Kaken details the data behind its PI3K inhibitor filing

Kaken Pharmaceutical has revealed the phase 3 results that supported its recent marketing application for serabelisib in Japan, vying to become the next PI3K alpha inhibitor to reach the market.

Serabelisib (KP-001) was filed with Japan's regulatory authority in May as a therapy for the treatment of vascular malformations, a catch-all term for a group of diseases characterised by abnormal, tangled clusters of veins, arteries, capillaries, or lymph vessels that generally develop before birth.

The drug was originally developed by Intellikine, which was acquired by Takeda in 2011, and Kaken acquired rights to the drug in December 2021 via a $78 million buyout of ARTham Therapeutics, a Takeda spinout.

Vascular malformations are a new indication for the PI3K alpha inhibitor class, which currently features two breast cancer therapies, namely Novartis' Piqray (alpelisib) and Roche's Itovebi (inavolisib), with a host of others for breast cancer coming through the industry pipeline.

Outside Japan, serabelisib is being developed by Faeth Therapeutics, which is developing it as part of a PI3K/AKT/mTOR-acting cocktail, in combination with mTORC1/2 inhibitor sapanisertib, for endometrial and breast cancer with confirmed PI3K/AKT/mTOR pathway mutations.

It has been granted orphan status for the vascular malformations indication in Japan, on the back of preliminary clinical trial results from an open-label phase 3 trial that showed a significant improvement in the primary endpoint, which was the proportion of patients showing a 20% or greater reduction in lesion volume measured using MRI at 24 weeks.

Newly-released data from a longer-term confirmatory trial, presented at a meeting of the Japanese Society for the Study of Vascular Anomalies last week, revealed that outcome was achieved in 30.6% of subjects, which was well above the 6.7% threshold calculated to demonstrate efficacy.

Liver function test abnormalities were identified as a potential risk associated with serabelisib, but were reversible and could be managed through laboratory monitoring during treatment, according to Kaken.

The trial involved 36 patients with venous malformations, lymphatic malformations, and Klippel-Trenaunay syndrome (KTS), a rare congenital condition characterised by port-wine stains, varicose veins, and overgrowth of soft tissue and bone, usually affecting only one limb.

Serabelisib is thought to work in vascular malformations by inhibiting the growth of new blood vessels (angiogenesis).