Weeks after Sanofi flop, Roche's rival breast cancer drug flunks phase 2 test

Chalk up another setback to oral selective estrogen receptor degraders (SERDs). In the wake of data that sank Radius Health’s stock and the failure of Sanofi’s prospect, Roche has revealed giredestrant missed the mark in a midphase breast cancer trial, raising doubts about the drug ahead of further data drops.

The Swiss Big Pharma disclosed the failure of giredestrant in its first-quarter results. The study randomized 303 patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer to receive giredestrant or the physician's choice of AstraZeneca’s Faslodex or an aromatase inhibitor as a second- or third-line treatment. Participants in the giredestrant cohort took the oral SERD once a day in each 28-day cycle.

Giredestrant failed to beat the progression-free survival achieved by the physician’s choice of endocrine monotherapy, causing the study to miss its primary endpoint. Even so, Roche took some positives away from the trial, noting that “efficacy data were encouraging with a more pronounced benefit in patients with higher dependence on estrogen receptor activity.” The overall survival data are still immature, the company added.

Roche is trailing Radius’ elacestrant in the race to bring an oral SERD to market, although, while the front runner hit the mark in a pivotal trial in October, a deeper dive into the data in December caused its stock to tank. Sanofi’s amcenestrant is also in the running but failed a pivotal trial last month. Like Roche, Sanofi pitted its oral SERD against the physician’s choice of a range of drugs, including Faslodex, as a second-line or later treatment of ER+/HER2- advanced or metastatic breast cancer.

All of the companies are pursuing the idea that there is a blockbuster niche awaiting oral breast cancer drugs that target a subpopulation of patients whose cancer is driven by estrogen receptor signaling. The blockbuster hopes have built up despite the moderate commercial sales of AstraZeneca’s injectable SERD Faslodex and the failures of earlier oral candidates, including the prospects Roche acquired in its $725 million takeover of Seragon Pharmaceuticals.

While Roche took the positives from the giredestrant trial, the failure against the primary endpoint is still a blow to a candidate that forms part of a late-phase pipeline focused on 10 new molecular entities. Giredestrant is in a pair of phase 3 trials that are testing the drug in two other settings, namely in combination with Pfizer’s Ibrance as a first-line treatment for metastatic breast cancer and as an adjuvant in early breast cancer.

Coming weeks after a long shot on anti-TIGIT drug tiragolumab failed, the giredestrant flop continues a bad start for Roche’s pipeline in 2022. Going into the year, the company included the giredestrant study alongside four trials of tiragolumab and a study of gantenerumab in Alzheimer’s disease on a short list of notable upcoming investigational drug data drops. Now, having gone 0 for 2 so far, Roche is left looking to three trials of tiragolumab and the study of gantenerumab to salvage its late-phase pipeline.