ASH Clinical News July 2017 V2 - Page 36

Novoeight ®
Antihemophilic Factor ( Recombinant )
Rx Only
BRIEF SUMMARY : Please consult package insert for full prescribing information
INDICATIONS AND USAGE : Novoeight ® , Antihemophilic Factor ( Recombinant ), is indicated for use in adults and children with hemophilia A ( congenital factor VIII deficiency or classic hemophilia ) for : Control and prevention of bleeding episodes ; Perioperative management ; Routine prophylaxis to prevent or reduce the frequency of bleeding episodes . Novoeight ® is not indicated for the treatment of von Willebrand disease .
CONTRAINDICATIONS : Novoeight ® is contraindicated in patients who have had life-threatening hypersensitivity reactions , including anaphylaxis , to Novoeight ® or its components ( including traces of hamster proteins ).
WARNINGS AND PRECAUTIONS : Hypersensitivity Reactions : Hypersensitivity reactions , including anaphylaxis , are possible with Novoeight ® . Novoeight ® contains trace amounts of hamster proteins . Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins . Early signs of hypersensitivity reactions that can progress to anaphylaxis include angioedema , chest tightness , dyspnea , wheezing , urticaria , and pruritus . Immediately discontinue administration and initiate appropriate treatment if allergicor anaphylactic-type reactions occur . Neutralizing Antibodies : Formation of neutralizing antibodies ( inhibitors ) to factor VIII can occur following administration of Novoeight ® . Monitor all patients for the development of inhibitors by appropriate clinical observation and laboratory testing . If the expected plasma levels of factor VIII activity are not attained , or if bleeding is not controlled with an appropriate dose , perform testing for factor VIII inhibitors . Monitoring Laboratory Tests : Monitor plasma factor VIII activity levels by the one-stage clotting assay or the chromogenic substrate assay to confirm that adequate factor VIII levels have been achieved and maintained , when clinically indicated . Perform assay to determine if factor VIII inhibitor is present if expected plasma factor VIII activity levels are not attained , or if bleeding is not controlled with the expected dose of Novoeight ® . Determine inhibitor levels in Bethesda Units .
ADVERSE REACTIONS : The most frequently reported adverse reactions ( ≥ 0.5 %) were injection site reactions , increased hepatic enzymes , and pyrexia . 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 clinical trials of another drug and may not reflect the rates observed in clinical practice . During the clinical development of Novoeight ® , 214 male previously treated patients ( PTPs ; exposed to a factor VIII-containing product for ≥150 days ) with severe hemophilia A ( factor VIII level ≤1 %) received at least one dose of Novoeight ® as part of either routine prophylaxis , on-demand treatment of bleeding episodes , perioperative management of major and minor surgical , dental , or other invasive procedures , or pharmacokinetic evaluation of Novoeight ® . Thirty-one subjects ( 14 %) were < 6 years of age , 32 ( 15 %) were 6 to < 12 years of age , 16 ( 7 %) were adolescents ( 12 to < 16 years of age ), and 135 ( 63 %) were adults ( 16 years of age and older ). The subjects received a total of 33,272 injections with a median of 127 injections of Novoeight ® ( range 1-442 ) per subject , and had a total of 32,929 exposure days during prevention and treatment of bleeds . The most frequently reported adverse reactions in previously treated patients was injection site reactions ( 2.3 %), increased hepatic enzymes ( 1.4 %), and pyrexia ( 0.9 %). Immunogenicity : Subjects were monitored for neutralizing antibodies to factor VIII and binding antibodies to CHO and murine protein . No subjects developed confirmed neutralizing antibodies to factor VIII . One twenty-two month old child had a positive neutralizing antibody to factor VIII of 1.3 [ BU ] in the Bethesda assay after 15 exposure days that was not confirmed when checked after 20 exposure days . In vivo recovery was normal for this child and no clinical adverse findings were observed . No patients developed de novo anti-murine antibodies . Nineteen subjects were positive for anti-Chinese hamster ovary ( CHO ) cell protein antibodies . Two of these subjects changed from anti-CHO negative to anti-CHO positive and 6 subjects changed from anti-CHO positive to anti-CHO negative . The remaining 11 subjects were either positive throughout the trials ( n = 6 ), negative at baseline and end-of trial but with transient positive samples ( n = 2 ), or positive at baseline and end-of trial but with negative samples in between ( n = 3 ). No clinical adverse findings were observed in any of these subjects . 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 .
