Novartis’ STAMP Inhibitor Scemblix Receives Positive CHMP Opinion for CML with Superior Efficacy and Safety vs. Bosulif

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News on June 25, 2022 /BioValleyBIOON/ -- Novartis recently announced that the European MedicinesManagementThe Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive review opinion, recommending approval.New Targeted Anticancer Drug STAMP Inhibitor Scemblix (asciminib): For the treatment of Philadelphia chromosome-positive chronic myeloid leukemia patients who have previously received at least 2 tyrosine kinase inhibitors (TKI).LeukemiaAdult patients with chronic phase (Ph+CML-CP).

Now, the CHMP opinion will be submitted to the European Commission (EC) for review, which is expected to make a final decision within the next 2 months. If approved,Scemblix will be the first CML therapy in Europe to specifically target the ABL myristoyl pocket (STAMP inhibitor), representing a significant therapeutic advancement for patients who are intolerant and/or resistant to existing TKI therapies.

Scemblix is a kinase inhibitor., obtained in the United States in October 2021FDAAccelerated 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 and the first CML treatment drug to function by specifically targeting the BCR-ABL1 protein myristoyl pocket (STAMP). Currently available competitive drugs work by binding to the ATP-binding site of the BCR-ABL1 protein. Scemblix acts on another part of the kinase, the ABL myristoyl pocket (STAMP), locking BCR-ABL1 in an inactive conformation. Thus, Scemblix can help address TKI resistance in CML patients and overcome defective BCR-ABL1 gene mutations associated with the overproduction of leukemia cells.

It is estimated that more than 6,300 people in Europe will beDiagnosisFor chronic myeloid leukemia (CML). Although many patients will benefit from available TKI therapies, a significant portion of patients may be intolerant or develop resistance to these treatments. In an analysis of CML patients previously treated with two TKIs, approximately 55% reported intolerance to prior treatments;A pooled analysis of second-line patients showed that up to 70% of patients did not achieve a major molecular response (MMR) within 2 years of follow-up.。

The positive review opinion of the CHMP is based on the results of the pivotal Phase 3 ASCEMBL trial. The study was conducted in Ph+CML-CP patients who were resistant or intolerant to at least 2 TKIs. The data showed,At Week 24 of Treatment,Compared with Pfizer's targeted anticancer drug Bosulif (bosutinib, 500mg once daily), treatment with Scemblix (40mg twice daily) for 24 weeks nearly doubled the MMR (25.5% vs 13.2%; p=0.029 for both arms).. In addition,Compared with the Bosulif treatment group, the discontinuation rate due to adverse events in the Scemblix treatment group was reduced by more than three times (5.8% vs 21.1%).. These results were confirmed during long-term follow-up:At Week 96 of treatment, the MMR rate in the Scemblix group was more than twice that of the Bosulif group (37.6% vs 15.8%).These results continue to support the use of Scemblix in Ph+ CML-CP patients who have previously received at least two TKIs, and it has the potential to change the standard of clinical care through a differentiated mechanism of action.

Dr. Andreas Hochhaus, Director of Hematology and Medical Oncology at Jena University Hospital in Germany, stated: "Despite advancements in CML treatment over the past 20 years, many patients still experience side effects and drug resistance, impacting their...Quality of Life"And put them at risk of disease progression or even death. If approved, Scemblix's novel mechanism of action would offer another option to address these challenges faced by patients, bringing new hope for the management of their condition."

In recent years, progress has been made in the treatment of CML. Clinicians can choose from a few TKIs when treating patients with Ph+ CML, including Novartis' Gleevec (imatinib) and Tasigna (nilotinib). Most patients receiving drug therapy 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.Previously, the U.S. FDA granted asciminib Fast Track Designation (FTD). In February 2021, the FDA granted asciminib two Breakthrough Therapy Designations (BTD): (1) for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase (Ph+ CML-CP) who have previously received at least two tyrosine kinase inhibitors (TKIs); (2) for the treatment of adult patients with Ph+ CML-CP carrying the T315I mutation.

Currently, Novartis is conducting multiple clinical trials to evaluate Scemblix in CML patients who have received various therapies, as well as in combination with other TKIs for the treatment of newly diagnosed CML patients. (Bioon.com)

Source of Original Text:Novartis receives positive CHMP opinion for Scemblix, a novel treatment for adult patients with chronic myeloid leukemia