Novartis Announces New Long-Term Data for STAMP Inhibitor Scemblix in CML, Showing Sustained Superior Efficacy and Safety vs. Pfizer’s Bosulif

December 12, 2021 /BioValleyBIOON/ --Novartis(Novartis) recently presented new 48-week data from the Phase 3 ASCEMBL trial of the novel targeted anticancer drug Scemblix (asciminib, ABL001) at the 63rd American Society of Hematology Annual Meeting (ASH2021) in 2021. The results showed that, in adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase (Ph+ CML-CP) who had previously received at least two tyrosine kinase inhibitors (TKIs),Scemblix withPfizerCompared with the targeted anticancer drug Bosulif (bosutinib), the efficacy and safety superiority at the time of the primary analysis (24 weeks) was maintained during the long-term follow-up (48 weeks).。

Scemblix is a kinase inhibitor that was approved by the United States in October 2021.FDAAccelerated approval for the treatment of adult patients with Ph+ CML-CP who have previously received at least 2 TKI treatments.Scemblix is a STAMP inhibitor, the first CML treatment drug to work by specifically targeting the BCR-ABL1 protein myristoyl pocket (STAMP).。The currently marketed competitive drugs work by binding to the ATP-binding site of the BCR-ABL1 protein.

Scemblix acts by targeting another part of the kinase, the ABL myristoyl pocket (STAMP), locking BCR-ABL1 into an inactive conformation. Thus, Scemblix helps address TKI resistance in CML patients and overcomes defective BCR-ABL1 gene mutations associated with the overproduction of leukemia cells.

Chemical Structure of Asciminib (Source: medchemexpress.cn)

Announced at the ASH meeting48-week data show that the Scemblix treatment group had more than double the MMR compared to the Bosulif treatment group (29.3% vs 13.2%), with a discontinuation rate due to adverse events more than three times lower (7.1% vs 25%).The previously published 24-week data showed that the MMR rate in the Scemblix treatment group was nearly double that of the Bosulif treatment group (25.5% vs 13.2%; p=0.029), and the discontinuation rate due to adverse events was more than three times lower (7% vs 25%).

In the latest analysis presented at the meeting, responses were also shown to be durable, with 60 of 62 patients in the Scemblix treatment group maintaining MMR at the last assessment. Scemblix continued to provide favorable deeper molecular responses (MR) through MR4 and MR4.5, with MR4 and MR4.5 rates at week 48 being 10.8% and 7.6%, respectively, compared to 3.9% and 1.3% in the Bosulif group. Additionally, during the 48-week period, the cumulative proportion of patients achieving BCR-ABL1[IS] ≤1% was higher in the Scemblix treatment group than in the Bosulif treatment group (50.8% vs. 33.7%). BCR-ABL1[IS] ≤1% is a predictor of better long-term outcomes in this heavily pretreated patient population.

Memorial Sloan Kettering Cancer Center (MSK) Hematologist and MyeloproliferativeTumorProject leader Michael J. Mauro, M.D., commented: "We often see that the sequential use of TKI drugs may lead to an increased failure rate, and as patients progress to later lines of therapy, there is greater concern about potential treatment-related side effects."Scemblix Offers an Increasingly Mature Option for CML Patients Who Have Tried Two or More TKIs, and the Drug Takes a Different Approach to Provide Targeted Inhibition for Better Management of CML。”

Week 24 Results from the Phase 3 ASCEMBL Study (Image Source: Scemblix Prescribing Information)

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

Although patients who develop resistance to initial treatment can switch to another TKI (i.e., sequential TKI therapy), many approved treatments target the same ATP-binding site on the ABL1 kinase. The similarity between these therapies means that a mutation in one region of the kinase can render many drugs ineffective. That is to say,Sequential TKI therapy may be associated with increased resistance and intolerance.

As a STAMP inhibitor, Scemblix can overcome mutations at the ATP-binding site of BCR-ABL1, which may help address TKI resistance in later-stage CML treatment and potentially resolve off-target activity, thereby improving patient outcomes. Additionally, the U.S. FDA has granted asciminib Fast Track Designation (FTD). In February 2021,FDAAsciminib Granted 2 Breakthrough Therapy Designations (BTD): (1) For the treatment of adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) who have previously received at least 2 tyrosine kinase inhibitors (TKIs); (2) For the treatment of adult patients with Ph+ CML-CP carrying the T315I mutation.

Currently, Novartis is conducting multipleClinical Trial, evaluating Scemblix for CML patients who have received multiple therapies, as well as in combination with other TKIs for the treatment of newDiagnosisCML patients. In the third quarter earnings callMeetingAbove,NovartisIt was disclosed that a Scemblix first-line treatment study has been initiated. (Bioon.com)

Source of the original text:Novartis Scemblix® demonstrates sustained response rate in 48-week follow-up in patients with chronic myeloid leukemia