PR93568

FLORENCE, Italy and BOSTON, Dec. 8, 2021 /PRNewswire＝KYODO JBN/ --

- Trial met both primary endpoints demonstrating statistically significant and

clinically meaningful extension of progression free survival (PFS) as

monotherapy vs. standard of care (SoC) endocrine therapy in overall population

and estrogen receptor mutation (mESR1) population

- In the overall population, elacestrant reduced risk of progression or death

by 30% vs. SoC

- In the mESR1 population, elacestrant reduced risk of progression or death by

45% vs. SoC

- PFS rate at 12 months with elacestrant was 22.32% versus 9.42% with SoC in

the overall population, and 26.76% versus 8.19% in the mESR1 population

- Compared to fulvestrant, elacestrant demonstrated statistically significant

PFS and reduced the risk of progression or death by 32% in the overall

population and 50% in the mESR1 population

- With these results, elacestrant became the first oral SERD to demonstrate

higher efficacy than fulvestrant in a pivotal trial

- Elacestrant was well tolerated and can become standard of care in this

patient population

The Menarini Group ("Menarini") and Radius Health, Inc. ("Radius") (NASDAQ:

RDUS) (collectively, the "Companies") provided details on the elacestrant data

from the EMERALD trial following the positive results presented today at the

San Antonio Breast Cancer Symposium (SABCS). The data was presented as a "Late

Breaker" and shared in an oral presentation by Dr. Aditya Bardia, MD.

The EMERALD trial (NCT03778931), a multicenter, international, randomized,

open-label, controlled phase 3 trial evaluated elacestrant as a monotherapy

versus SoC for the treatment of ER+/HER2- advanced or mBC. The trial enrolled

patients who had received 1 or 2 prior lines of endocrine therapy (ET). Prior

progression on an ET plus CDK4/6 inhibitors was mandated for all patients. Up

to 1 line of chemotherapy was allowed.

EMERALD met its two primary endpoints: progression-free survival in the overall

population and PFS in patients with tumors harboring Estrogen Receptor 1

mutations.

Dr. Aditya Bardia, MD, breast medical oncologist at Mass General Cancer Center,

Harvard Medical School and principal investigator of EMERALD, commented,

"Patients with pre-treated ER+/HER2- advanced or metastatic breast cancer

currently have limited treatment options due to the development of endocrine

therapy resistance from earlier treatment lines." Dr. Bardia continued,

"Elacestrant – as the first oral SERD – has the potential to become the new

standard of care given its performance vs. intramuscular fulvestrant and SoC in

the overall population and in the ESR1 patient subgroup. As an oral

monotherapy, elacestrant will offer patients, their families, and healthcare

providers an efficacious and safe treatment option going forward."

Elcin Barker Ergun, Chief Executive Officer of the Menarini Group, commented,

"We are extremely pleased with the results from the EMERALD study. The data

appears to demonstrate that elacestrant can create a well tolerated,

efficacious oral option vs. fulvestrant and SoC in 2/3 line for patients

suffering from advanced or metastatic breast cancer, including those patients

with a tumor harboring ESR1 mutations, one of the most difficult to treat

subgroups in such cancers. We plan to proceed with regulatory submissions in

the United States and European Union in 2022 given the positive safety and

efficacy results and thank all patients, their families and healthcare

professionals for participating in this important clinical trial."

Menarini plans to pursue combination studies and initiate activity in new lines

of therapy such as the adjuvant setting, enabling elacestrant to be utilized in

fully addressing the highest unmet needs for ER+/HER2-patients. In 2018,

elacestrant received fast track designation from the FDA.

Trial Results:

All patients were mandated to be treated with CDK 4/6 inhibitors. Moreover,

patient population characteristics showed that 69.4% of patients had visceral

metastasis and 22.2% received chemotherapy. EMERALD met both primary endpoints,

which measured PFS of elacestrant as a monotherapy vs. SoC in the overall and

mESR1 populations:

- Overall Population

- Reduced risk of progression or death vs. SoC by 30% (HR=0.697 [95% CI:

0.552, 0.880]; P=0.0018)

- Extended median PFS by 2.79 months versus SoC of 1.91

- At 12 months, probability of PFS was 22.3% (95% CI: 15.2%, 29.4%) with

elacestrant vs. 9.4% (95% CI: 4.0%, 14.8%) with SoC

- Compared to fulvestrant, elacestrant reduced risk of progression or death by

32% (HR=0.684 [95% CI: 0.521, 0.897]; P=0.0049)

- ESR1 Mutation Population

- Reduced risk of progression or death versus SoC by 45% (HR=0.546 [95% CI:

0.387, 0.768]; P=0.0005)

- Extended median PFS by 3.78 months versus SoC of 1.87

- At 12 months, probability of PFS was 26.8% (95% CI: 16.2%, 37.4%) with

elacestrant vs. 8.2% (95% CI: 1.3%, 15.1%) with SoC

- Compared to fulvestrant, elacestrant reduced the risk of progression or

death by 50% (HR=0.504 [95% CI: 0.341, 0.741]; P=0.0005)

- In both patient populations, results in key pre-specified subgroups,

including visceral metastases, number of prior lines, and geographical region,

were consistent with the overall outcome

A key secondary endpoint for the EMERALD trial is Overall Survival (OS). A pre

specified interim analysis indicates a trend favoring elacestrant over SoC in

both patient groups. Final analysis is expected to occur in late 2022 or early

2023.

Safety Results:

Elacestrant was well tolerated with an encouraging safety profile consistent

with other ETs:

- TEAEs leading to discontinuation: infrequent in both elacestrant and SoC arms

(6.3% and 4.4%)

- Grade 3 and higher TRAE were 7.2% for elacestrant and 3.1% for SoC

- Grade 3 and higher adverse events for elacestrant: nausea, vomiting and

diarrhea were 2.5%, 0.8% and 0%, respectively

A detailed evaluation of data is ongoing and additional results are expected to

be published in a peer-reviewed journal.

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. 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 cyclin-dependent kinase (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 is progression-free survival (PFS) in the overall patient population

and in patients with estrogen receptor 1 gene (ESR1) mutations. Secondary

endpoints include evaluation of overall survival (OS), objective response rate

(ORR), and duration of response (DOR).

About Menarini

The Menarini Group is a leading international pharmaceutical and diagnostics

company, with a turnover of $4.2 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 10

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's 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

endocrine and metabolic orphan diseases, initially targeting Prader-Willi

Syndrome.

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 timing of publication of the EMERALD Phase 3

topline results; 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, 2020 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