PR96106

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

FLORENCE, Italy and BOSTON, May 20, 2022 /PRNewswire=KYODO JBN/ --

-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

    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. [

https://ascopubs.org/doi/full/10.1200/JCO.22.00338 ] 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.

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    Source: Menarini Industrie Farmaceutiche Riunite