Dosing & Uses
Dosage Forms & Strengths
suspension for IV infusion
- 2 x 1013 vector genomes (vg)/mL
- Each vial contains an extractable volume of not less than 8 mL (16 x 1013 vg)
Hemophilia A
Adeno-associated virus vector-based gene therapy indicated for severe hemophilia A (congenital factor VIII deficiency with factor VIII activity <1 IU/dL) in adults without pre-existing antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test
6 x 1013 vector genomes (vg)/kg as a one-time IV infusion
Calculating dose in milliliters (mL) and number of vials required
- Patient dose volume in mL: Body weight in kg x 3 = dose in mL
- Multiplication factor 3 represents the per kg dose (6 x 1013 vg/kg) divided by amount of vg/mL of suspension (2 × 1013 vg/mL)
- Number of vials to be thawed: Patient dose volume (mL) divided by 8 = Number of vials to thaw (round up to next whole vial)
- Division factor 8 represents minimum volume extractable from a vial (8 mL)
Example
- Patient’s weight: 70 kg
- 70 kg x 3 = 210 mL (dose in mL)
- 210 mL/8 = 26.25, which rounds to 27 vials
Dosage Modifications
Renal impairment
- All severities: No dosage adjustment can be recommended
- Safety and effectiveness not established
Hepatic impairment
- All severities: No dosage adjustment can be recommended
- Safety and effectiveness not established
- Clinical studies excluded patients with known hepatic cirrhosis, significant fibrosis (stage 3 or 4 on the Batts-Ludwig scale or equivalent), current hepatitis B or C, or history of hepatic malignancy
Dosing Considerations
Limited information available on safety and effectiveness in patients with HIV infection
Safety and effectiveness in patients with prior or active factor VIII inhibitors not established
Patient selection
-
Perform testing for pre-existing antibodies to AAV5 using FDA-approved companion diagnostic
- Do NOT administer to patients with a positive test for antibodies to AAV5
- Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics
-
Perform factor VIII inhibitor titer testing
- Do NOT administer to patients who are positive for factor VIII inhibitor
Liver testing
- Assess liver function tests (ALT, AST, GGT, ALP, total bilirubin and INR)
- Ultrasound and elastography or laboratory assessments for liver fibrosis
- If there are radiological liver abnormalities and/or liver function test abnormalities (ALT, AST, GGT, ALP or total bilirubin >1.25x ULN or INR ≥1.4), consider consulting a hepatologist to assess eligibility
- Assess ability to receive corticosteroids and/or other immunosuppressive therapy that may be required for an extended period
- Ensure that risks associated with immunosuppression are acceptable for each patient
- Do NOT administer to patients with active acute or uncontrolled chronic infections, known significant hepatic fibrosis (stage 3 or 4 on the Batts-Ludwig scale or equivalent) or cirrhosis, or mannitol hypersensitivity
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (2)
- efavirenz
efavirenz decreases effects of valoctocogene roxaparvovec by pharmacodynamic antagonism. Avoid or Use Alternate Drug. An in vitro study in human primary hepatocytes indicated that efavirenz suppressed factor VIII transcription independent of hepatotoxicity, and expression was not restored upon discontinuation of efavirenz. One HIV positive patient treated with valoctocogene roxaparvovec while on an antiretroviral therapy (ART) regimen consisting of efavirenz, lamivudine, and tenofovir experienced asymptomatic elevations of ALT, AST, and GGT and serum bilirubin at Week 4. The reaction resolved after the ART regimen was changed to a regimen without efavirenz. The patient later reverted to prophylactic use of factor VIII concentrates.
- isotretinoin
isotretinoin decreases effects of valoctocogene roxaparvovec by pharmacodynamic antagonism. Avoid or Use Alternate Drug. An in vitro study in human primary hepatocytes indicated that efavirenz suppressed factor VIII transcription independent of hepatotoxicity, and expression was not restored upon discontinuation of efavirenz. One HIV positive patient treated with valoctocogene roxaparvovec while on an antiretroviral therapy (ART) regimen consisting of efavirenz, lamivudine, and tenofovir experienced asymptomatic elevations of ALT, AST, and GGT and serum bilirubin at Week 4. The reaction resolved after the ART regimen was changed to a regimen without efavirenz. The patient later reverted to prophylactic use of factor VIII concentrates.
