ENSACOVE
Generic: ENSARTINIB
Basic Information
Manufacturer
Xcovery Holdings, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
1e1b2f79-678a-472a-b924-66909c8a4b2e
Indications & Usage
1 INDICATIONS AND USAGE ENSACOVE is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC)as detected by an FDA-approved test [see Dosage and Administration ( 2.1 )] who have not previously received an ALK-inhibitor.
ENSACOVE is a kinase inhibitor indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test who have not previously received an ALK-inhibitor.
( 1 , 2.1 )
ENSACOVE is a kinase inhibitor indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test who have not previously received an ALK-inhibitor.
( 1 , 2.1 )
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions ( 5.1 )] Hepatoxicity [see Warnings and Precautions ( 5.2 )] Dermatologic Adverse Reactions [see Warnings and Precautions ( 5.3 )] Bradycardia [see Warnings and Precautions ( 5.4 )] Hyperglycemia [see Warnings and Precautions ( 5.5 )] Visual Disturbances [see Warnings and Precautions ( 5.6 )] Increased Creatine Phosphokinase [see Warnings and Precautions ( 5.7 )] Hyperuricemia [see Warnings and Precautions ( 5.8 )] FD&C Yellow No.
5 (Tartrazine) [see Warnings and Precautions ( 5.10 ) ] Most common adverse reactions (incidence ≥20%) were rash, musculoskeletal pain, constipation, pruritus, cough, nausea, edema, vomiting, fatigue, and pyrexia.
( 6.1 ) Most common Grade 3-4 laboratory abnormality (incidence ≥2%) were increased uric acid, decreased lymphocytes, increased alanine aminotransferase, decreased phosphate, increased gamma glutamyl transferase, increased magnesium, increased amylase, decreased sodium, increased glucose, decreased hemoglobin, increased bilirubin, decreased potassium, and increased creatine phosphokinase.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Xcovery Holdings, Inc.
at (866) 367-2268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The pooled safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to ENSACOVE as a single agent in 458 patients with locally advanced or metastatic ALK-positive NSCLC in the following trials: eXALT3 Study (N=143) [see Clinical Studies ( 14.1 ) ], Study 101 (NCT01625234, N=98), Study BTP-28311 (NCT02959619, N=35), and Study BTP-42322 (NCT03215693, N=182).
Patients received ENSACOVE 225 mg orally once daily, with or without food, until disease progression or unacceptable toxicity.
Among 458 patients who received ENSACOVE, 63% were exposed for 6 months or longer and 47% were exposed for greater than one year.
In this pooled safety population, the most common adverse reactions (≥20%) were rash, musculoskeletal pain, constipation, pruritus, cough, nausea, edema, vomiting, fatigue, and pyrexia.
The most frequent Grade 3 or 4 laboratory abnormalities (≥2%) were increased uric acid, decreased lymphocytes, increased alanine aminotransferase, decreased phosphate, increased gamma glutamyl transferase, increased magnesium, increased amylase, decreased sodium, increased glucose, decreased hemoglobin, increased bilirubin, decreased potassium, and increased creatine phosphokinase.
TKI-naive ALK-Positive Locally Advanced or Metastatic NSCLC The safety of ENSACOVE was evaluated in the eXALT3 study [see Clinical Studies ( 14.1 ) ].
Patients received ENSACOVE 225 mg orally once daily, with or without food, until disease progression or unacceptable toxicity .
Among patients who received ENSACOVE, 78% were exposed for 6 months or longer and 66% were exposed for greater than one year.
The median age of patients who received ENSACOVE was 54 years (range: 25-86); 50% male; 54% Asian, 43% White; 0.7% Black or African American; and 11% Hispanic or Latino.
Serious adverse reactions occurred in 23% of patients treated with ENSACOVE.
Serious adverse reactions that occurred in ≥1% were pneumonia (4.9%), hemorrhage (2.1%), rash (2.1%) and cellulitis (1.4%).
One fatal adverse reaction (0.7%) occurred due to bronchopneumonia.
Permanent discontinuation of ENSACOVE due to an adverse reaction occurred in 12% of patients.
