Elacestrant hydrochloride

Roche’s breast cancer pill giredestrant is the first member of its class — the selective estrogen receptor degraders, or SERDs — to prove itself effective in patients who do not have a mutated version of the receptor that these drugs target. The findings, which are set to be presented Saturday at the European Society for Medical Oncology’s annual meeting in Berlin, could give Roche’s pill an advantage against the SERD pills on the market, including Eli Lilly’s newly approved Inluriyo and Menarini’s Orserdu. Those drugs have only been shown to work in patients with mutations in the gene for the ESR1 receptor, which SERDs are designed to inactivate. In non-mutated patients, giredestrant yielded a 16% decrease in the risk of death or disease progression versus standard of care, Roche’s head of oncology and hematology product development Charlie Fuchs told Endpoints News before the presentation. The data came from the Phase 3 evERA trial . In mutated patients, the risk of disease progression or death was cut by 62% versus control. And in the overall trial population, which is also called the intent-to-treat population, the risk was reduced by 44%, which Fuchs describes as “pretty meaningful.” Around 55% of the patients in the trial had ESR1 mutations, he said. Roche intends to seek approval for the drug, but Fuchs declined to provide specifics about timing. In the overall population, median progression-free survival was 8.8 months in the giredestrant arm compared with 5.5 months with standard care. The difference was statistically significant, with a p-value of less than 0.0001. In the ESR1-mutated population, median PFS was 9.99 months versus 5.5 months with control — that’s also good for significance, with a similar p-value. “To our knowledge, [no one has] shown what we think is a clinically meaningful and significant benefit in the intent-to-treat population,” Fuchs said. “In terms of a compelling body of evidence supporting both mutants and intent-to-treat, I think this study is unique.” The trial continues, with the aim of also proving a benefit in overall survival. The data presented at ESMO showed that the drug reduced the risk of death by 31% and 38% in the overall and mutant populations versus control, but neither arm has hit significance yet. “Overall survival is still very immature,” Fuchs said, “but we’re seeing a really encouraging, positive trend in overall survival, both in the mutants and the non-mutants.” Fuchs said the non-mutant patients given giredestrant also saw improvements in secondary endpoints, including objective response rate and duration of response. The objective response rate was 20.0% in non-mutant patients given the SERD, versus 8.7% for non-mutant patients in the control arm. The company believes this drives clinical benefit, he said. Median duration of response was also longer, at 12.7 months for giredestrant recipients and 7.7 months for those who received standard of care. “We think the benefit of giredestrant is driven by both populations — somewhat differentially, as might be expected — but both, we think, are clinically meaningful,” Fuchs said. Roche described the SERD’s side effects as “manageable,” with no new safety signals or ocular toxicity. Patients in the evERA trial took giredestrant in combination with a generic antiproliferative, with the control arm patients taking everolimus plus endocrine therapy. The patients had estrogen receptor-positive, HER2-negative, locally advanced or metastatic breast cancer, and had been treated with CDK4/6 inhibitors and hormone therapy. Treatment with CDK4/6 inhibitors can induce ESR1 mutations. How much of an advantage giredestrant might have over its competitors remains to be seen. But Fuchs is confident. “We think the drug is differentiated compared to the other drugs in development,” he said. “What we can say is it’s the most potent SERD currently.”

A regimen combining a new experimental Roche medicine with an older drug lowered the risk of disease progression or death by nearly two thirds in people with a certain type of breast tumor, according to study data revealed Saturday.Roche disclosed last month that the closely watched Phase 3 study had succeeded, but presented details for the first time on Saturday at the European Society for Medical Oncology meeting in Berlin. The data, should it lead to a regulatory approval, could help distinguish the company's medicine from others like it. These drugs collectively known as selective estrogen receptor degraders, or SERDs are newer, oral versions of a decades-old treatment widely used against breast cancer. Two of them, Eli Lillys Inluriyo and Menarini Groups Orserdu, are already available.Roche's giredestrant and its peers have been evaluated against “ER-positive, HER2-negative“ breast cancer, the most common form of the disease. That form is first treated with hormone drugs and a type of targeted therapy called a CDK4/6 inhibitor. Many patients progress, though, and afterwards, the options are more limited. Over the last two years, Orserdu and Inluriyo have increased those options. In testing, theyve proven effective in people whose ER-positive, HER2-negative tumors progress and have a mutations to a gene called ESR1 an alteration that occurs during or after exposure to hormone therapy. Orserdu, for example, was associated with a 45% reduction in the risk of disease progression or death compared to hormone therapy, while Inluriyo posted a 38% risk reduction.Roche is the latest to read out results. In its trial, named evERA, Roche combined giredestrant with everolimus, a drug sold under the brand name Afinitor and used in second-line, ER-positive disease. The trial tested that combination against older hormone treatments and everolimus, measuring its ability to hold disease in check among those with ESR1 mutations as well as the overall study population.The results presented Saturday show the giredestrant combination reduced the risk of progression in the ESR1-positive population by 62% and in the broader group by 44%. An exploratory analysis of only those without ESR1 mutations which wasnt as statistically robust as the other findings showed no significant difference in the risk of disease progression between people who got giredestrant or other hormone therapies, according to lead study investigator Erica Mayer, an oncologist at Dana-Farber Cancer Institute.However, Mayer noted the analysis did show signs of a benefit on response rates, the length of those responses, and patient survival. The totality of the data supports the improvement seen in the [broad] population in the trial, she said. I think the majority of medical oncologists feel that the optimal treatment after a CDK [inhibitor] is endocrine therapy plus a targeted partner, Mayer said. Id be very excited to use this regimen in clinic with patients.While trials are often difficult to directly compare, Inluriyo didnt delay progression in the broad group of ESR1-positive and negative enrollees in the pivotal study underlying its approval. Orserdu did, reducing the risk of progression by 30%, but still wasnt cleared for non-ESR1 patients because the benefit was primarily attributed to results from patients in the ESR1-[positive] subgroup, FDA reviewers wrote.Inluriyo hasnt been on the market long enough for Lilly to report quarterly sales. And as a private company, Menarin doesnt publicly report earnings. But a drug royalty company called DRI Healthcare has acquired twice pieces of Orserdu sales, first buying into a mid-single digit percentage of royalties and then a low to high single-digit royalty stream. Last year, the first piece generated $28.4 million for DRI and the second earned $37.1 million. '