Vonjo
Generic: PACRITINIB
Basic Information
Manufacturer
Sobi, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
4b5ab444-0e1a-4984-99db-76ad11a298ee
Indications & Usage
1 INDICATIONS AND USAGE VONJO is indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF) with a platelet count below 50 × 10 9 /L.
This indication is approved under accelerated approval based on spleen volume reduction [see Clinical Studies ( 14 )] .
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
VONJO is a kinase inhibitor indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 10 9 /L ( 1 ).
This indication is approved under accelerated approval based on spleen volume reduction.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
This indication is approved under accelerated approval based on spleen volume reduction [see Clinical Studies ( 14 )] .
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
VONJO is a kinase inhibitor indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 10 9 /L ( 1 ).
This indication is approved under accelerated approval based on spleen volume reduction.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hemorrhage [see Warnings and Precautions ( 5.1 )] Diarrhea [see Warnings and Precautions ( 5.2 )] Thrombocytopenia [see Warnings and Precautions ( 5.3 )] Prolonged QT Interval [see Warnings and Precautions ( 5.4 )] Major Adverse Cardiac Events [see Warnings and Precautions ( 5.5 )] Thrombosis [see Warnings and Precautions ( 5.6 )] Secondary Malignancies [see Warnings and Precautions ( 5.7 )] Risk of Infection [see Warnings and Precautions ( 5.8 )] Symptom Exacerbation Following Interruption or Discontinuation of Treatment [see Warnings and Precautions ( 5.9 )] The most common (≥20% of patients) adverse reactions are diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema ( 6.1 ).
To report SUSPECTED ADVERSE REACTIONS, contact Sobi, Inc.
at (866) 773-5274 and www.VONJO.com 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.
PERSIST-2 Trial The safety of VONJO was evaluated in the randomized, controlled PERSIST-2 trial [see Clinical Studies ( 14 )] .
In PERSIST-2, key eligibility criteria included adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF with splenomegaly and a platelet count ≤100 × 10 9 /L.
Prior Janus associated kinase (JAK) inhibitor therapy was permitted.
Patients received VONJO at 200 mg twice daily (n=106), 400 mg once daily (n=104), or best available therapy (BAT) (n=98).
Forty-seven (44%) of the 106 patients treated with VONJO 200 mg twice daily had a baseline platelet count of <50 × 10 9 /L.
The 400 mg once daily dose could not be established to be safe, so further information on this arm is not provided.
In PERSIST-2, among the 106 patients treated with VONJO 200 mg twice daily, the median baseline hemoglobin was 9.7 g/dL and the median drug exposure was 25 weeks.
Fifty-four percent of patients were exposed for 6 months, and 18% were exposed for approximately 12 months.
Accounting for dose reductions, the average daily dose (mean relative dose intensity) and median daily dose (median relative dose intensity) were 380 mg (95%) and 400 mg (100%), respectively, for patients receiving VONJO twice daily.
The median age of patients who received VONJO 200 mg twice daily was 67 years (range: 39 to 85 years), 59% were male, 86% were White, 3% were Asian, 2% were Native Hawaiian or Other Pacific Islander, 0% were Black, 9% did not report race, and 87% had an Eastern Cooperative Oncology Group performance status of 0 to 1.
Serious adverse reactions occurred in 47% of patients treated with VONJO 200 mg twice daily and in 31% of patients treated with BAT.
The most frequent serious adverse reactions occurring in ≥3% patients receiving VONJO 200 mg twice daily were anemia (8%), thrombocytopenia (6%), pneumonia (6%), cardiac failure (4%), disease progression (3%), pyrexia (3%), and squamous cell carcinoma of skin (3%).
Fatal adverse reactions occurred in 8% of patients receiving VONJO 200 mg twice daily and in 9% of patients treated with BAT.
The fatal adverse reactions among patients treated with VONJO 200 mg twice daily included events of disease progression (3%), and multiorgan failure, cerebral hemorrhage, meningorrhagia, and acute myeloid leukemia in <1% of patients each, respectively.
Permanent discontinuation due to an adverse reaction occurred in 15% of patients receiving VONJO 200 mg twice daily compared to 12% of patients treated with BAT.
The most frequent reasons for permanent discontinuation in ≥2% of patients receiving VONJO 200 mg twice daily included anemia (3%) and thrombocytopenia (2%).
Drug interruptions due to an adverse reaction occurred in 27% of patients who received VONJO 200 mg twice daily compared to 10% of patients treated with BAT.
The most frequent reasons for drug interruption in ≥2% of patients receiving VONJO 200 mg twice daily were anemia (5%), thrombocytopenia (4%), diarrhea (3%), nausea (3%), cardiac failure (3%), neutropenia (2%), and pneumonia (2%).
Dosage reductions due to an adverse reaction occurred in 12% of patients who received VONJO 200 mg twice daily compared to 7% of patients treated with BAT.
Adverse reactions requiring dosage reduction in ≥2% of patients who received VONJO 200 mg twice daily included thrombocytopenia (2%), neutropenia (2%), conjunctival hemorrhage (2%), and epistaxis (2%).
The most common adverse reactions in ≥20% of patients (N=106) were diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema.
Table 5 summarizes the common adverse reactions in PERSIST-2 during randomized treatment.
