BESREMi
Generic: ROPEGINTERFERON ALFA-2B
Basic Information
Manufacturer
PharmaEssentia USA
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
9583405d-53a0-49dc-88eb-5e6384ebabcb
Indications & Usage
1 INDICATIONS AND USAGE BESREMi is indicated for the treatment of adults with polycythemia vera.
BESREMi is an interferon alfa-2b indicated for the treatment of adults with polycythemia vera ( 1 )
BESREMi is an interferon alfa-2b indicated for the treatment of adults with polycythemia vera ( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling.
Depression and Suicide [see Warnings and Precautions (5.1)] Endocrine Toxicity [see Warnings and Precautions (5.2)] Cardiovascular Toxicity [see Warnings and Precautions (5.3)] Decreased Peripheral Blood Counts [see Warnings and Precautions (5.4)] Hypersensitivity Reactions [see Warnings and Precautions (5.5)] Pancreatitis [see Warnings and Precautions (5.6)] Colitis [see Warnings and Precautions (5.7)] Pulmonary Toxicity [see Warnings and Precautions (5.8)] Ophthalmologic Toxicity [see Warnings and Precautions (5.9)] Hyperlipidemia [see Warnings and Precautions (5.10)] Hepatotoxicity [see Warnings and Precautions (5.11)] Renal Toxicity [see Warnings and Precautions (5.12)] Dental and Periodontal Toxicity [see Warnings and Precautions (5.13)] Dermatologic Toxicity [see Warnings and Precautions (5.14)] Driving and Operating Machinery [see Warnings and Precautions (5.15)] 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 section reflects exposure to BESREMi as monotherapy for the treatment of polycythemia vera dosed every two to four weeks in 178 patients in two open-label trials [PEGINVERA, PROUD/CONTINUATION PV].
The mean age at baseline was 58.6 years (range 30-85 years), 88 (49.4%) women, 90 (50.6%) men, 177 (99%) Caucasian and 1 (1%) Asian.
Among 178 patients who received BESREMi, 80% were exposed for 12 months or longer.
The mean dose of BESREMi was 334 mcg SD ± 121 during the treatment period.
In this pooled safety population, the most common adverse reactions greater than 10%, were liver enzyme elevations (20%), leukopenia (20%), thrombocytopenia (19%), arthralgia (13%), fatigue (12%), myalgia (11%), and influenza-like illness (11%).
The safety findings described below reflect exposure to BESREMi as monotherapy for the treatment of polycythemia vera in 51 patients in the PEGINVERA study [see Clinical Studies (14) ].
Among the 51 patients receiving BESREMi, 71% were exposed for 12 months or longer, 63% were exposed for three years or longer, and 53% were exposed for greater than five years.
Serious adverse reactions were reported in 16% of patients in the PEGINVERA study.
The most common serious adverse reactions observed during the study (> 4%) included urinary tract infection (8%), transient ischemic attack (6%) and depression (4%).
Adverse reactions requiring permanent discontinuation in >2% of patients who received BESREMi included depression (8%) arthralgia (4%), fatigue (4%), and general physical health deterioration (4%) In the PEGINVERA study, patients were not pre-screened for depression or anxiety disorders.
The most common adverse reactions reported in ≥10% of patients in the PEGINVERA study are listed in Table 2.
Table 2 Adverse Reactions in > 10% of Subjects with Polycythemia Vera in the PEGINVERA Study Over 7.5 Years.
