Novartis eyes filings for leukaemia drug asciminib after phase 3 win

A first-in-class STAMP inhibitor developed by Novartis – asciminib – has outperformed a current drug for chronic myeloid leukaemia (CML) in a head-to-head trial, setting up regulatory filings.

The ASCEMBL trial compared asciminib (ABL001) to Pfizer’s Bosulif (bosutinib) in Philadelphia chromosome-positive CML patients who had previously been treated with two or more tyrosine kinase inhibitors (TKIs), the go-to treatment for this form of CML.

Current treatment for these patients relies on first-generation TKI imatinib – sold by Novartis as Glivec but also available as a generic – as well as second-generation drugs such as Bosulif, Bristol-Myers Squibb’s Sprycel (dasatinib) and Novartis’ Tasigna (nilotinib).

These drugs have transformed the prospects of people with CML, but most patients eventually see their cancer progress despite TKI therapy, and resistance to these drugs can lead to treatment failures. They can also be hard to tolerate, as they can affect healthy as well as leukaemic cells.

Asciminib’s novel mechanism of blocking STAMP – the ABL myristoyl pocket of the BCR-ABL tyrosine kinase – could sidestep conventional TKI resistance and side effects and provide a new third-line treatment option for CML patients, says Novartis.

In ASCEMBL, asciminib was better than Bosulif at achieving a major molecular response (MMR) at 24 weeks than Bosulif in Ph+ CML patients in chronic phase, the stage of the disease when the blood and bone marrow contains less than 10% malignant cells.

Molecular response is measured using a genetic probe to detect BCR-ABL gene mutations in blood or bone marrow based on the number of leukaemic cells present, and is considered to be MMR when the mutations are found at a rate of 1/1000th or less than would be expected in an untreated patient.

“Our ability to treat patients with TKIs changed CML care forever. However, the risk of disease progression is a reality for many patients,” said Novartis’ chief medical officer John Tsai.

“These results with asciminib are a testament to our commitment to further transform CML care – this time through STAMP inhibition, by exploiting a natural regulatory mechanism of the ABL kinase,” he added.

The FDA has awarded the drug fast-track status, given to new therapies that treat a serious or life-threatening condition and fill an unmet medical need, which means it could be eligible for a speedy review after filing.

Novartis originally planned to go after approval as a second-line treatment option as well on the back of another trial called ASC4MORE, but is sticking with third-line for the time being.

Data from the ASCEMBL trial will be submitted for presentation at an upcoming medical meeting, and results will be shared with regulatory authorities, said the drugmaker.

If approved, asciminib would beef up Novartis' CML portfolio, which is a big earner for the company. Tasigna made sales of $1.8 billion last year, and despite generics Glivec is still a blockbuster brand for the company, adding almost $1.3 billion to its 2019 revenues.