Safety Profile

SAFETY PROFILE IN PATIENTS AFTER 2 TKIs

For adults with Ph+ CML-CP, previously treated with ≥2 TKIs more patients were able to stay on SCEMBLIX¹

Discontinuation rate due to adverse reactions was more than 3 times lower with SCEMBLIX vs bosutinib.^1,2

• 6% of patients on SCEMBLIX (n=10/156) required dose reduction due to adverse reactions vs 28% on bosutinib (n=21/76)^1,3

• 41% of patients on SCEMBLIX (n=64/156) required dose interruption due to adverse reactions vs 58% on bosutinib (n=44/76)^1,3

Well-established tolerability profile over time¹

Serious adverse reactions occurred in 18% of patients who received SCEMBLIX. Serious adverse reactions in ≥1% included cardiac failure congestive (1.9%), pyrexia (1.9%), urinary tract infection (1.9%), headache (1.3%), and thrombocytopenia (1.3%). Two patients (1.3%) had a fatal adverse reaction, one each for mesenteric artery thrombosis and ischemic stroke.¹ 

ARs, adverse reactions; URTI, upper respiratory tract infection.

^aURTI includes: nasopharyngitis, upper respiratory infection, rhinitis, pharyngitis, respiratory tract infection, and pharyngotonsillitis.
^bMusculoskeletal pain includes: pain in extremity, back pain, myalgia, non-cardiac chest pain, neck pain, bone pain, spinal pain, arthritis, musculoskeletal pain, and musculoskeletal chest pain.
^cHeadache includes: headache and post-traumatic headache.
^dFatigue includes: fatigue and asthenia.
^eRash includes: rash, rash maculopapular, dermatitis acneiform, rash pustular, eczema, dermatitis, skin exfoliation, dermatitis exfoliative generalized, rash morbilliform, drug eruption, erythema multiform, and rash erythematous.
^fHypertension includes: hypertension and hypertensive crisis.
^gAbdominal pain includes: abdominal pain, abdominal pain upper, abdominal discomfort, abdominal pain lower, abdominal tenderness, and epigastric discomfort.
^hDiarrhea includes: diarrhea and colitis.

Laboratory abnormalities

ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase.

ⁱThe denominator used to calculate the rate for SCEMBLIX and bosutinib varied from 152 to 156 and 75 to 76, respectively, based on the number of patients with a baseline value and at least 1 post-treatment value.

Exposure-adjusted incidence rates of adverse events with SCEMBLIX and bosutinib⁴

Limitation: Exposure-adjusted incidence rate (EAIR) analysis is utilized when there is a difference in exposure between 2 arms or 2 studies. The exposure-adjusted rates assume the probability that an adverse event will happen is constant over time, which is not always true.

The median duration of exposure was 24 months (range: 0 to 46 months) for patients receiving SCEMBLIX and 7 months (range: 0 to 43 months) for patients receiving bosutinib.⁴

As a result of the higher treatment discontinuation rate in the bosutinib arm, the duration of exposure to SCEMBLIX and bosutinib differed. Incidence per 100 PTY is a measurement that compares the adverse event incidence rates between the 2 groups (268.9 PTY vs 72.9 with SCEMBLIX and bosutinib, respectively) while adjusting for this imbalance in duration.

Adverse events of special interest (AESIs) were the AEs that represent the group of AEs with specific interest when patients are being treated with study drug. These AEs were defined based on the class effects of other TKIs in the same class, mechanism of action, and the current preclinical and clinical knowledge of the study drug. The AESIs related to SCEMBLIX are: myelosuppression, pancreatic toxicity, hypersensitivity, hepatotoxicity, hepatitis B reactivation, reproductive toxicity, GI toxicity, phototoxicity, QTc prolongation, cardiac failure, edema and fluid retention, ischemic heart disease and CNS conditions, AOEs, and hemorrhage.

Dose reductions for SCEMBLIX: hypersensitivity 1 (0.6%). Dose reductions for bosutinib: edema and fluid retention 1 (1.3%); GI toxicity 10 (13.2%), hepatotoxicity 3 (3.9%); hypersensitivity 3 (3.9%).²

AEs, adverse events; AOEs, arterial occlusive events; CNS, central nervous system; EAIRs, exposure-adjusted incidence rates; GI, gastrointestinal; PTY, patient-treatment years.

^jBased on the safety analysis set. Numbers represent counts of patients. Other adverse events of special interest, such as hepatitis B virus reaction, hepatotoxicity (clinical events), pancreatic toxicity (clinical events), and phototoxicity, were not reported.^4
kAdverse events of special interest are reported as grouped adverse reactions.^4
lGI toxicity includes diarrhea, nausea, abdominal pain, vomiting, constipation, noncardiac chest pain, abdominal pain upper, abdominal distension, abdominal pain lower, abdominal tenderness, epigastric discomfort, flatulence, and abdominal discomfort.^2
mIncludes ARs related to laboratory value abnormalities.^4
nIncludes the preferred terms rash, rash maculopapular, dermatitis acneiform, periorbital edema, rash pustular, rhinitis allergic, urticaria, allergic transfusion reaction, dermatitis, dermatitis allergic, dermatitis contact, dermatitis exfoliative generalized, eczema, rash morbilliform, drug eruption, erythema multiforme, eyelid edema, face edema, hand dermatitis, hypersensitivity, and rash erythematous.^4
oIncluded 2 events of maternal exposure during pregnancy (with a spontaneous abortion reported in one case) with asciminib and 2 diagnoses (after informed consent) of congenital cardiovascular anomaly that were not resolved—1 each with asciminib and bosutinib.⁴

Incidence of first-ever adverse events with SCEMBLIX and bosutinib^2,4

Denominator is the number of subjects at the beginning of the interval who have not yet experienced the event. A subject with multiple occurrences of an AE with the same preferred term within the same time interval under one treatment is counted only once in that time interval for that treatment.

Thrombocytopenia, Neutropenia, and Erythropenia are group terms.

View the SCEMBLIX patient profiles >

SAFETY PROFILE IN PATIENTS WITH THE T315I MUTATION

For adult patients with Ph+ CML-CP with the T315I mutation¹

Serious adverse reactions occurred in 23% of patients who received SCEMBLIX. Serious adverse reactions in >1% included abdominal pain (4.2%), vomiting (4.2%), pneumonia (4.2%), musculoskeletal pain (2.1%), headache (2.1%), hemorrhage (2.1%), constipation (2.1%), arrhythmia (2.1%), and pleural effusion (2.1%).¹