USE IN SPECIFIC POPULATIONS : Pregnancy : Risk Summary : As hemophilia mainly affects males , there are no adequate and wellcontrolled studies using Novoeight ® in pregnant women to determine whether there is a drug-associated risk . Animal reproduction studies have not been conducted with Novoeight ® . In the U . S . general population , the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4 % and 15-20 %, respectively . There is no reliable data on the incidences specific to the hemophilia A population . Lactation : Risk Summary : There is no information regarding the presence of Novoeight ® in human milk , the effect on the breastfed infant , and the effects on milk production . The developmental and health benefits of breastfeeding should be considered along with the mother ’ s clinical need for Novoeight ® and any potential adverse effects on the breastfed infant from Novoeight ® or from the underlying maternal condition . Pediatric Use : Children have shorter half-life and lower recovery of factor VIII than adults . Because clearance ( based on per kg body weight ) has been demonstrated to be higher in the pediatric population , higher or more frequent dosing based on body weight may be needed . Safety and efficacy studies have been performed in 79 previously treated pediatric patients < 16 years of age . Thirty-one of these subjects ( 39 %) were < 6 years of age , 32 ( 41 %) were 6 to < 12 years of age , and 16 ( 20 %) were adolescents ( 12 to < 16 years of age ). All subjects received preventive treatment every other day or three times weekly . A total of 244 bleeds in 54 subjects were treated with Novoeight ® . The majority of the bleeds ( 91 %) were of mild / moderate severity , 41 % of the bleeds were spontaneous and 58 % of the bleeds were localized in joints . Of these 244 bleeds , 210 ( 86 %) were rated excellent or good in their response to treatment with Novoeight ® and 3 ( 1.2 %) were rated as having no response . A total of 222 ( 91 %) of the bleeds were resolved with one or two injections of Novoeight ® . Routine prophylactic treatment has been shown to reduce joint bleeding . Geriatric Use : Clinical studies of Novoeight ® did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients .
More detailed information is available upon request .
Version : 5
For information contact : Novo Nordisk Inc . 800 Scudders Mill Road Plainsboro , NJ 08536 , USA 1-844-30-EIGHT
Manufactured by : Novo Nordisk A / S Novo Allé , DK-2880 Bagsvaerd
Novoeight ® is a registered trademark of Novo Nordisk Health Care AG .
Patent Information : http :// novonordisk-us . com / patients / products / productpatents . html
© 2016 Novo Nordisk USA16HDM05035 12 / 2016
Novoeight ® Antihemophilic Factor (Recombinant) Rx Only BRIEF SUMMARY: Please consult package insert for full prescribing information INDICATIONS AND USAGE: Novoeight ® , Antihemophilic Factor (Recombinant), is indicated for use in adults and children with hemophilia A (congenital factor VIII deficiency or classic hemophilia) for: Control and prevention of bleeding episodes; Perioperative management; Routine prophylaxis to prevent or reduce the frequency of bleeding episodes. Novoeight ® is not indicated for the treatment of von Willebrand disease. CONTRAINDICATIONS: Novoeight ® is contraindicated in patients who have had life-threatening hypersensitivity reactions, including anaphylaxis, to Novoeight ® or its components (including traces of hamster proteins). WARNINGS AND PRECAUTIONS: Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis, are possible with Novoeight ® . Novoeight ® contains trace amounts of hamster proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins. Early signs of hypersensitivity reactions that can progress to anaphylaxis include angioedema, chest tightness, dyspnea, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if allergic- or anaphylactic-type reactions occur. Neutralizing Antibodies: Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of Novoeight ® . Monitor all patients for the development of inhibitors by appropriate clinical observation and laboratory testing. If the expected plasma levels of factor VIII activity are not attained, or if bleeding is not controlled with an appropriate dose, perform testing for factor VIII inhibitors. Monitoring Laboratory Tests: Monitor plasma factor VIII activity levels by the one-stage clotting assay or the chromogenic substrate assay to confirm that adequate factor VIII levels have been achieved and maintained, when clinically indicated. Perform assay to determine if factor VIII inhibitor is present if expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with the expected dose of Novoeight ® . Determine inhibitor levels in Bethesda Units. ADVERSE REACTIONS: The most frequently reported adverse reactions (≥ 0.5%) were injection site reactions, increased hepatic enzymes, and pyrexia. 