Adverse Reactions* BESREMi N=51 % Influenza-like illness a 59 Arthralgia 47 Fatigue b 47 Pruritis 45 Nasopharyngitis c 43 Musculoskeletal pain d 41 Headache e 39 Diarrhea 33 Hyperhidrosis f 29 Nausea 28 Upper respiratory tract infection g 27 Local administration site reactions 26 Dizziness 22 Abdominal pain h 20 Depression 20 Sleep disorder i 20 Leukopenia 18 Decreased appetite 18 Alopecia 16 Edema j 16 Hypertension k 16 Muscle spasms 16 Neutropenia 16 Rash l 16 Transaminase elevations m 16 Urinary tract infection 16 Thrombocytopenia 12 Vertigo 12 *Adverse Reactions defined as all treatment emergent adverse events Grouped Term Definitions a Includes pyrexia, chills, and influenza-like illness.
b Includes asthenia, malaise, and fatigue.
c Includes pharyngitis and nasopharyngitis.
d Includes musculoskeletal pain, back pain, pain in extremity, bone pain, flank pain, and spinal pain.
e Includes headache, migraine, and head pain.
f Includes night sweats and hyperhidrosis.
g Includes upper respiratory tract infection, rhinitis, bronchitis, and respiratory tract infection.
h Includes abdominal pain upper, abdominal pain lower, and abdominal pain.
i Includes insomnia, sleep disorder, and abnormal dreams.
j Includes peripheral edema and generalized edema.
k Includes hypertension and hypertensive crisis.
l Includes rash, maculopapular rash, and pruritic rash.
m Includes transaminase increase, hepatic enzyme increase, GGT increase, AST increase, and ALT increase.
Cardiovascular System : Atrial fibrillation The most common adverse reactions reported in > 40% of patients were influenza-like illness, arthralgia, fatigue, pruritus, nasopharyngitis, and musculoskeletal pain ( 6 ).
To report SUSPECTED ADVERSE REACTIONS, contact PharmaEssentia at 1-800-999-2449 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience The following clinically significant adverse reactions are described elsewhere in the labeling.
Depression and Suicide [see Warnings and Precautions (5.1) ] Endocrine Toxicity [see Warnings and Precautions (5.2) ] Cardiovascular Toxicity [see Warnings and Precautions (5.3) ] Decreased Peripheral Blood Counts [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Pancreatitis [see Warnings and Precautions (5.6) ] Colitis [see Warnings and Precautions (5.7) ] Pulmonary Toxicity [see Warnings and Precautions (5.8) ] Ophthalmologic Toxicity [see Warnings and Precautions (5.9) ] Hyperlipidemia [see Warnings and Precautions (5.10) ] Hepatotoxicity [see Warnings and Precautions (5.11) ] Renal Toxicity [see Warnings and Precautions (5.12) ] Dental and Periodontal Toxicity [see Warnings and Precautions (5.13) ] Dermatologic Toxicity [see Warnings and Precautions (5.14) ] Driving and Operating Machinery [see Warnings and Precautions (5.15) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.16) ] 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 section reflects exposure to BESREMi as monotherapy for the treatment of polycythemia vera dosed every two to four weeks in 178 patients in two open-label trials [ PEGINVERA, PROUD/CONTINUATION PV ].
The mean age at baseline was 58.6 years (range 30-85 years), 88 (49.4%) women, 90 (50.6%) men, 177 (99%) Caucasian and 1 (1%) Asian.
Among 178 patients who received BESREMi, 80% were exposed for 12 months or longer.
The mean dose of BESREMi was 334 mcg SD ± 121 during the treatment period.
In this pooled safety population, the most common adverse reactions greater than 10%, were liver enzyme elevations (20%), leukopenia (20%), thrombocytopenia (19%), arthralgia (13%), fatigue (12%), myalgia (11%), and influenza-like illness (11%).
The safety findings described below reflect exposure to BESREMi as monotherapy for the treatment of polycythemia vera in 51 patients in the PEGINVERA study [see Clinical Studies (14) ] .
Among the 51 patients receiving BESREMi, 71% were exposed for 12 months or longer, 63% were exposed for three years or longer, and 53% were exposed for greater than five years.
Serious adverse reactions were reported in 16% of patients in the PEGINVERA study.
The most common serious adverse reactions observed during the study (≥ 4%) included urinary tract infection (8%), transient ischemic attack (6%) and depression (4%).
Adverse reactions requiring permanent discontinuation in >2% of patients who received BESREMi included depression (8%), arthralgia (4%), fatigue (4%), and general physical health deterioration (4%) In the PEGINVERA study, patients were not pre-screened for depression or anxiety disorders.