Table 5 Adverse Reactions Reported in ≥10% Patients Receiving VONJO 200 mg Twice Daily or Best Available Therapy During Randomized Treatment in PERSIST-2 a Grade by CTCAE Version 4.03 Adverse Reactions VONJO (200 mg Twice Daily) (N=106) Best Available Therapy (N=98) All Grades a % Grade ≥3 % All Grades a % Grade ≥3 % Diarrhea 48 4 15 0 Thrombocytopenia 34 32 23 18 Nausea 32 1 11 1 Anemia 24 22 15 14 Peripheral edema 20 1 15 0 Vomiting 19 0 5 1 Dizziness 15 1 5 0 Pyrexia 15 1 3 0 Epistaxis 12 5 13 1 Dyspnea 10 0 9 3 Pruritus 10 2 6 0 Upper respiratory tract infection 10 0 6 0 Cough 8 2 10 0 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of VONJO.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Renal: Acute or subacute kidney injury (secondary to diarrhea) [see Warnings and Precautions (5.2)]
To report SUSPECTED ADVERSE REACTIONS, contact Sobi, Inc.
at (866) 773-5274 and www.VONJO.com 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.
PERSIST-2 Trial The safety of VONJO was evaluated in the randomized, controlled PERSIST-2 trial [see Clinical Studies ( 14 )] .
In PERSIST-2, key eligibility criteria included adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF with splenomegaly and a platelet count ≤100 × 10 9 /L.
Prior Janus associated kinase (JAK) inhibitor therapy was permitted.
Patients received VONJO at 200 mg twice daily (n=106), 400 mg once daily (n=104), or best available therapy (BAT) (n=98).
Forty-seven (44%) of the 106 patients treated with VONJO 200 mg twice daily had a baseline platelet count of <50 × 10 9 /L.
The 400 mg once daily dose could not be established to be safe, so further information on this arm is not provided.
In PERSIST-2, among the 106 patients treated with VONJO 200 mg twice daily, the median baseline hemoglobin was 9.7 g/dL and the median drug exposure was 25 weeks.
Fifty-four percent of patients were exposed for 6 months, and 18% were exposed for approximately 12 months.
Accounting for dose reductions, the average daily dose (mean relative dose intensity) and median daily dose (median relative dose intensity) were 380 mg (95%) and 400 mg (100%), respectively, for patients receiving VONJO twice daily.
The median age of patients who received VONJO 200 mg twice daily was 67 years (range: 39 to 85 years), 59% were male, 86% were White, 3% were Asian, 2% were Native Hawaiian or Other Pacific Islander, 0% were Black, 9% did not report race, and 87% had an Eastern Cooperative Oncology Group performance status of 0 to 1.
Serious adverse reactions occurred in 47% of patients treated with VONJO 200 mg twice daily and in 31% of patients treated with BAT.
The most frequent serious adverse reactions occurring in ≥3% patients receiving VONJO 200 mg twice daily were anemia (8%), thrombocytopenia (6%), pneumonia (6%), cardiac failure (4%), disease progression (3%), pyrexia (3%), and squamous cell carcinoma of skin (3%).
Fatal adverse reactions occurred in 8% of patients receiving VONJO 200 mg twice daily and in 9% of patients treated with BAT.
The fatal adverse reactions among patients treated with VONJO 200 mg twice daily included events of disease progression (3%), and multiorgan failure, cerebral hemorrhage, meningorrhagia, and acute myeloid leukemia in <1% of patients each, respectively.
Permanent discontinuation due to an adverse reaction occurred in 15% of patients receiving VONJO 200 mg twice daily compared to 12% of patients treated with BAT.
The most frequent reasons for permanent discontinuation in ≥2% of patients receiving VONJO 200 mg twice daily included anemia (3%) and thrombocytopenia (2%).
Drug interruptions due to an adverse reaction occurred in 27% of patients who received VONJO 200 mg twice daily compared to 10% of patients treated with BAT.
The most frequent reasons for drug interruption in ≥2% of patients receiving VONJO 200 mg twice daily were anemia (5%), thrombocytopenia (4%), diarrhea (3%), nausea (3%), cardiac failure (3%), neutropenia (2%), and pneumonia (2%).
Dosage reductions due to an adverse reaction occurred in 12% of patients who received VONJO 200 mg twice daily compared to 7% of patients treated with BAT.
Adverse reactions requiring dosage reduction in ≥2% of patients who received VONJO 200 mg twice daily included thrombocytopenia (2%), neutropenia (2%), conjunctival hemorrhage (2%), and epistaxis (2%).
The most common adverse reactions in ≥20% of patients (N=106) were diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema.
Table 5 summarizes the common adverse reactions in PERSIST-2 during randomized treatment.
Table 5 Adverse Reactions Reported in ≥10% Patients Receiving VONJO 200 mg Twice Daily or Best Available Therapy During Randomized Treatment in PERSIST-2 a Grade by CTCAE Version 4.03 Adverse Reactions VONJO (200 mg Twice Daily) (N=106) Best Available Therapy (N=98) All Grades a % Grade ≥3 % All Grades a % Grade ≥3 % Diarrhea 48 4 15 0 Thrombocytopenia 34 32 23 18 Nausea 32 1 11 1 Anemia 24 22 15 14 Peripheral edema 20 1 15 0 Vomiting 19 0 5 1 Dizziness 15 1 5 0 Pyrexia 15 1 3 0 Epistaxis 12 5 13 1 Dyspnea 10 0 9 3 Pruritus 10 2 6 0 Upper respiratory tract infection 10 0 6 0 Cough 8 2 10 0 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of VONJO.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Renal: Acute or subacute kidney injury (secondary to diarrhea) [see Warnings and Precautions (5.2)]