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 clinical trials of another drug and may not reflect the rates observed in clinical practice. During the clinical development of Novoeight ® , 214 male previously treated patients (PTPs; exposed to a factor VIII-containing product for ≥150 days) with severe hemophilia A (factor VIII level ≤1%) received at least one dose of Novoeight ® as part of either routine prophylaxis, on-demand treatment of bleeding episodes, perioperative management of major and minor surgical, dental, or other invasive procedures, or pharmacokinetic evaluation of Novoeight ® . Thirty-one subjects (14%) were <6 years of age, 32 (15%) were 6 to <12 years of age, 16 (7%) were adolescents (12 to <16 years of age), and 135 (63%) were adults (16 years of age and older). The subjects received a total of 33,272 injections with a median of 127 injections of Novoeight ® (range 1-442) per subject, and had a total of 32,929 exposure days during prevention and treatment of bleeds. The most frequently reported adverse reactions in previously treated patients was injection site reactions (2.3%), increased hepatic enzymes (1.4%), and pyrexia (0.9%). Immunogenicity: Subjects were monitored for neutralizing antibodies to factor VIII and binding antibodies to CHO and murine protein. No subjects developed confirmed neutralizing antibodies to factor VIII. One twenty-two month old child had a positive neutralizing antibody to factor VIII of 1.3 [BU] in the Bethesda assay after 15 exposure days that was not confirmed when checked after 20 exposure days. In vivo recovery was normal for this child and no clinical adverse findings were observed. No patients developed de novo anti-murine antibodies. Nineteen subjects were positive for anti-Chinese hamster ovary (CHO) cell protein antibodies. Two of these subjects changed from anti-CHO negative to anti-CHO positive and 6 subjects changed from anti-CHO positive to anti-CHO negative. The remaining 11 subjects were either positive throughout the trials (n=6), negative at baseline and end-of trial but with transient positive samples (n=2), or positive at baseline and end-of trial but with negative samples in betwe V26Ɩ6GfW'6RfFw2vW&P'6W'fVBbFW6R7V&V7G2FRFWFV7FbF&Gf&Fগ2vǒFWVFVBFR6V6FfGB7V6f6GbFR76FFFǒFR'6W'fVB6FV6RbF&G6VFrWWG&ƗpF&G6FfG76&RfVV6VB'6WfW&f7F'26VFr76WFFw6RFƖrF֖rb6P6V7F66֗FBVF6F2BVFW&ǖrF6V6RU4R5T4d2TD3&Vv7&67V'2VƖǒffV7G2W2FW&R&RFWVFRBvVЦ6G&VB7GVFW2W6rfVvB *&VvBvVFFWFW&֖PvWFW"FW&R2G'Vr766FVB&6&W&GV7F7GVFW0fRB&VV6GV7FVBvFfVvB *FRR2vVW&VFFRW7FFVB&6w&VB&6b"&'FFVfV7B@֗66'&vR6Ɩ6ǒ&V6v旦VB&Vv6W22"BRBR#R&W7V7FfVǒFW&R2&VƖ&RFFFR6FV6W27V6f2FFRVƖVF7FF&67V'FW&R2f&F&Vv&FrFR&W6V6RbfVvB *V֖ƲFPVffV7BFR'&V7FfVBfBBFRVffV7G2֖Ʋ&GV7FFRFWfVVFBVF&VVfG2b'&V7FfVVFr6VB&P66FW&VBrvFFRFW.( 26Ɩ6VVBf"fVvB *@FVFGfW'6RVffV7G2FR'&V7FfVBfBg&fVvB * g&FRVFW&ǖrFW&6FFVFG&2W6S6G&VfP6'FW"bƖfRBvW"&V6fW'bf7F"dFGVG2&V6W6P6V&6R&6VBW"r&GvVvB2&VVFV7G&FVBF&RvW"FRVFG&2VFvW""&Rg&WVVBF6p&6VB&GvVvB&RVVFVB6fWGBVff677GVFW0fR&VVW&f&VBs&WfW6ǒG&VFVBVFG&2FVG2`V'2bvRF'GRbFW6R7V&V7G23RvW&RbV'2bvR3"CRvW&RbF"V'2bvRBb#RvW&RFW66VG2 FbV'2bvR7V&V7G2&V6VfVB&WfVFfRG&VFVBWfW'FW"F"F&VRFW2vVVǒFFb#CB&VVG2SB7V&V7G0vW&RG&VFVBvFfVvB *FR&GbFR&VVG2RvW&Pb֖BFW&FR6WfW&GCRbFR&VVG2vW&R7FVW2@SRbFR&VVG2vW&R6ƗVBG2bFW6R#CB&VVG2#bRvW&R&FVBW6VVB"vBFV"&W76RFG&VFVBvFfVvB *B2"RvW&R&FVB2fr&W76RFF`##"RbFR&VVG2vW&R&W6fVBvFR"GvV7F2`fVvB *&WFR&7F2G&VFVB2&VV6vF&VGV6PB&VVFrvW&G&2W6S6Ɩ67GVFW2bfVvB *FB@6VFR7Vff6VBV&W'2bFVG2vVBcRBfW"FFWFW&֖PvWFW"FW&W7BFffW&VFǒg&VvW"FVG2&RFWFVBf&F2f&RW&WVW7BfW'6Pf"f&F6F7Cf&F62ࣃ67VFFW'2֖&@6&&S3bU4ӃCB3Tt@Vf7GW&VB'f&F60f:D#&w7fW&@fVvB *2&Vv7FW&VBG&FV&bf&F6VF6&RrFVBf&FGGf&F6W26FVG2&GV7G2&GV7BЧFVG2F*#bf&F6U4dDS3R"#