Genentech: FDA accepts NDA for giredestrant after positive Phase III adjuvant results in early ER‑positive breast cancer

Regulatory status

The FDA has accepted Genentech’s NDA for oral SERD giredestrant as adjuvant therapy for ER‑positive, HER2‑negative stage I–III breast cancer under Priority Review, with a PDUFA date of November 30, 2026; an NDA for giredestrant plus everolimus in ESR1‑mutated advanced ER‑positive disease has also been accepted with an FDA decision expected December 2026.

Key Phase III results

lidERA (n>4,100) showed adjuvant giredestrant reduced the risk of invasive disease recurrence or death by 30% versus standard‑of‑care endocrine therapy (iDFS HR=0.70; 95% CI 0.57–0.87; p=0.0014); three‑year iDFS was 92.4% versus 89.6%; overall survival data are immature but trending positive; adverse events were manageable and discontinuation was 5.3% versus 8.2% with standard therapy; additional analyses were presented at ASCO 2026.

Mechanism and development program

Giredestrant is an oral next‑generation selective estrogen receptor degrader that blocks estrogen binding and triggers receptor degradation; the clinical program includes five company‑sponsored Phase III trials across settings, notably lidERA (adjuvant), evERA (with everolimus in locally advanced/metastatic), persevERA (with palbociclib in endocrine‑sensitive recurrent disease), pionERA (with CDK4/6 in adjuvant‑resistant advanced disease) and heredERA (with dual HER2 blockade in ER+/HER2+ disease).

Unmet need

Globally there are ~2.3 million breast cancer diagnoses annually; about 70% are ER‑positive and most are detected at early stage, yet up to one‑third of patients eventually recur after adjuvant endocrine therapy and many stop or interrupt treatment due to tolerability, highlighting the need for more effective, better‑tolerated adjuvant options.