

The most common treatment emergent adverse events (AEs) in patients receiving elacestrant were mild or moderate gastrointestinal events.

Nausea was the most common AE.

• Any severity: 35% of patients receiving elacestrant and 16% fulvestrant, 25% receiving AI
• Severe (grade 3 or 4): 2.5% of patients receiving elacestrant and 0.9% receiving SOC

Treatment-related grade 3/4 AEs occurred in 7.2% of patients receiving elacestrant and 3.1% receiving SOC. Treatment was discontinued due to a treatment-related AEs in 3.4% receiving elacestrant and 0.9% receiving SOC.

A subgroup analysis of patients with no prior chemotherapy in EMERALD will be presented at ASCO 2022 (Abstract: 1100)

Menarini plans to pursue combination studies and study the potential of elacestrant to be effective in addressing the highest unmet needs for ER+/HER2-patients.

About Elacestrant (RAD1901) and EMERALD Phase 3 Study

Elacestrant is a selective estrogen receptor degrader (SERD), out-licensed to Menarini Group, which is being evaluated for potential use as a once daily oral treatment in patients with ER+/ HER2- advanced breast cancer. 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 477 patients who have 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 endpoint of the study was 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).

References

1.  Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022 May 18:JCO2200338. doi.org: 10.1200/JCO.22.00338. Epub ahead of print.

About Menarini

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 Radius

Radius is a global biopharmaceutical company focused on addressing unmet medical needs in the areas of bone health, orphan diseases, 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; an investigational abaloparatide transdermal system for potential use in the treatment of postmenopausal women with osteoporosis; the investigational drug, elacestrant (RAD1901), for potential use in the treatment of hormone-receptor positive breast cancer out-licensed to Menarini Group; and the investigational drug RAD011, a synthetic cannabidiol oral solution with potential utilization in multiple neuro-endocrine, neurodevelopmental, or neuropsychiatric disease areas, initially targeting Prader-Willi syndrome, Angelman syndrome, and infantile spasms.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the expected regulatory submissions in the United States and European Union; and ongoing clinical development activities with respect to elacestrant.

These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the adverse impact the ongoing COVID-19 pandemic is having and is expected to continue to have on our business, financial condition and results of operations, including our commercial operations and sales, clinical trials, preclinical studies, and employees; quarterly fluctuation in our financial results; our dependence on the success of TYMLOS, and our inability to ensure that TYMLOS will obtain regulatory approval outside the U.S. or be successfully commercialized in any market in which it is approved, including as a result of risk related to coverage, pricing and reimbursement; risks related to competitive products; risks related to our ability to successfully enter into collaboration, partnership, license or similar agreements; risks related to clinical trials, including our reliance on third parties to conduct key portions of our clinical trials and uncertainty that the results of those trials will support our product candidate claims; the risk that adverse side effects will be identified during the development of our product candidates or during commercialization, if approved; risks related to manufacturing, supply and distribution; and the risk of litigation or other challenges regarding our intellectual property rights. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, or SEC, including under the caption "Risk Factors" in our Annual Report on Form 10-K for the year ending December 31, 2021 and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

SOURCE Menarini Industrie Farmaceutiche Riunite

Investor & Media Relations Contacts: Menarini: Valeria Speroni Cardi, Email: [email protected] | Radius: Ethan Holdaway, Email: [email protected], Phone: [phone]