Kite Pharma Inc. has staked a claim to be the first to file a chimeric antigen receptor T cell (CAR-T) therapy in the EU, having submitted a marketing authorization application for axicabtagene ciloleucel (KTE-C19) ahead of Novartis AG's leading product CTL019 (tisagenlecleucel).
The submission, based on the ZUMA-1 trial (see sidebar), is for its use as a treatment for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL) and primary mediastinal B-cell lymphoma (PMBCL) who are ineligible for autologous stem cell transplant.
The application will beat a relatively quick path to EU approval based on its inclusion in the European Medicines Agency's (EMA's) newly established Priority Medicines (PRIME) regulatory initiative for patients with refractory DLBCL. PRIME aims to support the development and accelerate the review of new therapies to treat patients with a high unmet need. Axicabtagene ciloleucel is already under review by the US FDA, with a Nov. 29 PDUFA action date.
The application should be buoyed by the positive sentiment surrounding this innovative field following the smooth sailing Novartis's CTL019 recently enjoyed at its FDA advisory committee meeting on July 12. The panel unanimously voted in favor of its approval for pediatric relapsed/refractory B-cell acute lymphoblastic leukemia (ALL). (Also see "CAR-T Companies Hang Onto Novartis' Coat-Tails After Historic FDA Panel Vote" - Scrip, 13 Jul, 2017.)
However, some said the positive assessment was likely aided by the high level of unmet need in pediatric ALL, and that the risk/benefit analysis may be trickier to dissect for other therapies in different indications. The Kite product did face bumps in development when one very ill NHL patient died from cerebral edema in the extension phase of ZUMA-1 – the same severe side effect that derailed another competitor in the field, Juno Therapeutics Inc.'s JCAR015. Nevertheless, analysts also are confident of success for Kite's product. (Also see "Novartis CAR-T AdComm Was Smooth Sailing, But Will That Be An Anomaly?" - Scrip, 14 Jul, 2017.)
Novartis also is developing CTL019 in DLBCL and recently reported early results for it in this indication from the JULIET study that appear to be comparable with Kite's offering. (Also see "Much Anticipated JULIET Data Show Novartis Playing Catch-Up On CAR-T Manufacturing" - Scrip, 7 Jun, 2017.)
NHL is a type of blood cancer that affects around 93,000 people in Europe each year. DLBCL is one of the subtypes of NHL that is aggressive or fast-growing. Kite estimates that approximately 7,800 patients in the five largest EU markets may qualify for treatment with its CAR-T therapy.