Imlunestrant

Roche’s giredestrant misses primary endpoint in persevERA trial for ER-positive advanced breast cancer Roche announced that the Phase III persevERA Breast Cancer study evaluating giredestrant in combination with palbociclib did not meet its primary endpoint of a statistically significant improvement in progression-free survival in ER-positive, HER2-negative locally advanced or metastatic breast cancer. The result complicates the trajectory of Roche’s oral selective estrogen receptor degrader (SERD) in the first-line advanced setting, even as the company points to positive Phase III readouts from two other giredestrant trials to sustain its broader development program. The persevERA Breast Cancer study is a Phase III, randomized, double-blind, placebo-controlled, multicenter trial that enrolled 992 patients globally. Participants with ER-positive, HER2-negative locally advanced or metastatic breast cancer were randomized to receive either giredestrant plus palbociclib or letrozole plus palbociclib as first-line treatment. The primary endpoint was investigator-assessed progression-free survival. Key secondary endpoints included overall survival, objective response rate, duration of response, and safety. While the study did not achieve statistical significance on its primary endpoint, Roche reported that a numerical improvement in PFS was observed, though no hazard ratio or p-value were disclosed. Adverse events in the giredestrant arm were described as manageable and consistent with the known safety profiles of each treatment. Full results are expected at an upcoming medical meeting. Despite the miss, Roche signaled continued commitment to giredestrant across multiple settings. The US FDA recently accepted a New Drug Application based on the Phase III evERA study, which showed positive results for giredestrant plus everolimus in previously treated advanced disease. Roche also plans to submit Phase III lidERA data in early-stage adjuvant breast cancer to the US FDA in the coming weeks. A second first-line advanced study, pionERA, evaluating giredestrant with physician’s choice of CDK4/6 inhibitor in endocrine-resistant disease, is expected to read out in 2027. Levi Garraway, Roche’s Chief Medical Officer, stated: “We believe there is a path forward for combining giredestrant with a CDK4/6 inhibitor in the adjuvant setting and we are conducting further studies”. Giredestrant has not received regulatory approval for any indication to date. Giredestrant is an oral SERD and full antagonist designed to block estrogen from binding to ERα and trigger receptor degradation. Unlike fulvestrant, the only approved SERD, giredestrant is orally administered and active against ESR1-mutant forms of the receptor that commonly arise during endocrine resistance. ER-positive breast cancer accounts for approximately 70% of all breast cancer cases, and despite advances with CDK4/6 inhibitors and aromatase inhibitors, up to a third of early-stage patients eventually experience recurrence, while resistance in the advanced setting remains a persistent clinical challenge. The oral SERD class has attracted substantial investment, though clinical setbacks have been common. Key competitors include: Menarini/Stemline’s elacestrant (Orserdu), the first oral SERD approved by the US FDA in 2023 for ESR1-mutated ER-positive metastatic breast cancer. Eli Lilly’s imlunestrant (EMBER-3), an oral SERD that received US FDA approval in early 2026 for ESR1-mutated advanced breast cancer. AstraZeneca’s camizestrant (SERENA program), a next-generation oral SERD in Phase III development for both early and advanced ER-positive breast cancer settings. Earlier stage programs include Accutar Biotechnology’s AC699, palazestrant (Olema Oncology) and vepdegestrant (Arvinas/Pfizer). The persevERA miss narrows the differentiation case for giredestrant in the first-line combination setting, where letrozole plus a CDK4/6 inhibitor remains standard of care. Roche’s strategy now depends on the pending NDA review for evERA, the lidERA adjuvant submission, and the pionERA readout to establish giredestrant’s clinical position across the ER-positive breast cancer treatment continuum. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

Roche’s oral SERD gets December decision deadline from FDATeva's long-acting schizophrenia injection nears FDA finish lineCandel bags $100M to support launch of viral immunotherapyRoche’s oral SERD gets December decision deadline from FDA The FDA on Friday accepted for review an NDA from Roche for its experimental oral selective oestrogen receptor degrader (SERD), giving it a Dec. 18 PDUFA date. The Swiss pharma is seeking giredestrant's approval in combination with everolimus to treat adults with ER-positive, HER2-negative, ESR1-mutated locally advanced or metastatic breast cancer following recurrence or progression on a prior endocrine-based regimen.Giredestrant impressed physicians and investors alike across two back-to-back readouts late last year. At the San Antonio Breast Cancer Symposium (SABCS), Roche reported that the oral SERD significantly reduced the risk of invasive disease recurrence or death by 30% versus standard-of-care endocrine therapy in the specific breast cancer patient population (see – Spotlight On: Interim lidERA success lifts Roche's giredestrant into adjuvant spotlight and raises CDK4/6 inhibitor combo questions).Roche's candidate stands to be the second oral SERD to receive an FDA nod, following approval for Eli Lilly's Inluriyo (imlunestrant) in September; AstraZeneca is also developing its own candidate, camizestrant. The competition between the three pharmas to bring oral SERDs into frontline breast cancer care is a key oncology story FirstWord is watching this year (see – Spotlight On: Five key oncology stories to watch in 2026).-Elizabeth EatonTeva's long-acting schizophrenia injection nears FDA finish lineThe FDA is reviewing a marketing application for Teva's experimental schizophrenia treatment, the company said Friday. TEV-'749 is a long-acting formulation of the atypical antipsychotic olanzapine, designed to improve treatment adherence and help patients maintain long-term stability.According to Teva, other long-acting versions of the therapy carry a risk of post-injection delirium/sedation syndrome; Eli Lilly currently markets olanzapine in a once-daily oral formulation as Zyprexa.The Israeli drugmaker's submission is based on data from the Phase III SOLARIS study, which showed that TEV-'749 led to a clinically meaningful and statistically significant change in the Positive and Negative Syndrome Scale total score compared to placebo.If the FDA approves Teva's extended-release injectable formulation of olanzapine, Royalty Pharma will receive low- to mid-single digit royalties, per an agreement signed in 2023 under which it provided Teva with up to $125 million in development funding for the candidate. -Elizabeth EatonCandel bags $100M to support launch of viral immunotherapyCandel Therapeutics inked a $100-million royalty funding agreement with RTW Investments, contingent on the FDA approval of the former's lead asset aglatimagene besadenovec (CAN-2409) — a viral immunotherapy for intermediate- to high-risk localised prostate cancer."This non-dilutive strategic financing will support the US launch of aglatimagene besadenovec…and will allow us to further invest in what we believe will be a world-class commercial programme," said Paul Peter Tak, chief executive of Candel.Backed by favourable disease-free survival data in a pivotal prostate cancer study, the biotech plans to submit a marketing application to the US regulator in the fourth quarter. Upon FDA approval of the therapy, RTW is eligible for a tiered, capped single-digit royalty on annual net US sales. -Pavan Kamat