Adverse reactions which resulted in permanent discontinuation of ENSACOVE (≥1%) included increased blood bilirubin (1.4%), increased conjugated bilirubin (1.4%), increased ALT (2.1%), increased AST (2.1%), and pneumonitis/ILD (2.1%).
Dose interruptions of ENSACOVE due to an adverse reaction occurred in 41% of patients.
Adverse reactions which required dose interruptions (≥2%) included rash (13%), increased ALT (6%), edema (2.8%), pruritus (2.8%), pyrexia (2.8%), pneumonia (3.5%), increased AST (2.1%), hemorrhage (2.1%), and decreased appetite (2.1%).
Dose reductions of ENSACOVE due to an adverse reaction occurred in 24% of patients.
Adverse reactions which required dose reductions (≥2%) included rash (11%), increased ALT (4.2%), pruritus (2.8%), and edema (2.1%).
Tables 3 and 4 summarize the most frequent adverse reactions and laboratory abnormalities, respectively.
Table 3: Adverse Reactions ( ≥10%) in Patients with ALK-Positive Locally Advanced or Metastatic NSCLC Who Received ENSACOVE in eXALT3 Study ENSACOVE N = 143 Crizotinib N = 146 Adverse Reaction All Grades % Grade 3 or 4 % All Grades % Grade 3 or 4 % Skin and Subcutaneous Tissue Disorders Rash a 66 12 10 0 Pruritus b 30 2.1 4.1 0 Alopecia 11 0 4.8 0 Dry Skin 10 0.7 0.7 0 Musculoskeletal and Connective Tissue Disorders Musculoskeletal Pain c 36 1.4 20 0 Respiratory, Thoracic and Mediastinal Disorders Cough d 31 0.7 16 0 Gastrointestinal Disorders Constipation 31 0 26 0 Nausea 28 1.4 30 2.1 Vomiting e 16 0.7 32 0 General Disorders and Administration Site Conditions Edema f 27 2.1 28 2.1 Pyrexia g 22 0.7 10 0.7 Fatigue h 21 0.7 14 1.4 Metabolism and Nutrition Disorders Decreased appetite 15 0 12 1.4 Infection and Infestation Respiratory Tract Infection 13 0.7 10 0 Nervous System Disorders Dizziness i 12 0.7 14 0.7 Dysgeusia 10 0 11 0 Vascular Disorders Hemorrhage j 10 1.4 4.8 0 Adverse reactions were graded using NCI CTCAE version 4.03.
a Includes dermatitis, dermatitis acneiform, dermatitis bullous, drug eruption, eczema, exfoliative rash, palmar-plantar erythrodysaesthesia, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic, rash pustular, skin exfoliation, and vulvovaginal rash b Includes ear pruritus, eye pruritus, eyelids pruritus, lip pruritus, pruritus, and pruritus generalized c Includes arthritis, spinal pain, myalgia, musculoskeletal pain, back pain, pain in extremity, neck pain, arthralgia, non-cardiac chest pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort d Includes cough, productive cough, upper-airway cough syndrome e Includes vomiting and retching f Includes eyelid edema, face edema, generalized edema, localized edema, edema, edema peripheral, gravitational edema, skin edema, eye edema, and periorbital edema g Includes pyrexia and hyperthermia h Includes fatigue and asthenia i Includes dizziness, vertigo, postural dizziness j Includes hemoptysis, intracranial hemorrhage, gastrointestinal hemorrhage, hematuria, upper gastrointestinal hemorrhage, vaginal hemorrhage, gingival bleeding, vitreous hemorrhage, epistaxis, rectal hemorrhage, anal hemorrhage Table 4: Select Laboratory Abnormalities (≥20%) That Worsened from Baseline in Patients with ALK-Positive Locally Advanced or Metastatic NSCLC Who Received ENSACOVE in eXALT3 Study ENSACOVE N = 143 Crizotinib N = 146 Lab Abnormality All Grades % Grade 3 or 4 % All Grades % Grade 3 or 4 % Chemistry Alanine aminotransferase increased 73 5 74 8 Alkaline phosphatase increased 64 2.2 50 0.7 Aspartate aminotransferase increased 64 1.4 62 3.5 Glucose increased 49 5 35 0.7 Albumin decreased 46 0.7 56 1.4 Phosphate decreased 39 7 42 4.9 Urate increased 39 39 27 27 Creatinine increased 37 0 27 0 Calcium decreased 36 1.4 64 4.9 Sodium decreased 27 4.3 27 4.2 Hematology Lymphocytes decreased 57 7 47 5 Hemoglobin decreased 43 0.7 31 1.4 Adverse reactions were graded using NCI CTCAE version 4.03.
