NEW YORK – The National Institute for Health and Care Excellence (NICE) does not recommend Menarini Group's Orserdu (elacestrant) for patients in England with previously treated estrogen receptor (ER)-positive HER2-negative, locally advanced or metastatic breast cancer harboring an activating ESR1 mutation.
However, NICE is accepting comments on its draft guidance before issuing the final guidance and has also asked Menarini for further clarification and analyses of its data on Orserdu.
"The main area of uncertainty the committee had to contend with was the estimates for how long elacestrant stopped the disease from getting worse compared with current clinical practice," Helen Knight, director of health technology evaluation at NICE, said in a statement. She added that the additional analyses and comments will help NICE decide whether in determining the cost effectiveness of Orserdu, it needs to consider a severity modifier, a factor that increases the value of quality-adjusted life years (QALYs) for medicines that treat severe diseases.
Menarini submitted data to NICE from the Phase III EMERALD trial, in which researchers compared Orserdu to physicians' choice of standard hormone therapy including fulvestrant, anastrozole, letrozole, or exemestane. The EMERALD results showed that Orserdu improved median progression-free survival versus standard care in the ESR1-mutant subgroup, 8.6 months and 1.9 months, respectively. In patients with both ESR1 and PIK3CA mutations in the study, Orserdu also improved median progression-free survival compared to standard care, 5.5 months and 1.9 months, respectively.
In its draft guidance, NICE concluded that there was uncertainty about the clinical effectiveness of Orserdu due to the EMERALD trial's comparator arm not reflecting standard treatment for some patients, particularly those with dual ERS1 and PIK3CA mutations who could receive a PI3K inhibitor.
NICE also concluded that the firm's cost-effectiveness measurements for Orserdu were above what the institute considers a cost-effective use of National Health Service resources, falling between £20,000 ($26,559) and £30,000 ($39,838) per QALY gained. However, NICE did not report exact cost-effectiveness figures because of confidential discounts.
NICE is accepting comments on the guidance until Oct. 22 from stakeholders about the evidence and its interpretation of clinical and cost-effectiveness and whether there are any additional aspects that should be considered in its evaluation of Orserdu.
Orserdu was approved in the US in this same indication, as a second-line treatment for ER-positive HER2-negative advanced breast cancer harboring ESR1 mutations, in January 2023. The drug was also approved in this indication in Europe in September 2023.