Monitor Closely (55)
- allopurinol
allopurinol and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- amiodarone
amiodarone and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- azathioprine
azathioprine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- busulfan
busulfan and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- carbamazepine
carbamazepine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- chlorpromazine
chlorpromazine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- clavulanate
clavulanate and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- dantrolene
dantrolene and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- diclofenac
diclofenac and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- didanosine
didanosine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- dienogest/estradiol valerate
dienogest/estradiol valerate and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- disulfiram
disulfiram and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- drospirenone
drospirenone and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- erythromycin base
erythromycin base and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- erythromycin lactobionate
erythromycin lactobionate and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- erythromycin stearate
erythromycin stearate and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- ethinylestradiol
ethinylestradiol and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- floxuridine
floxuridine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- fluoxymesterone
fluoxymesterone and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- flutamide
flutamide and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- hydralazine
hydralazine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- ibuprofen
ibuprofen and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- ibuprofen IV
ibuprofen IV and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- infliximab
infliximab and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- interferon alfa n3
interferon alfa n3 and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- interferon beta 1a
interferon beta 1a and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- interferon beta 1b
interferon beta 1b and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- isoniazid
isoniazid and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- ketoconazole
ketoconazole and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- levonorgestrel oral
levonorgestrel oral and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
levonorgestrel oral/ethinylestradiol/ferrous bisglycinate and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- mercaptopurine
mercaptopurine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- methotrexate
methotrexate and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- methyldopa
methyldopa and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- minocycline
minocycline and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- nevirapine
nevirapine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- nitrofurantoin
nitrofurantoin and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- norgestrel
norgestrel and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- oxymetholone
oxymetholone and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- peginterferon alfa 2a
peginterferon alfa 2a and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- phenytoin
phenytoin and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- propylthiouracil
propylthiouracil and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- pyrazinamide
pyrazinamide and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- rifampin
rifampin and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- simvastatin
simvastatin and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- sulfadiazine
sulfadiazine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- sulfamethoxazole
sulfamethoxazole and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- sulfasalazine
sulfasalazine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- sulfisoxazole
sulfisoxazole and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- sulindac
sulindac and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- telithromycin
telithromycin and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- thioguanine
thioguanine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- ticlopidine
ticlopidine and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- valproic acid
valproic acid and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
Minor (0)
Adverse Effects
Note: Listed adverse reactions are for all severities unless otherwise indicated
>10%
ALT increases >ULN (81%)
