Roche's Experimental Breast Cancer Drug Giredestrant Fails Phase 3 Trial

Roche's giredestrant plus palbociclib missed its primary endpoint in a phase 3 breast cancer trial. Numerical improvement was seen without statistical significance. Shares fell sharply; a second readout is due in 2027.

Roche said Monday that its experimental breast cancer drug giredestrant, in combination with Pfizer's Ibrance (palbociclib), failed to meet the primary objective of a statistically significant improvement in progression-free survival in a phase 3 clinical trial in patients with advanced breast cancer. The persevERA Breast Cancer study included patients with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer.

The study did not achieve a statistically significant improvement in progression-free survival versus letrozole plus palbociclib, although a numerical improvement was observed. The drug combination was well tolerated, with adverse events consistent with the known safety profiles of each treatment, Roche said.

This was the first of two late-stage studies evaluating giredestrant as a first-line treatment. Results from the second study, pionERA, which is evaluating giredestrant combined with a CDK4/6 inhibitor in endocrine-resistant ER-positive, HER2-negative breast cancer, are expected to be published in 2027.

Earlier trials had shown promise for giredestrant. The evERA study was the first positive phase 3 readout for the drug, and lidERA showed benefit in the early-stage setting, with the drug cutting the risk of tumour recurrence in breast cancer patients who had previously been treated. Giredestrant also succeeded as an add-on, or adjuvant, treatment in patients with a form of early-stage breast cancer.

Roche said it sees a path forward for combining giredestrant with a CDK4/6 inhibitor in the adjuvant setting, and is conducting further studies. The company's chief medical officer and head of global product development said the efficacy demonstrated in evERA and lidERA provides clear validation of the clinical activity of giredestrant and reinforces the strength of the company's expanding clinical development programme.

Roche applied for U.S. Food and Drug Administration approval of giredestrant based on evERA data, and the FDA has set a Prescription Drug User Fee Act date of 18 December. Giredestrant belongs to a drug class known as oral selective oestrogen receptor degraders (SERD), used to fight tumours that grow in response to oestrogen, which account for up to 80% of all breast cancer cases.

Roche's shares fell more than 7% at one stage on Monday, their biggest decline in nearly a year, before trading down 4.1% at 327.20 Swiss francs by 1335 GMT.

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