The most common adverse reactions reported in ≥10% of patients in the PEGINVERA study are listed in Table 2.
Table 2 Adverse Reactions in > 10% of Subjects with Polycythemia Vera in the PEGINVERA Study Over 7.5 Years.
Adverse Reactions Adverse Reactions defined as all treatment emergent adverse events BESREMi N=51 % Grouped Term Definitions Influenza-like illness Includes pyrexia, chills, and influenza-like illness.
59 Arthralgia 47 Fatigue Includes asthenia, malaise, and fatigue.
47 Pruritis 45 Nasopharyngitis Includes pharyngitis and nasopharyngitis.
43 Musculoskeletal pain Includes musculoskeletal pain, back pain, pain in extremity, bone pain, flank pain, and spinal pain.
41 Headache Includes headache, migraine, and head pain.
39 Diarrhea 33 Hyperhidrosis Includes night sweats and hyperhidrosis.
29 Nausea 28 Upper respiratory tract infection Includes upper respiratory tract infection, rhinitis, bronchitis, and respiratory tract infection.
27 Local administration site reactions 26 Dizziness 22 Abdominal pain Includes abdominal pain upper, abdominal pain lower, and abdominal pain.
20 Depression 20 Sleep disorder Includes insomnia, sleep disorder, and abnormal dreams.
20 Leukopenia 18 Decreased appetite 18 Alopecia 16 Edema Includes peripheral edema and generalized edema.
16 Hypertension Includes hypertension and hypertensive crisis.
16 Muscle spasms 16 Neutropenia 16 Rash Includes rash, maculopapular rash, and pruritic rash.
16 Transaminase elevations Includes transaminase increase, hepatic enzyme increase, GGT increase, AST increase, and ALT increase.
16 Urinary tract infection 16 Thrombocytopenia 12 Vertigo 12 Clinically relevant adverse reactions in < 10% of patients include: Cardiovascular System: Atrial fibrillation 6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other interferon alfa-2b products may be misleading.
The incidence of binding antibodies to ropeginterferon alfa-2b-njft was 1.4% (2/146) and they were observed as early as 8 weeks post-dosing.
Among the patients who tested positive for binding antibodies, none developed neutralizing antibodies.
Depression and Suicide [see Warnings and Precautions (5.1)] Endocrine Toxicity [see Warnings and Precautions (5.2)] Cardiovascular Toxicity [see Warnings and Precautions (5.3)] Decreased Peripheral Blood Counts [see Warnings and Precautions (5.4)] Hypersensitivity Reactions [see Warnings and Precautions (5.5)] Pancreatitis [see Warnings and Precautions (5.6)] Colitis [see Warnings and Precautions (5.7)] Pulmonary Toxicity [see Warnings and Precautions (5.8)] Ophthalmologic Toxicity [see Warnings and Precautions (5.9)] Hyperlipidemia [see Warnings and Precautions (5.10)] Hepatotoxicity [see Warnings and Precautions (5.11)] Renal Toxicity [see Warnings and Precautions (5.12)] Dental and Periodontal Toxicity [see Warnings and Precautions (5.13)] Dermatologic Toxicity [see Warnings and Precautions (5.14)] Driving and Operating Machinery [see Warnings and Precautions (5.15)] 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 section reflects exposure to BESREMi as monotherapy for the treatment of polycythemia vera dosed every two to four weeks in 178 patients in two open-label trials [PEGINVERA, PROUD/CONTINUATION PV].
The mean age at baseline was 58.6 years (range 30-85 years), 88 (49.4%) women, 90 (50.6%) men, 177 (99%) Caucasian and 1 (1%) Asian.
Among 178 patients who received BESREMi, 80% were exposed for 12 months or longer.
The mean dose of BESREMi was 334 mcg SD ± 121 during the treatment period.
In this pooled safety population, the most common adverse reactions greater than 10%, were liver enzyme elevations (20%), leukopenia (20%), thrombocytopenia (19%), arthralgia (13%), fatigue (12%), myalgia (11%), and influenza-like illness (11%).
