Novartis’ Chronic Myeloid Leukemia Drug Demonstrates Superior Results to Pfizer’s

On December 8th, during the 62nd American Society of Hematology Annual Meeting & Exposition (ASH), Novartis presented the results from the Phase 3 clinical trial ASCEMBL, which evaluated the efficacy of Asciminib (ABL001) for the treatment of chronic myeloid leukemia. Asciminib nearly doubled the major molecular response rate and was associated with fewer adverse events than Bosulif (bosutinib).

Chronic myeloid leukemia (CML) is a type of bone marrow cancer characterized by an increase in the number of white blood cells in the blood. CML is caused when the chromosome 9 and 22 switch parts with each other. As a result, new fusion genes are created. In the case of the aberrant chromosome 22, also known as the Philadelphia chromosome, it creates a fusion protein known as BCR-ABL, promoting white blood cells to grow uncontrollably.

In 2020, approximately 8,450 people will be diagnosed with CML, and over 1,000 people will succumb to the disease. Current treatments include bone marrow transplants, chemotherapy, and drugs that block the protein produced by the BCR-ABL gene, such as Gleevec, Sprycel, Bosulif, and a couple of others. Most of these drugs inhibit the same region of the tyrosine kinase, the protein coded by the part of the BCR-ABL gene. With time, mutations can develop in this region, known as the ATP-binding site, resulting in resistance. Furthermore, these therapies have off-target effects since the ATP-binding site is very similar in many proteins. As a result, patients treated with two or more of these medicines experience intolerance due to adverse events, which results in dose interruptions and/or adjustments. New treatments targeting other regions of the tyrosine kinase could provide a valuable alternative for patients.

ASCEMBL Trial

Asciminib was developed to inhibit the tyrosine kinase protein; however, it inhibits the protein by binding a region known as the ABL myristoyl pocket (STAMP). The efficacy of Asciminib versus Bosulif in patients with Philadelphia chromosome-positive chronic myeloid leukemia was tested in the multicenter, open-label, randomized Phase 3 clinical trial known as ASCEMBL. After 24 weeks of treatment, more patients achieved complete cytogenetic response (CCyR), defined as no cells with the Philadelphia chromosome, are found in a sample of the bone marrow, with Asciminib treatment (40.8%) than patients taking Bosulif (24.2%). Additionally, treatment with Asciminib was twice as effective in achieving major molecular response, defined as a reduction in the BRC-ABL gene in the blood compared to Bosulif (25.5% versus 13.2%).

It is important to note that patients treated with Asciminib were less likely to discontinue treatment or required dose interruption and/or adjustment due to adverse events than patients in the Bosulif group. Together, these results postulate Asciminib as a viable alternative for the treatment for patients with CML.

“Novartis has been at the forefront of CML research for years – significantly changing the prognosis for patients. We are very proud to once again advance a potentially transformative medicine, a novel STAMP inhibitor, for those who do not adequately respond or are intolerant to currently available TKIs,” said John Tsai, Head Global Drug Development and Chief Medical Officer, Novartis. “There is a clear need in later lines of therapy, and based on these results, we believe Asciminib may become an important new development for patients. We look forward to sharing the data with regulatory authorities and moving forward with submissions worldwide.”

By Daniel Ojeda, Ph.D.

Related Article: ASH2020: VelosBio’s ROR1 Targeted Therapy Shines in Safety Trial

References

1. https://www.novartis.com/news/media-releases/novartis-investigational-stamp-inhibitor-asciminib-abl001-shows-superior-mmr-rate-bosulif-chronic-myeloid-leukemia-trial
2. https://www.cancer.org/cancer/chronic-myeloid-leukemia/treating/is-treatment-working.html#:~:text=A%20complete%20cytogenetic%20response%20(CCyR,still%20have%20the%20Philadelphia%20chromosome.
3. https://www.mayoclinic.org/diseases-conditions/chronic-myelogenous-leukemia/symptoms-causes/syc-20352417
4. https://ashpublications.org/blood/article/136/Supplement%201/34/473625/Structural-and-Biochemical-Studies-Confirming-the

Author

Daniel Ojeda