ALT = Alanine aminotransferase; AST = Aspartate aminotransferase Clinically relevant adverse reactions in <10% of patients who received ENSACOVE included interstitial lung disease, photosensitivity, increased creatinine phosphokinase, bradycardia, and visual disturbances.
5 (Tartrazine) [see Warnings and Precautions ( 5.10 ) ] Most common adverse reactions (incidence ≥20%) were rash, musculoskeletal pain, constipation, pruritus, cough, nausea, edema, vomiting, fatigue, and pyrexia.
( 6.1 ) Most common Grade 3-4 laboratory abnormality (incidence ≥2%) were increased uric acid, decreased lymphocytes, increased alanine aminotransferase, decreased phosphate, increased gamma glutamyl transferase, increased magnesium, increased amylase, decreased sodium, increased glucose, decreased hemoglobin, increased bilirubin, decreased potassium, and increased creatine phosphokinase.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Xcovery Holdings, Inc.
at (866) 367-2268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The pooled safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to ENSACOVE as a single agent in 458 patients with locally advanced or metastatic ALK-positive NSCLC in the following trials: eXALT3 Study (N=143) [see Clinical Studies ( 14.1 ) ], Study 101 (NCT01625234, N=98), Study BTP-28311 (NCT02959619, N=35), and Study BTP-42322 (NCT03215693, N=182).
Patients received ENSACOVE 225 mg orally once daily, with or without food, until disease progression or unacceptable toxicity.
Among 458 patients who received ENSACOVE, 63% were exposed for 6 months or longer and 47% were exposed for greater than one year.
In this pooled safety population, the most common adverse reactions (≥20%) were rash, musculoskeletal pain, constipation, pruritus, cough, nausea, edema, vomiting, fatigue, and pyrexia.
The most frequent Grade 3 or 4 laboratory abnormalities (≥2%) were increased uric acid, decreased lymphocytes, increased alanine aminotransferase, decreased phosphate, increased gamma glutamyl transferase, increased magnesium, increased amylase, decreased sodium, increased glucose, decreased hemoglobin, increased bilirubin, decreased potassium, and increased creatine phosphokinase.
TKI-naive ALK-Positive Locally Advanced or Metastatic NSCLC The safety of ENSACOVE was evaluated in the eXALT3 study [see Clinical Studies ( 14.1 ) ].
Patients received ENSACOVE 225 mg orally once daily, with or without food, until disease progression or unacceptable toxicity .
Among patients who received ENSACOVE, 78% were exposed for 6 months or longer and 66% were exposed for greater than one year.
The median age of patients who received ENSACOVE was 54 years (range: 25-86); 50% male; 54% Asian, 43% White; 0.7% Black or African American; and 11% Hispanic or Latino.
Serious adverse reactions occurred in 23% of patients treated with ENSACOVE.
Serious adverse reactions that occurred in ≥1% were pneumonia (4.9%), hemorrhage (2.1%), rash (2.1%) and cellulitis (1.4%).
One fatal adverse reaction (0.7%) occurred due to bronchopneumonia.
Permanent discontinuation of ENSACOVE due to an adverse reaction occurred in 12% of patients.
Adverse reactions which resulted in permanent discontinuation of ENSACOVE (≥1%) included increased blood bilirubin (1.4%), increased conjugated bilirubin (1.4%), increased ALT (2.1%), increased AST (2.1%), and pneumonitis/ILD (2.1%).
Dose interruptions of ENSACOVE due to an adverse reaction occurred in 41% of patients.
Adverse reactions which required dose interruptions (≥2%) included rash (13%), increased ALT (6%), edema (2.8%), pruritus (2.8%), pyrexia (2.8%), pneumonia (3.5%), increased AST (2.1%), hemorrhage (2.1%), and decreased appetite (2.1%).
Dose reductions of ENSACOVE due to an adverse reaction occurred in 24% of patients.
