Boost For Oral SERDs As Menarini/Radius’ Orserdu Becomes First Approved For Breast Cancer
Following US FDA Approval
Executive Summary
The firms’ Orserdu has won a US thumbs up for the treatment of ESR1-mutated advanced or metastatic breast cancer, marking a positive breakthrough for the challenging SERD drug class.
Menarini Group/Radius Health, Inc.’s oral selective estrogen receptor degrader (SERD) Orserdu has received approval from the US Food and Drug Administration in breast cancer but only for a subset of patients, nevertheless, it is a milestone that analysts say could positively affect the rest of the pipeline.
The drug, which contains the active ingredient elacestrant, was given the green light for postmenopausal women and adult men with ER+/HER2- ESR1-mutated advanced or metastatic breast cancer that has progressed after at least one line of endocrine therapy on 27 January. The FDA also approved the Guardant360 CDx assay, a companion diagnostic used to identify breast cancer patients eligible for treatment with Orserdu.
The Italian firm’s CEO Elcin Barker Ergun told Scrip that Orserdu will be available soon through a specialty distribution network, and "we have strong field teams in place to support sales, medical education, and reimbursement."
The decision came three weeks ahead of the 17 February Prescription Drug User Fee Act date and was based on data from the pivotal EMERALD trial of 478 people with ER+/HER2- advanced or metastatic breast cancer.
EMERALD showed a progression-free survival (PFS) rate at 12 months with elacestrant of 22.32% versus 9.42% with standard of care (fulvestrant or an aromatase inhibitor) in the overall population. This rose to 26.76% versus 8.19% in a sub-population with an ESR1 mutation also included in the study (just over 200 patients).
In the study, the drug achieved a median PFS of 3.8 months versus 1.9 months for the active comparator arm (p=0.0005). An analysis of PFS in the 250 patients without an ESR1 mutation resulted in a hazard ratio of 0.86, suggesting EMERALD success was mostly driven by the ESR1-mutated subgroup.
Safety-wise, adverse events seen at a rate of at least 10% included musculoskeletal pain, nausea, increased cholesterol, fatigue, decreased appetite and vomiting among others. (Also see "Menarini And Radius Skip Into SERD Lead With Elacestrant Success" - Scrip, 21 Oct, 2021.)
Sales projections for Orserdu tend to vary between analysts with those at Biomedtracker touting blockbuster potential while others take a more cautious view, predicting peak sales to taper at around the $420m mark.
While Orserdu had shown a significant benefit in EMERALD all-comers and a broader approval would have opened up a bigger market opportunity, the ESR1 label is reasonable and unsurprising seeing as the mutated subgroup drove the overall results, Jefferies analyst Michael Yee said in a 30 January note.
ESR1 mutations are “very uncommon” in untreated breast cancer patients but occur in approximately one-third of breast cancer patients previously treated with aromatase inhibitors in the metastatic setting, Datamonitor Healthcare analyst Dana Gheorghe told Scrip.
Orserdu’s success should also have a positive read-through to the SERD class more broadly, Yee remarked, as it should drive more ESR1 testing that would benefit future entrants. This is important because the SERD space has faced multiple clinical setbacks over the past year, starting with the Phase II failure of Sanofi’s amcenestrant in March 2022, which led the firm to abandon the asset entirely later than year. (Also see "Sanofi Abandons Oral SERD Breast Cancer Drug As Pipeline Woes Mount" - Scrip, 17 Aug, 2022.)
In April, Roche Holding AG revealed that its asset, giredestrant, had also failed a Phase II study. Notably, neither company had targeted ESR1-mutated patients in their respective trials. (Also see "Roche's SERD Setback Means Menarini Retains An Edge" - Scrip, 25 Apr, 2022.) Despite these hurdles, there are 12 SERD candidates in the clinic for the treatment of breast cancer, according to the Citeline database Pharmaprojects.
One company that is poised to benefit from Orserdu’s success according to Yee is Olema Pharmaceuticals, Inc., whose SERD, OP-1250, is set to enter a Phase III monotherapy trial later this year. Unlike other drugs of its class, OP-1250 can cross the blood-brain barrier and Olema is to trial it in a similar population to that of EMERALD. (Also see "Olema Flies Flag For SERDs, Planning Phase III Trials As Rivals Stumble" - Scrip, 22 Dec, 2022.)
Elsewhere, big pharma-backed Phase III contenders that could soon make their mark include AstraZeneca PLC’s camizestrant and Eli Lilly and Company’s imlunestrant. Camizestrant is under investigation in the Phase III SERENA-6 trial in first-line HR+ metastatic breast cancer patients with ESR1 mutations, with topline data expected in the second half of the year.
Radius Set To Rake In Royalties
Orserdu was originally developed by Radius with Menarini licensing the global development and commercialization rights to the asset for $30m upfront as part of a 2020 deal. Under the terms of that agreement, Radius is eligible to receive tiered low to mid-teen percentage royalties on elacestrant, while Menarini is responsible for global registration, commercialization, and further development activities.