Novartis snaps up PI3Kα breast cancer drug in $3bn deal

Novartis has reached an agreement to buy a PI3K-targeting drug for breast cancer from Synnovation Therapeutics, paying a hefty $2 billion upfront for the asset, which is in phase 1/2 testing.

The deal, which includes another $1 billion potential milestone payments, will see Novartis acquire Synnovation's subsidiary company Pikavation Therapeutics, which was set up to spearhead the development of a portfolio of pan-mutant selective PI3Kα inhibitors.

Novartis already sells one PI3Kα inhibitor, Piqray/Vijoice (alpelisib), which has been cleared since 2019 as a second-line therapy for patients with advanced HR-positive, HER2-negative breast cancer with a PIK3CA mutation, following progression on or after endocrine therapy.

However, Piqray is coming under pressure from Roche's rival PI3Kα-targeting drug Itovebi (inavolisib), which last year became the first drug in the class to move into the first-line treatment setting and show a survival benefit.

Both Piqray and Itovebi have toxicity warnings on their labels for side effects like high blood sugar, diarrhoea, and nausea/vomiting, and drug developers are now developing drugs that selectively target mutant forms of PI3K and spare wild-type forms, seeking to preserve efficacy in breast cancer and offer a cleaner safety profile.

SNV4818 is one such candidate coming through the industry pipeline, and is currently being evaluated in a phase 1/2 study involving patients with PIK3CA-mutated breast cancer and other advanced solid tumours, both alone and in combination with fulvestrant and palbociclib, with results due in 2027.

Other mutant PI3Kα inhibitors in clinical testing include Eli Lilly's tersolisib (formerly STX-478), acquired when it bought Scorpion Therapeutics last year, as well as Relay Therapeutics' zovegalisib, OnKure's OKI-219, and Sensei BioTherapeutics' dual PI3Kα and mTORC1/2 inhibitor combination Piktor (serabelisib and sapanisertib), which came from its takeover of Faeth Therapeutics in February.

"While mutated PI3Kα is a well‑established driver in HR+/HER2‑ breast cancer, there remains a challenge in achieving effective pathway inhibition with a tolerable therapeutic profile," said Shreeram Aradhye, Novartis' head of development.

"SNV4818 applies new mutant‑selective chemistry to more precisely target tumour biology while sparing normal cells," he added. "This approach has the potential to translate proven biology into improved tolerability and more durable benefit for patients through precision medicine."

Novartis said the drug "its naturally alongside CDK inhibitors as well as endocrine […] therapies as part of a potential combination regimen," alluding to its potential to complement with other drugs in its portfolio like fast-growing CDK4/6 inhibitor Kisqali (ribociclib).

It expects the acquisition to close in the first half of this year.