FDA delays decision on AstraZeneca's camizestrant after ODAC reverse

AstraZeneca (LSE/STO/NYSE: AZN) has disclosed that the US FDA has extended the Prescription Drug User Fee Act (PDUFA) date for the New Drug Application (NDA) for [camizestrant in combination with a CDK4/6 inhibitor](https://news.cision.com/astrazeneca/r/us-fda-decision-date-on-camizestrant-extended,c4353645), seeking first-line approval in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumours carry an emergent ESR1 mutation. The extension follows a request by the FDA for additional analyses to support its review. The FDA had previously granted Breakthrough Therapy Designation for the camizestrant combination in this setting in May 2025. However,[ in April 2026](https://allsci.com/press-release/fdas-odac-votes-against-astrazenecas-camizestrant-combo-in-breast-cancer/), the agency's Oncologic Drugs Advisory Committee did not reach a majority vote in favour of the benefit of switching to camizestrant plus a CDK4/6 inhibitor upon detection of an ESR1 mutation in ctDNA prior to radiographic progression, a decision that preceded the current request for additional data. The NDA, which covers camizestrant used alongside palbociclib, ribociclib, or abemaciclib, targets a molecularly defined patient population identified through circulating tumour DNA (ctDNA) testing during first-line treatment. The FDA's extension of the camizestrant PDUFA date was triggered by a request for supplementary data, including ctDNA clearance analyses linked to longer-term efficacy outcomes. AstraZeneca said those data are scheduled for presentation on June 2 at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. No revised PDUFA date was specified in the company's announcement. ## SERENA-6 trial camizestrant data underpinning the application The NDA is supported by the [SERENA-6 Phase III trial](https://app.allsci.com/article/ASC-PB-0000280667529-1.0-1764262676), a double-blind, randomised study enrolling 315 adults with HR-positive, HER2-negative advanced breast cancer who were receiving first-line treatment with an aromatase inhibitor plus a CDK4/6 inhibitor and in whom an ESR1 mutation had emerged on ctDNA testing. Participants were randomised to switch the endocrine backbone to camizestrant or to continue with an aromatase inhibitor, in both cases alongside a CDK4/6 inhibitor. The trial met its primary endpoint of investigator-assessed progression-free survival (PFS). Camizestrant reduced the risk of disease progression or death by 56% compared with continuing aromatase inhibitor therapy (HR 0.44; 95% CI 0.31–0.60; p \< 0.00001), with median PFS of 16.0 months versus 9.2 months. Sustained disease control at 24 months was observed in 29.7% of patients in the camizestrant arm compared with 5.4% in the control arm. Data for the key secondary endpoints of overall survival and time to second disease progression (PFS2) were immature at the primary analysis, though PFS2 favoured camizestrant (25.7 months versus 19.1 months; HR 0.63; 95% CI 0.46–0.86; p\=0.00373). Overall survival data showed an HR of 0.87 (95% CI 0.57–1.30) and continued to mature. Results were published in the [New England Journal of Medicine](https://doi.org/10.1056/NEJMoa2502929) in 2025 and presented at the ASCO Annual Meeting that year. ## Scientific and competitive context Camizestrant is an oral next-generation selective estrogen receptor degrader (SERD) and complete ER antagonist. ESR1 mutations arise in approximately 30% of patients with HR-positive advanced breast cancer during first-line aromatase inhibitor-based treatment, conferring ligand-independent ER activation and reducing the efficacy of continued aromatase inhibitor therapy. The camizestrant AstraZeneca approval filing is premised on a biomarker-guided adaptive strategy — switching the endocrine backbone upon ctDNA-detected ESR1 mutation emergence before radiographic progression — a clinical approach for which no therapy is currently approved. The broader ER-targeting landscape has expanded recently. Eli Lilly's imlunestrant (Inluriyo) received FDA approval in September 2025 for ESR1-mutated ER-positive, HER2-negative advanced breast cancer in the second-line setting. Arvinas and Pfizer's vepdegestrant (Veppanu), the first approved PROTAC, received FDA approval in May 2026 in a comparable post-progression population. Roche's giredestrant, another oral SERD being evaluated in combination with everolimus, has an NDA under FDA review following acceptance in February 2026. Camizestrant is differentiated from these agents by its proposed positioning within the first-line setting, specifically as a mutation-triggered switch rather than a therapy initiated after documented progression. The ODAC's failure to reach a majority vote in April 2026 centred on the question of whether switching endocrine therapy upon ctDNA ESR1 detection — prior to radiographic progression — provides a clinically meaningful benefit. The advisory committee's hesitation reflects a broader methodological debate about surrogate endpoints in adaptive treatment strategies and the evidentiary standard for a pre-progression switch. AstraZeneca's submission of ctDNA clearance data linked to longer-term outcomes represents an attempt to address those concerns directly. Outside the US, the European Medicines Agency's Committee for Medicinal Products for Human Use adopted a positive opinion recommending approval of the camizestrant combination on May 22, 2026. The drug is also approved in the United Arab Emirates and Saudi Arabia in this setting, and regulatory reviews are ongoing in Japan and several other countries, all based on SERENA-6 data. The FDA's final decision on the camizestrant FDA decision remains pending, with the outcome likely to hinge on whether the supplementary ctDNA analyses satisfy the agency's benefit-risk assessment in the context of the earlier advisory committee vote. *** This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: [https://allsci.com/news/](https://allsci.com/news/) --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/camizestrant-fda-approval-delays-decision-on)