The safety findings described below reflect exposure to BESREMi as monotherapy for the treatment of polycythemia vera in 51 patients in the PEGINVERA study [see Clinical Studies (14) ].
Among the 51 patients receiving BESREMi, 71% were exposed for 12 months or longer, 63% were exposed for three years or longer, and 53% were exposed for greater than five years.
Serious adverse reactions were reported in 16% of patients in the PEGINVERA study.
The most common serious adverse reactions observed during the study (> 4%) included urinary tract infection (8%), transient ischemic attack (6%) and depression (4%).
Adverse reactions requiring permanent discontinuation in >2% of patients who received BESREMi included depression (8%) arthralgia (4%), fatigue (4%), and general physical health deterioration (4%) In the PEGINVERA study, patients were not pre-screened for depression or anxiety disorders.
The most common adverse reactions reported in ≥10% of patients in the PEGINVERA study are listed in Table 2.
Table 2 Adverse Reactions in > 10% of Subjects with Polycythemia Vera in the PEGINVERA Study Over 7.5 Years.
Adverse Reactions* BESREMi N=51 % Influenza-like illness a 59 Arthralgia 47 Fatigue b 47 Pruritis 45 Nasopharyngitis c 43 Musculoskeletal pain d 41 Headache e 39 Diarrhea 33 Hyperhidrosis f 29 Nausea 28 Upper respiratory tract infection g 27 Local administration site reactions 26 Dizziness 22 Abdominal pain h 20 Depression 20 Sleep disorder i 20 Leukopenia 18 Decreased appetite 18 Alopecia 16 Edema j 16 Hypertension k 16 Muscle spasms 16 Neutropenia 16 Rash l 16 Transaminase elevations m 16 Urinary tract infection 16 Thrombocytopenia 12 Vertigo 12 *Adverse Reactions defined as all treatment emergent adverse events Grouped Term Definitions a Includes pyrexia, chills, and influenza-like illness.
b Includes asthenia, malaise, and fatigue.
c Includes pharyngitis and nasopharyngitis.
d Includes musculoskeletal pain, back pain, pain in extremity, bone pain, flank pain, and spinal pain.
e Includes headache, migraine, and head pain.
f Includes night sweats and hyperhidrosis.
g Includes upper respiratory tract infection, rhinitis, bronchitis, and respiratory tract infection.
h Includes abdominal pain upper, abdominal pain lower, and abdominal pain.
i Includes insomnia, sleep disorder, and abnormal dreams.
j Includes peripheral edema and generalized edema.
k Includes hypertension and hypertensive crisis.
l Includes rash, maculopapular rash, and pruritic rash.
m Includes transaminase increase, hepatic enzyme increase, GGT increase, AST increase, and ALT increase.
Cardiovascular System : Atrial fibrillation The most common adverse reactions reported in > 40% of patients were influenza-like illness, arthralgia, fatigue, pruritus, nasopharyngitis, and musculoskeletal pain ( 6 ).
To report SUSPECTED ADVERSE REACTIONS, contact PharmaEssentia at 1-800-999-2449 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience The following clinically significant adverse reactions are described elsewhere in the labeling.
Depression and Suicide [see Warnings and Precautions (5.1) ] Endocrine Toxicity [see Warnings and Precautions (5.2) ] Cardiovascular Toxicity [see Warnings and Precautions (5.3) ] Decreased Peripheral Blood Counts [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Pancreatitis [see Warnings and Precautions (5.6) ] Colitis [see Warnings and Precautions (5.7) ] Pulmonary Toxicity [see Warnings and Precautions (5.8) ] Ophthalmologic Toxicity [see Warnings and Precautions (5.9) ] Hyperlipidemia [see Warnings and Precautions (5.10) ] Hepatotoxicity [see Warnings and Precautions (5.11) ] Renal Toxicity [see Warnings and Precautions (5.12) ] Dental and Periodontal Toxicity [see Warnings and Precautions (5.13) ] Dermatologic Toxicity [see Warnings and Precautions (5.14) ] Driving and Operating Machinery [see Warnings and Precautions (5.15) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.16) ] 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 section reflects exposure to BESREMi as monotherapy for the treatment of polycythemia vera dosed every two to four weeks in 178 patients in two open-label trials [ PEGINVERA, PROUD/CONTINUATION PV ].
