Dive Brief:

• Roche’s experimental drug giredestrant missed the main goal of a Phase 3 trial testing it as an initial treatment for breast cancer, the company said Monday. A combination of the therapy and Pfizer’s Ibrance failed to delay progression or death compared to Ibrance and hormone treatment.
• The data is a blow to the Swiss drugmaker’s ambitions for giredestrant, which is already under Food and Drug Administration review in people whose breast cancer has progressed and succeeded in staving off relapses after surgery.
• The trial’s failure will also likely reinforce doubts about the commercial potential of drugs in giredestrant’s class, called oral SERDs. The two approved drugs in the class, Menarini’s Orserdu and Eli Lilly’s Inluriyo, have so far only been approved for people whose breast cancer carries a certain mutation.

Dive Insight:

Roche shares fell 3% in trading Monday on the Swiss exchange, following a previous drop on Friday due to disappointing data from an obesity drug.

Roche has vocalized aspirations that giredestrant might become a new treatment standard for people whose breast cancer is sensitive to hormone treatment but is negative for a protein called HER2. It hasn’t given up on that hope, as Roche's medical chief, Levi Garraway, said in a statement that the company remains “confident in the potential” of giredestrant in early and advanced disease.

If the trial, called persevERA, had succeeded, giredestrant would have been the first oral SERD to help delay disease progression or death in first-line breast cancer when compared to standard of care. Inluriyo and Orserdu are available for use in people whose disease has advanced after initial treatment, but neither Lilly nor Menarini have run a Phase 3 trial in the frontline setting.

Jefferies analyst Michael Leuchten wrote in a note to clients Monday that the data “pulls the rug from under giredestrant,” calling into question whether the drug can become a multibillion-dollar seller. In addition to Monday’s setback, other questions hanging over giredestrant include the fact that its trial in the post-surgical care setting didin’t include the “CDK4/6 inhibitors” in Ibrance’s class.

Leuchten also wrote that Roche probably didn’t enroll enough people in the trial to be able to show a statistically significant benefit.

In addition to competing with Lilly and Menarini for market share, Roche is likely to face competition from another oral SERD, AstraZeneca’s camizestrant. The drug succeeded in a first-line trial with CDK4/6 inhibitors in part because it focused on those with the ESR1 mutation, for which Orserdu and Inluriyo also target. Camizestrant is also under review by the FDA, with an advisory committee meeting scheduled for April 30.

Leuchten also believes camizestrant’s trial in the adjuvant setting, which is due to report results next year, may be more relevant to clinical practice because it allows the use of CDK4/6 inhibitors and enrolled more patients, enabling it to potentially show a larger benefit.