AST increases >ULN (69%)
LDH increases >ULN (57%)
CPK increases >ULN (45%)
Nausea (31%)
Factor VIII activity levels >ULN (28%)
GGT increases >ULN (18%)
Fatigue (16%)
Bilirubin increases >ULN (13%)
1-10%
Headache (7%)
Infusion-related reactions (7%)
Vomiting (6%)
Abdominal pain (6%)
Headache (7%)
Infusion-related reactions (7%)
Vomiting (6%)
Abdominal pain (6%)
Diarrhea (4%)
Dizziness (2%)
Gastroenteritis (1%)
Rash (1%)
Infusion-related reactions, grade ≥3 (1%)
Warnings
Contraindications
Active infections (acute or uncontrolled chronic)
Known significant hepatic fibrosis (stage 3 or 4 on Batts-Ludwig scale), or cirrhosis
Hypersensitivity to mannitol
Cautions
Patients should abstain from alcohol consumption for at least a year following infusion and limit alcohol use thereafter
An increase in factor VIII activity may increase risk for venous and arterial thromboembolic events
Elevated factor VIII activity level above the ULN as measured by the chromogenic substrate assays (CSA), or one-stage clotting assays (OSA), or both assays has occurred
Factor VIII activity above ULN reported following infusion; evaluate for thrombosis risk factors including cardiovascular risk factors before and after use and advise patients accordingly
Monitor for factor VIII activity and factor VIII inhibitors
Malignancy
- Monitor for hepatocellular malignancy in patients with risk factors for hepatocellular carcinoma (eg, hepatitis B or C, non-alcoholic fatty liver disease, chronic alcohol consumption, non-alcoholic steatohepatitis, advanced age) with regular ultrasound (eg, annually) and alpha-fetoprotein testing for 5 years' after administration
- If any malignancy occurs after treatment, contact BioMarin Pharmaceutical Inc. at 1-866-906-6100
Hepatoxicity
- IV administration of a liver-directed AAV vector could lead to liver enzyme elevations (transaminitis), especially ALT elevation
- Transaminitis may occur due to immune-mediated injury of transduced hepatocytes and may reduce the therapeutic efficacy of AAV-vector based gene therapy
- Concomitant medications may cause hepatotoxicity, or decrease factor VIII activity, or change plasma corticosteroid levels which may impact liver enzyme elevation and/or factor VIII activity
- Closely monitor concomitant medication use including herbal products and nutritional supplements, and consider alternative medications in case of potential drug interactions
Infusion-related reaction
- Infusion-related reactions, including hypersensitivity reactions and anaphylaxis, have occurred
- Symptoms include urticaria, pruritus, rash, sneezing, coughing, dyspnea, rhinorrhea, watery eyes, tingling throat, nausea, diarrhea, hypotension, tachycardia, presyncope, pyrexia, rigors, and chills
- Monitor patients during and for at least 3 hr after completing infusion
- Do not infuse faster than 4 mL/min
- If infusion reaction occurs, slow or stop administration
- Restart at a lower rate once infusion reaction has resolved
- Discontinue infusion for anaphylaxis
- Consider management of an infusion reaction with a corticosteroid, antihistamine, and other measures
Drug interaction overview
- Monitor concomitant medications after administering valoctocogene roxaparvovec, and adjust concomitant medications accordingly
- If initiating a new medication, closely monitor ALT and factor VIII activity levels (eg, weekly to every 2 weeks for the first month) to assess potential effects on both levels
-
Isotretinoin
- Not recommend
- Decreased factor VIII activity without ALT elevation was detected in one patient after starting treatment with systemic isotretinoin following valoctocogene roxaparvovec infusion
- Factor VIII activity was 75 IU/dL at Week 60 and transiently decreased to <3 IU/dL at Week 64, after initiating isotretinoin
- After discontinuing isotretinoin at Week 72, factor VIII activity recovered to 46 IU/dL at Week 122
-
Efavirenz
- Not recommended
- HIV-positive patient treated with valoctocogene roxaparvovec while on an antiretroviral therapy regimen consisting of efavirenz, lamivudine, and tenofovir experienced asymptomatic elevations of ALT, AST, and GGT (>5x ULN), and serum bilirubin (>ULN and up to 1.5x ULN) at Week 4
- Reaction resolved after stopping efavirenz
-
Drugs affecting corticosteroid plasma concentration
- Agents that may reduce or increase the plasma concentration of corticosteroids (eg, CYP3A4 inducers or inhibitors) can decrease efficacy of corticosteroids or increase their toxicities
-
Vaccinations
- Do NOT administer live vaccines while on immunosuppressive therapy
- Before infusion, ensure up- to -date vaccinations
- Consider adjusting individual vaccination schedules to accommodate concomitant immunosuppressive therapy
Pregnancy & Lactation
Pregnancy
Not intended for females
