SCEMBLIX is a kinase inhibitor indicated for the treatment of adult patients with…Ph+ CML in CP with the T315I mutation.

Asciminib is a treatment option for CP-CML patients with the T315I mutation and/or CP-CML with resistance or intolerance to at least two prior TKIs.

Novartis today announced that the US Food and Drug Administration (FDA) accepted and granted Priority Review to the company’s New Drug Application (NDA) for asciminib (ABL001) in chronic myeloid leukemia (CML)...Priority Review granted based on positive data from the pivotal, Phase III ASCEMBL trial, where asciminib was compared to Bosulif® (bosutinib)* in patients with Philadelphia chromosome-positive CML in chronic phase (Ph+ CML-CP)...and data from a Phase I trial that included patients with Ph+ CML-CP harboring the T315I mutation.

Novartis today announced that asciminib....has been granted Breakthrough Therapy designation (BTD) by the US Food and Drug Administration (FDA) for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs). Asciminib was also granted BTD for the treatment of adult patients with Ph+ CML in CP harboring the T315I mutation.

...Patients with CML in chronic or accelerated phase who exhibit relapsed disease associated with the presence of the T315I "gatekeeper mutation" after at least one TKI are also eligible provided that no other effective therapy exists...

Asciminib demonstrated effectiveness in pts with CML and the T315I mutation in routine medical practice, including ponatinib pre-treated pts, a population with limited available treatment options. Effectiveness estimates were consistent with those observed in clinical trials. Although the number of pts was small, this global study reports on one of the largest cohorts of pts with CML and the T315I mutation.

Data from 24 T315I-positive CML patients in a 200 mg BID dose group were analyzed….Two-year overall survival at 24 months was 100%.

Two-years overall survival at 24 months was 100%. Survival rate without treatment discontinuation was 74%. CIF of CCyR, MMR and MR4 at 24 month was 57%, 57% and 34%, respectively….Highly pre-treated CML pts with T315I mutation are able to achieve a response with asciminib 200 mg BID,especially in ponatinib-naive group....Asciminib shows effectiveness in highly resistant pts with T315I mutation with/without other genetic events...

Pts with CML-CP with T315I were enrolled if treated with ≥1 prior TKI and no other effective therapy was available, provided informed consent, and received asciminib 200 mg BID....Asciminib monotherapy 200 mg BID exhibited a sustained, favorable safety profile after added exposure with no new safety signals in pts with CML-CP with T315I—a population with high unmet medical need. The clinical efficacy of asciminib is demonstrated by the high proportion of pts achieving durable MMR and BCR::ABL1IS ≤ 1%. The updated analysis confirms asciminib as a treatment option for pts with CML-CP with T315I, including those for whom treatment with PON has failed.

Asciminib 200 mg BID monotherapy continued to demonstrate a favorable safety profile and clinical efficacy in pts with CML-CP/AP harboring the T315I mutation, with durable MMR seen in almost half of the patients. Asciminib is a promising therapeutic option for pts with CML-CP/AP with T315I, including those for whom PON treatment has failed.

This phase 1 study (NCT02081378) enrolled pts ≥ 18 y old with CML in chronic phase (CP) or accelerated phase resistant to or intolerant of (R/I) ≥ 2 prior TKIs; pts carrying the T315I mut were eligible after ≥ 1 prior TKI. Enrolled pts carrying the T315I mut were assigned to asciminib 20 mg BID (1 pt), 40 mg BID (1 pt), 80 mg BID (4 pts), 150 mg BID (7 pts), 160 mg BID (7 pts), 200 mg BID (24 pts), 80 mg once daily (QD; 1 pt), 120 mg QD (4 pts), or 200 mg QD (1 pt) cohorts. We report results from the largest cohort: pts with confirmed T315I mut...Overall, asciminib 200 mg BID monotherapy showed a favorable safety profile and clinical efficacy in PON-naive and PON-R/I pts carrying the T315I mut.

In the dose-response matrix analysis (Fig. 1C), AXI treatment alone at 100 nM inhibited the growth of the K562/T315 mut cell line by 38.42%, and ASC treatment alone at 100 nM, by 36.52%. Of note, the combination of AXI at 25nM and ASC at 12.5nM inhibited cell growth by 38.1%, and the combination of AXI at 12.5nM and ASC at 25nM showed 38.42% inhibition, which is similar to the inhibition achieved by 100nM of each drug alone.