Novartis' STAMP Inhibitor Asciminib Demonstrates Superior Efficacy Over Pfizer's Bosulif in Phase III CML Trial

August 27, 2020 /Bio ValleyBIOON/ --Novartis(Novartis) recently announced the evaluation of the targeted anticancer drug asciminib (ABL001) for the treatment of chronic myeloidLeukemiaThe Phase III ASCEMBL study in chronic myeloid leukemia (CML) met its primary endpoint at the primary analysis.

ASCEMBL is a multicenter, open-label, randomized Phase III study conducted in 234 patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) who had previously received two or more ATP-binding site tyrosine kinase inhibitors (TKIs; e.g., imatinib, nilotinib, dasatinib, radotinib, ponatinib), comparing asciminib with Bosulif (bosutinib,Pfizerthe efficacy and safety of the company's products).

Patients enrolled in the study had experienced failure of their most recent tyrosine kinase inhibitor (TKI) therapy (meeting the definition of treatment failure per the 2013 ELN guidelines) or intolerance (defined as a BCR-ABL1 ratio >0.1% on the International Scale [IS] at screening). In the study, patients were randomized to receive once-daily oral asciminib or Bosulif. The primary endpoint was the major molecular response (MMR) rate at Week 24 of treatment.

The results showed that the study met its primary endpoint in the primary analysis. The data demonstrated that asciminib had a significant advantage over Bosulif in terms of major molecular response rate (MMR). The findings of this study will be submitted to the upcoming medical conference.Conference, and will be shared with regulatory authorities.

NovartisJohn Tsai, M.D., Global Drug Development Head and Chief Medical Officer, stated: “Our ability to treat patients with TKIs has forever changed the care of CML. However, for many patients, the risk of disease progression is a reality, particularly those who develop resistance to sequential TKI therapies or those who cannot adhere to treatment due to intolerable side effects. We are deeply grateful to the patients and researchers worldwide who participated in this study. These results related to asciminib demonstrate our commitment to further transforming the treatment of CML, this time through STAMP inhibition, leveraging a natural regulatory mechanism of the ABL kinase.”

Chemical Structure of Asciminib (Image Source: medchemexpress.cn)

In recent years, progress has been made in the treatment of CML, and clinicians have a selection of a few TKIs to choose from when treating patients with Ph+ CML, includingNovartisGleevec (imatinib) and Tasigna (nilotinib). Most patients receiving drug therapy remain alive after 10 years, but there is still a risk of disease progression.

Although patients who develop resistance to initial therapy can switch to another TKI (i.e., sequential TKI therapy), many approved therapeutic agents target the same ATP-binding site on the ABL1 kinase. The similarity among these therapies means that a mutation in one region of this kinase can render many drugs ineffective. In other words, sequential TKI therapy may be associated with increased resistance and intolerance.

Asciminib is a STAMP inhibitor that has previously been approved in the United StatesFDAGranted Fast Track Designation (FTD). This is an investigational drug that specifically targets the myristoyl pocket of the BCR-ABL1 protein (STAMP), locking BCR-ABL1 in an inactive conformation.

Currently marketed competitive drugs work by binding to the ATP-binding site of the BCR-ABL1 protein. In contrast, asciminib exerts its effect by targeting another region of this kinase, namely the ABL myristoyl pocket. As a STAMP inhibitor, asciminib has the potential to address TKI resistance and intolerance in the later stages of CML treatment, thereby improving patient prognosis.

Currently,NovartisMultiple initiatives are underwayClinical Trial, to evaluate asciminib in patients with CML who have received multiple prior therapies, as well as in combination with other TKIs for the treatment of newDiagnosisof CML patients. (Bioon.com)

Original Source: Novartis' Asciminib Bests Pfizer's Bosulif in Phase 3 Leukemia Trial