Novartis receives approval for third-generation leukaemia therapy

Swiss company Novartis has led the charge in the treatment of chronic myeloid leukaemia (CML) for more than two decades since the launch of its first-generation tyrosine kinase inhibitor (TKI), Gleevec/Glivec (imatinib).

Now the US Food and Drug Administration (FDA) has granted Novartis’ third-generation CML therapy Scemblix (asciminib) accelerated approval for adult patients in two distinct indications.

The first is for patients with Philadelphia chromosome-positive CML in chronic phase (Ph+ CML-CP) who have been previously treated with two or more tyrosine kinase inhibitors (TKIs).

This indication was supported by data from the pivotal phase 3 ASCEMBL trial, where Scemblix demonstrated significant and clinically meaningful superiority over Pfizer’s second-generation treatment Bosulif (bosutinib).

The second indication is in patients with CML who also have the T315I mutation, supported by additional data from a phase 1 trial.

“The introduction of TKIs twenty years ago revolutionised treatment for CML; however, there remain many patients who do not respond adequately to at least two available treatments and often experience challenging side effects that add a burden to their daily lives,” said Lee Greenberger, Chief Scientific Officer at The Leukemia & Lymphoma Society. “The approval of Scemblix may offer hope to patients by addressing gaps in CML care.”

The ASCEMBL trial saw a much lower discontinuation rate due to side effects.

“CML can be difficult to treat when currently available treatments fail patients, when treatment side effects cannot be tolerated, or sometimes both,” said Dr Michael J. Mauro, haematologist at Memorial Sloan Kettering Cancer Center in New York. “The addition of Scemblix to the CML treatment landscape gives us a novel approach to combat this blood cancer, helping address clinical challenges in patients struggling after switching to a second treatment, as well as in patients who develop the T315I mutation and face significantly worse outcomes.”

The accelerated approval for Scemblix is based on major molecular response (MMR) rate data so continued approval for the therapy will be contingent on proof of its clinical benefit which has to be collected over time.

Scemblix has a novel mechanism of action known as a STAMP inhibitor, which it is hoped may address the problem of resistance in patients with CML and overcome mutations as a defective gene associated with over-production of leukaemic cells.

Novartis has initiated regulatory filings for Scemblix in multiple countries and regions across the globe.