There are no data on use in pregnant females to inform a drug-associated risk of adverse developmental outcome
Animal reproduction and developmental toxicity studies not conducted
Unknown whether valoctocogene roxaparvovec can cause fetal harm when administered to pregnant females or can affect reproduction capacity
Contraception for males after administration
- In clinical studies, after administration, transgene DNA was detectable in semen
- In healthy mice, vector DNA detected in testes for at least 182 days after administration at a dose level of 2.1 x 1014 vg/kg
- For 6 months after administration, men of reproductive potential and their female partners must prevent or postpone pregnancy using an effective form of contraception, and men must not donate semen
Lactation
Not intended for females
There is no information regarding drug presence in human milk, effects on breastfed infants, or effects on milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Adeno-associated virus serotype 5 (AAV5)–based gene therapy vector, designed to introduce a functional copy of a transgene encoding the B-domain deleted SQ form of human coagulation factor VIII (hFVIII-SQ)
Transcription of this transgene occurs within the liver, using a liver-specific promoter, resulting in expression of hFVIII-SQ
Expressed hFVIII-SQ replaces missing coagulation factor VIII needed for effective hemostasis
Administration
IV Incompatibilities
Do not use infusion system components other than those described in IV compatibilities
Do not mix or dilute with infusion solutions
Do not infuse in same IV line with any other products
IV Compatibilities
Use 0.9% NaCl to prime and flush the infusion line
Syringes: Polypropylene barrel with a synthetic rubber plunger tip
Syringe cap: Polypropylene
Infusion tubing (tubing extension should not exceed 40 inches): Polyethylene
0.22-micron in-line filter: Polyvinylidene fluoride filter with polyvinyl chloride body
Infusion catheter: Polyurethane-based polymer
Stopcocks: Polycarbonate
18- to 21-gauge sharp needles for extraction from vials: Stainless steel (do not use filter needles to extract from vials)
IV Preparation
General precautions
- Do not expose drug to light of an ultraviolet radiation disinfection lamp
- Prepare using aseptic technique
- Wear gloves and safety glasses during preparation and administration
- Treat spills with a virucidal agent with proven activity against non-enveloped viruses and blot using absorbent materials
- Discard unused product and materials that are exposed to the drug in accordance with the local biosafety guidelines
Thaw and inspect
- Store vials in carton until ready to thaw
- Drug is light sensitive
- Thaw at room temperature; do not thaw or warm vials any other way (thawing time is ~ 2 hr)
- Remove required number of vials from their cartons
- Inspect vials for damage to the vial or cap; discard if damaged
- Set vials upright
- At room temperature, spread vials out evenly or place them in racks for optimal thawing
- Visually confirm all vials have been thawed; there should be no visible ice
- Very gently invert each vial 5x to mix to minimize foaming
- Let suspension settle for ~5 minutes before continuing
- Visually inspect the fully thawed vials; discard if suspension is not clear, not colorless to pale yellow, or contains visible particles
- For microbiological safety, keep thawed suspension in vials until time for infusion
Preparing syringes
- Using 18- to 21-gauge sharp needles, slowly extract drug from vials into infusion-pump syringes
- Number of syringes will depend on dose volume and syringe pump used
- Prepare all infusion-pump syringes before administering
- Contents of multiple vials may be combined into a single syringe
Adding in-line filter and priming
- Insert in-line filter close to infusion site
- Prime tubing and filter
- When replacing filters during infusion, use 0.9% NaCl, for priming and flushing
IV Administration
Do NOT administer as IV push or bolus
Do NOT infuse in the same IV line with any other products
Administer once as a single IV infusion in a setting where personnel and equipment are immediately available to treat infusion-related reactions
Do NOT use a central line or port
Infuse through a suitable peripheral vein, using an infusion catheter with in-line filter and a programmable syringe pump
Infuse at initial rate of 1 mL/min; if tolerated, rate may increase q30min by 1 mL/min and should not exceed 4 mL/min
Infusion time depends on infusion volume, rate, and patient response
After completing infusion, flush infusion line with a sufficient volume of 0.9% NaCl, through the same tubing and filter, and at the same infusion rate
Maintain venous access during subsequent observation period
Infusion-related reactions
