Roche’s bid to build a better Piqray yields phase 3 breast cancer win, opening door to regulators

Roche’s pitch to reset the standard of care in a breast cancer population has cleared a late-phase hurdle. The drugmaker’s attempt to improve on Novartis’ Piqray and deliver a first-line PI3K inhibitor has yielded an improved progression-free survival (PFS) in phase 3, teeing up talks with regulatory authorities. 

The investigational drug, inavolisib, hits the same target as Piqray. What differentiates the molecule, in Roche’s view, is significantly better potency and selectivity against other PI3K isoforms. The result is a drug candidate that Roche thinks can provide prolonged inhibition of the PI3 pathway, driving improved efficacy, while also being more tolerable than Piqray, which is limited to second line and later use.

Roche put its theory to the test in a phase 3 clinical trial in patients with PIK3CA-mutant, hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer. Investigators randomized the 325 patients to receive inavolisib or placebo on top of palbociclib and fulvestrant, drugs respectively sold as Ibrance by Pfizer and Faslodex by AstraZeneca.

Adding inavolisib to the other two drugs significantly increased PFS, causing the study to hit its primary endpoint. The overall survival data were immature at the time of the analysis, but Roche saw a “clear positive trend” and is continuing to track participants. Roche is yet to share any efficacy numbers but it painted a positive picture of readout that it identified as a key event in the run up to the data drop.

“If that study is positive, we think it will become standard of care because, ultimately, the best chance to really change the natural history of HR-positive breast cancer is to do it right the first time,” Charles Fuchs, SVP, global head of oncology and hematology product development, at Roche, said at an investor event in September.

The information on safety and tolerability is similarly scant, with Roche only saying the combination was well tolerated, adverse events were in line with the known safety profiles of the three molecules and no new safety signals were seen. A focus on making a more tolerable PI3K inhibitor enabled Roche to combine inavolisib with full doses of Ibrance and Faslodex 

Roche, which plans to share the results with health authorities, will provide a proper look at the data at an upcoming medical meeting. In parallel, the Big Pharma will continue to study inavolisib in two other phase 3 trials that are pitting the candidate against Piqray in second-line patients and in combination with Roche’s breast cancer cocktail Phesgo.