Benzinga | Dec 8, 2021 10:20AM EST

Radius Health Highlights EMERALD Trial Results For Elacestrant Presented At San Antonio Breast Cancer Symposium: Trial Met Both Primary Endpoints

* 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

FLORENCE, Italy and BOSTON, Dec. 08, 2021 (GLOBE NEWSWIRE) -- 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.