Adverse reactions which required dose reductions (≥2%) included rash (11%), increased ALT (4.2%), pruritus (2.8%), and edema (2.1%).
Tables 3 and 4 summarize the most frequent adverse reactions and laboratory abnormalities, respectively.
Table 3: Adverse Reactions ( ≥10%) in Patients with ALK-Positive Locally Advanced or Metastatic NSCLC Who Received ENSACOVE in eXALT3 Study ENSACOVE N = 143 Crizotinib N = 146 Adverse Reaction All Grades % Grade 3 or 4 % All Grades % Grade 3 or 4 % Skin and Subcutaneous Tissue Disorders Rash a 66 12 10 0 Pruritus b 30 2.1 4.1 0 Alopecia 11 0 4.8 0 Dry Skin 10 0.7 0.7 0 Musculoskeletal and Connective Tissue Disorders Musculoskeletal Pain c 36 1.4 20 0 Respiratory, Thoracic and Mediastinal Disorders Cough d 31 0.7 16 0 Gastrointestinal Disorders Constipation 31 0 26 0 Nausea 28 1.4 30 2.1 Vomiting e 16 0.7 32 0 General Disorders and Administration Site Conditions Edema f 27 2.1 28 2.1 Pyrexia g 22 0.7 10 0.7 Fatigue h 21 0.7 14 1.4 Metabolism and Nutrition Disorders Decreased appetite 15 0 12 1.4 Infection and Infestation Respiratory Tract Infection 13 0.7 10 0 Nervous System Disorders Dizziness i 12 0.7 14 0.7 Dysgeusia 10 0 11 0 Vascular Disorders Hemorrhage j 10 1.4 4.8 0 Adverse reactions were graded using NCI CTCAE version 4.03.
a Includes dermatitis, dermatitis acneiform, dermatitis bullous, drug eruption, eczema, exfoliative rash, palmar-plantar erythrodysaesthesia, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic, rash pustular, skin exfoliation, and vulvovaginal rash b Includes ear pruritus, eye pruritus, eyelids pruritus, lip pruritus, pruritus, and pruritus generalized c Includes arthritis, spinal pain, myalgia, musculoskeletal pain, back pain, pain in extremity, neck pain, arthralgia, non-cardiac chest pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort d Includes cough, productive cough, upper-airway cough syndrome e Includes vomiting and retching f Includes eyelid edema, face edema, generalized edema, localized edema, edema, edema peripheral, gravitational edema, skin edema, eye edema, and periorbital edema g Includes pyrexia and hyperthermia h Includes fatigue and asthenia i Includes dizziness, vertigo, postural dizziness j Includes hemoptysis, intracranial hemorrhage, gastrointestinal hemorrhage, hematuria, upper gastrointestinal hemorrhage, vaginal hemorrhage, gingival bleeding, vitreous hemorrhage, epistaxis, rectal hemorrhage, anal hemorrhage Table 4: Select Laboratory Abnormalities (≥20%) That Worsened from Baseline in Patients with ALK-Positive Locally Advanced or Metastatic NSCLC Who Received ENSACOVE in eXALT3 Study ENSACOVE N = 143 Crizotinib N = 146 Lab Abnormality All Grades % Grade 3 or 4 % All Grades % Grade 3 or 4 % Chemistry Alanine aminotransferase increased 73 5 74 8 Alkaline phosphatase increased 64 2.2 50 0.7 Aspartate aminotransferase increased 64 1.4 62 3.5 Glucose increased 49 5 35 0.7 Albumin decreased 46 0.7 56 1.4 Phosphate decreased 39 7 42 4.9 Urate increased 39 39 27 27 Creatinine increased 37 0 27 0 Calcium decreased 36 1.4 64 4.9 Sodium decreased 27 4.3 27 4.2 Hematology Lymphocytes decreased 57 7 47 5 Hemoglobin decreased 43 0.7 31 1.4 Adverse reactions were graded using NCI CTCAE version 4.03.
ALT = Alanine aminotransferase; AST = Aspartate aminotransferase Clinically relevant adverse reactions in <10% of patients who received ENSACOVE included interstitial lung disease, photosensitivity, increased creatinine phosphokinase, bradycardia, and visual disturbances.