Novel CML-treatment asciminib performs as hoped in phase III trial

September 2020 Pharma News Willem van Altena
CHRONIC MYLELOGENOUS LEUKEMIA (also called MYELOGENOUS LEUKEMIA), many MYELOBLASTS (Immature white blood cells or leukocytes), 250X. This is a human blood smear showing numerous Myeloblasts (immature white blood cells or leukocytes). It also shows an Eosinophil with reddish granules and a bilobed nucleus, and a BAND CELL (near the center, has a horseshoe-shaped nucleus) that develops into a NEUTROPHIL (the most common white blood cell). Large numbers of these is considered abnormal. These cells originate in the red bone marrow (MYELOID tissue), hence the name Myelogenous. Leukemia is a cancer of the blood forming tissues, and involves an abnormal proliferation of white blood, cells (leukocytes), many of which are immature, and do not perform normal functions. This great increase in leukocytes can also crowd out red blood cells and platelets. This image also shows numerous, smaller red blood cells (erythrocytes).

The medicine asciminib is showing promising results in the treatment of patients with chronic myeloid leukaemia (CML). Recently, Swiss pharma company Novartis presented results from a phase III trial which compares asciminib with bosutinib, a drug that is currently often used to treat CML patients. The trial focused on CML patients who had undergone two or more prior treatments with tyrosine kinase inhibitors (TKI).

Asciminib is an allosteric inibitor that specifically targets the ABL myristoyl pocket (STAMP). As a STAMP inhibitor, asciminib may help address tyrosine-kinase inhibitor (TKI)-resistance and intolerance in later treatment lines of CML, and it is being studied in several clinical trials in hopes of helping patients across multiple treatment lines of CML. Asciminib inhibits both the normal as mutted BCR-ABL1 protein, including the T315I mutation. Thus far the safety of asciminib in the treatment of Philadelphia chromosome positive CML (Ph+ CML) had not been investigated.

In the ASCEMBL phase III study, asciminib was shown after 24 weeks to have a better molecular response compared to bosutinib in patients with Ph+ CML, who had undergone two or more previous treatments with TKI. Consequently, Novartis has announced to submit asciminib to the EMA in order to obtain admission to the European markt. Meanwhile, the FDA in the USA has already stated that asciminib is eligible for a fast-track admission procedure.

Further reading
Read the full press release from Novartis