- If an infusion-related reaction occurs during administration, decrease infusion rate or stop infusion
- Administer treatment as needed to manage infusion reaction
- If infusion was stopped, restart infusion at a rate of 1 mL/min and consider maintaining at a previously tolerated level for the remaining infusion
- If restarting infusion, complete infusion within 10 hr of initial drug product thaw
- Discontinue infusion for anaphylaxis
Monitoring post-administration
- Monitor AST and CPK as needed to rule out other causes for ALT elevations
- Consider repeating ALT testing within 24-48 hr to confirm ALT elevation before initiating corticosteroid treatment
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Monitoring parameters for ALT
- First 26 weeks: Monitor weekly
- Weeks 26-52 (Year 1): Monitor q1-2 weeks
- Year 2: Monitor q3 months
- After Year 2: Monitor q6 months
- If ALT ≥1.5x baseline or above ULN, consider corticosteroid treatment
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Recommended corticosteroid dosing
- NOTE: Use prednisone or equivalent dose of another corticosteroid
- Starting dose: 60 mg daily for 2 weeks; if ALT continues to increase or does not resolve after 2 weeks, increase corticosteroid dose up to a maximum of 1.2 mg/kg, after ruling out alternative causes for ALT elevation
- Tapering: 40 mg daily for 3 weeks, THEN 30 mg daily for 1 week, THEN 20 mg daily for 1 week, THEN 10 mg daily for 1 week
- Taper corticosteroids after ALT levels reach baseline; individualize taper based on trend of ALT decline, patient’s medical condition, corticosteroid tolerance, and adverse reactions to corticosteroid therapy
- Monitor ALT weekly, and as clinically indicated, during corticosteroid therapy
- Continue to monitor ALT until its return to baseline
- Monitor for and manage adverse reactions secondary to corticosteroid use
- Limited information on benefit of starting a corticosteroid course after first year of valoctocogene roxaparvovec administration
- Consider other immunosuppressive therapies (eg, tacrolimus, mycophenolate mofetil) if corticosteroids are contraindicated, ineffective, or discontinued due to corticosteroid-related reactions
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Monitor factor VIII activity
- Monitor factor VIII activity using same schedule for ALT monitoring
- Consider more frequent monitoring in patients with factor VIII activity levels ≤5 IU/dL and evidence of bleeding, taking into account the stability of factor VIII levels since the previous measurement
- NOTE: It may take several weeks after infusion before drug-derived factor VIII activity rises to a level sufficient for prevention of spontaneous bleeding episodes
- Continued routine prophylaxis support with exogenous factor VIII or other hemostatic products used in managing hemophilia A may be needed during first few weeks after infusion
- Exogenous factor VIII or other hemostatic products may also be needed in case of surgery, invasive procedures, trauma, or bleeds if drug-derived factor VIII activity is deemed insufficient for adequate hemostasis in such situations
- Use of different assays may impact test results; therefore, use same assay and reagents to monitor patients over time, if feasible
- Use of exogenous factor VIII products before and after administering may impede assessment of drug-derived factor VIII activity
- Monitor for factor VIII inhibitors (neutralizing antibodies to factor VIII)
- Test for factor VIII inhibitors especially if bleeding is uncontrolled, or plasma factor VIII activity levels decrease
- Perform regular liver ultrasound (eg, annually) and alpha-fetoprotein (AFP) testing in patients with risk factors of hepatocellular carcinoma (eg, hepatitis B or C, non-alcoholic fatty liver disease, chronic alcohol consumption, non-alcoholic steatohepatitis, advanced age)
Storage
Unopened product
- Transport frozen at ≤ -60ºC (-76ºF)
- Store upright at ≤ -60ºC (-76ºF)
- Store vials in carton until ready to use
- Protect from light
During preparation and thawing
- Thaw at room temperature, up to 25ºC (77ºF)
- Once thawed, do NOT refreeze
- Particles contains no preservative
- If necessary, refrigerate intact vial (stopper not yet punctured) at 2-8ºC (36-46ºF) for up to 3 days, upright
- Store at room temperature, up to 25ºC (77ºF), for up to 10 hr, including hold time in intact vial, preparation time for syringes, and duration of infusion
- Do not expose to the light of an ultraviolet radiation disinfection lamp
- Treat spills with a virucidal agent with proven activity against non-enveloped viruses, and blot using absorbent materials
- Discard unused product and disposable materials that were exposed to drug in accordance with local guidance for pharmaceutical waste
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
