Roche bounces back in PIK3 with inavolisib data

A few years ago, Roche abandoned the development of its lead PIK3CA-targeting drug taselisib on safety grounds, allowing rival Novartis to beat it to market, but now it has the programme back on track.

A phase 3 readout for follow-up drug inavolisib as a combination therapy with Pfizer’s CDK4/6 inhibitor Ibrance (palbociclib) and fulvestrant has shown the drug to be more effective at preventing disease progression or death than Ibrance/fulvestrant alone when used as first-line treatment for a specific group of patients with PIK3CA-mutated advanced or metastatic breast cancer.

There was also a trend towards improved survival with the triplet therapy in the patients, whose tumours were also hormone-positive, HER2-negative, and endocrine therapy-resistant.

PIK3CA mutations are found in approximately 40% of HR-positive breast cancers and are linked to faster tumour growth, disease progression, and treatment resistance, so, the potential patient population that could be targeted by inavolisib if approved is pretty large.

So far, Novartis’ Piqray (alpelisib) is the only PIK3CA inhibitor to have reached the market for breast cancer, having been cleared in 2019 as a second-line therapy alongside fulvestrant for patients with PIK3cA-positive, HR-positive, and HER2-negative advanced breast cancer that has progressed on or after endocrine-based therapy. It made $428 million in sales in the first nine months of this year.

Other drugs in the class - including Gilead Sciences’ Zydelig (idelalisib), Bayer’s Aliqopa (copanlisib), and Verastem’s Copiktra (duvelisib) - have been approved for blood cancers like leukaemia and lymphoma, but carry warnings on their labels of serious side effects and haven’t been able to make the switch to solid tumour therapy.

Roche’s chief medical officer, Levi Garraway, said the data could be a “transformative medical advance” for patients with this type of breast cancer, adding: “We look forward to expanding our portfolio of breast cancer medicines into the HR-positive space and bringing this potentially best-in-class new treatment option to patients as quickly as possible.”

Roche thinks the data from the phase 3 INAVO120 could be enough to support regulatory filings for the drug, which it says promises to have an improved safety profile to other drugs in the class.

It is currently running two other phase 3 studies of inavolisib, including a head-to-head comparison to Piqray – both in combination with fulvestrant – in HR-positive HER2-negative breast cancer patients previously treated with CDK4/6 inhibitor and endocrine combination therapy (INAVO121).

The third trial (INAVO122) is comparing the combination of inavolisib with Roche’s HER2-targeting drug Phesgo (pertuzumab plus trastuzumab) to Phesgo alone as maintenance therapy after first-line therapy for HER2-positive breast cancer patients.