The mean age at baseline was 58.6 years (range 30-85 years), 88 (49.4%) women, 90 (50.6%) men, 177 (99%) Caucasian and 1 (1%) Asian.
Among 178 patients who received BESREMi, 80% were exposed for 12 months or longer.
The mean dose of BESREMi was 334 mcg SD ± 121 during the treatment period.
In this pooled safety population, the most common adverse reactions greater than 10%, were liver enzyme elevations (20%), leukopenia (20%), thrombocytopenia (19%), arthralgia (13%), fatigue (12%), myalgia (11%), and influenza-like illness (11%).
The safety findings described below reflect exposure to BESREMi as monotherapy for the treatment of polycythemia vera in 51 patients in the PEGINVERA study [see Clinical Studies (14) ] .
Among the 51 patients receiving BESREMi, 71% were exposed for 12 months or longer, 63% were exposed for three years or longer, and 53% were exposed for greater than five years.
Serious adverse reactions were reported in 16% of patients in the PEGINVERA study.
The most common serious adverse reactions observed during the study (≥ 4%) included urinary tract infection (8%), transient ischemic attack (6%) and depression (4%).
Adverse reactions requiring permanent discontinuation in >2% of patients who received BESREMi included depression (8%), arthralgia (4%), fatigue (4%), and general physical health deterioration (4%) In the PEGINVERA study, patients were not pre-screened for depression or anxiety disorders.
The most common adverse reactions reported in ≥10% of patients in the PEGINVERA study are listed in Table 2.
Table 2 Adverse Reactions in > 10% of Subjects with Polycythemia Vera in the PEGINVERA Study Over 7.5 Years.
Adverse Reactions Adverse Reactions defined as all treatment emergent adverse events BESREMi N=51 % Grouped Term Definitions Influenza-like illness Includes pyrexia, chills, and influenza-like illness.
59 Arthralgia 47 Fatigue Includes asthenia, malaise, and fatigue.
47 Pruritis 45 Nasopharyngitis Includes pharyngitis and nasopharyngitis.
43 Musculoskeletal pain Includes musculoskeletal pain, back pain, pain in extremity, bone pain, flank pain, and spinal pain.
41 Headache Includes headache, migraine, and head pain.
39 Diarrhea 33 Hyperhidrosis Includes night sweats and hyperhidrosis.
29 Nausea 28 Upper respiratory tract infection Includes upper respiratory tract infection, rhinitis, bronchitis, and respiratory tract infection.
27 Local administration site reactions 26 Dizziness 22 Abdominal pain Includes abdominal pain upper, abdominal pain lower, and abdominal pain.
20 Depression 20 Sleep disorder Includes insomnia, sleep disorder, and abnormal dreams.
20 Leukopenia 18 Decreased appetite 18 Alopecia 16 Edema Includes peripheral edema and generalized edema.
16 Hypertension Includes hypertension and hypertensive crisis.
16 Muscle spasms 16 Neutropenia 16 Rash Includes rash, maculopapular rash, and pruritic rash.
16 Transaminase elevations Includes transaminase increase, hepatic enzyme increase, GGT increase, AST increase, and ALT increase.
16 Urinary tract infection 16 Thrombocytopenia 12 Vertigo 12 Clinically relevant adverse reactions in < 10% of patients include: Cardiovascular System: Atrial fibrillation 6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other interferon alfa-2b products may be misleading.
The incidence of binding antibodies to ropeginterferon alfa-2b-njft was 1.4% (2/146) and they were observed as early as 8 weeks post-dosing.
Among the patients who tested positive for binding antibodies, none developed neutralizing antibodies.