Onasemnogene abeparvovec
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: SERIOUS LIVER INJURY Acute serious liver injury and elevated aminotransferases can occur with ITVISMA. [see Warnings and Precautions (5.1)] Patients with preexisting liver impairment may be at higher risk. [see Warnings and Precautions (5.1)] Prior to intrathecal injection, assess liver function by clinical examination and laboratory testing. Administer systemic corticosteroid before and after ITVISMA injection. Continue to monitor liver function for at least 3 months after injection, and at other times as clinically indicated. [see Dosage and Administration (2.1, 2.4)]. WARNING: SERIOUS LIVER INJURY See full prescribing information for complete boxed warning.
Acute serious liver injury and elevated aminotransferases can occur with ITVISMA. ( 5.1 ) Patients with preexisting liver impairment may be at higher risk. ( 5.1 ) Prior to intrathecal injection, assess liver function by clinical examination and laboratory testing. Administer systemic corticosteroid before and after ITVISMA injection. Continue to monitor liver function for at least 3 months after injection, and at other times as clinically indicated. ( 2.1 , 2.4 )
Dosing in kidney impairment
TMA is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. Concurrent immune system activation (e.g., infections, vaccinations) may be a contributing factor. Prompt attention to signs and symptoms of TMA is advised, as TMA can result in life-threatening or fatal outcomes. Monitor platelet counts on a regular basis following ITVISMA injection [see Warnings and Precautions] , as well as signs and symptoms of TMA, such as hypertension, bruising easily, seizures, or decreased urine output.
In case these signs and symptoms occur in the presence of thrombocytopenia, further diagnostic evaluation for hemolytic anemia and renal dysfunction should be promptly undertaken. If clinical signs, symptoms and/or laboratory findings consistent with TMA occur, consult a hematologist and/or nephrologist immediately to manage TMA as clinically indicated. 5.5 Elevated Cardiac Troponin I Increases in cardiac troponin I levels have occurred following ITVISMA administration without clinical sequelae [see Adverse Reactions] .
Dosing in liver impairment
Hepatic Impairment Patients with preexisting hepatic impairment or acute hepatic viral infection may be at higher risk of liver injury. ITVISMA therapy should be carefully considered in patients with liver impairment [see Warnings and Precautions] .
Preparation and administration
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Preparation Required supplies and materials (not supplied) Needle for withdrawal Syringe Syringe cap Spinal needle The supplies and materials compatible with ITVISMA are listed in Table 2. Device components must be indicated for intrathecal or neuraxial use. Ensure all device components use the same connector type. Incompatible device connections may result in dose loss during administration. [See table below.] 5mL to 10mL Syringe a Polypropylene Syringe cap a Polypropylene or Polyethylene or Methacrylate-Acrylonitrile-Butadiene-Styrene 22G to 27G Spinal needle, maximum 150mm long Stainless steel Vial Preparation: ITVISMA should be prepared aseptically.
Thaw ITVISMA in the refrigerator for approximately 4 hours, or at room temperature for approximately 1 hour. If thawed in the refrigerator, remove ITVISMA from refrigerator on day of dosing. Do not use ITVISMA unless thawed. Prior to intrathecal injection, ITVISMA should be brought to room temperature. When thawed, ITVISMA is a clear to slightly opaque, colorless to faint white liquid, free of particles.
After withdrawal of ITVISMA from the vial, a visual inspection is required. DO NOT use if particulates, cloudiness, or discoloration are visible. DO NOT SHAKE. Immediately prior to dosing, draw the content from the vial into the syringe, remove air from syringe, confirm the dose volume of 3 mL in the syringe, cap syringe and deliver to patient injection location.
Once dose is drawn into the syringe, it may be held in the refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours, including a 5-hour maximum time out-of-refrigeration allowance within the 24-hour period. Discard the vector-containing syringe if not injected within this time period. DO NOT REFREEZE. Procedural Preparation Instructions: Consider sedation if indicated by the patient’s clinical status.
Consider imaging techniques to guide intrathecal injection of ITVISMA. Evaluate patient prior to and after intrathecal injection for conditions that may contraindicate lumbar puncture or increase procedural risk to prevent serious complications.
Administration Intrathecal Injection Instructions: Prior to administration, remove 3 mL of cerebrospinal fluid (CSF) using a lumbar puncture needle to create space for injection volume. Administer ITVISMA as an intrathecal bolus injection over approximately 1 to 2 minutes through the lumbar puncture needle. Place patient in Trendelenburg position (head down at 30 degrees for 15 minutes).
Adjust patient positioning and duration based on the patient’s clinical status to enhance distribution. Follow standard post-lumbar puncture care protocols. Monitoring Following ITVISMA Injection: Liver function (AST, ALT, total bilirubin) weekly for the month after ITVISMA injection and during the corticosteroid taper period (over the next 28 days or longer if needed).
If the patient is clinically stable with unremarkable findings (normal clinical exam, total bilirubin, and ALT and AST levels below 2 × ULN) at the end of the corticosteroid taper period, continue to monitor liver function every other week for another month [see Warnings and Precautions] . Platelet counts weekly for the first month and as clinically indicated until platelet counts return to baseline [see Warnings and Precautions] .
Drug interactions
Check onasemnogene abeparvovec against a medication listLabel text (1 paragraph)
Adjust patient’s vaccination schedule to accommodate concomitant corticosteroid administration prior to and following ITVISMA injection [see Dosage and Administration (2.1)] . Certain vaccines, such as measles, mumps, and rubella (MMR) and varicella, are contraindicated for patients on a substantially immunosuppressive steroid dose (i.e., ≥ 2 weeks of daily receipt of 20 mg or 2 mg/kg body weight of prednisone or equivalent). Adjust patient’s vaccination schedule to accommodate concomitant corticosteroid administration prior to and following ITVISMA injection. ( 7 )
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
DLikelihood score D: Possible cause of clinically apparent liver injury.
Onasemnogene abeparvovec is a unique gene therapy agent used to correct the abnormal gene responsible for spinal muscular atrophy type 1, a rare progressive neuromuscular disorder that typically leads to disability and death within the first two years of life. Onasemnogene abeparvovec is given as a one-time intravenous infusion and has been linked to serum aminotransferase elevations which can be associated with jaundice and severe acute liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary There are no clinical studies in pregnant women to inform a product-associated risk. Animal reproduction studies in mice have shown no risk of fetal abnormalities nor transfer to mouse fetus with intravenous (IV) administration of onasemnogene abeparvovec on gestational day 6 at dose levels equivalent to at least 7 times the clinical intrathecal dose. It is not known whether ITVISMA has the potential to be transferred to the fetus in humans. Therefore, women who are pregnant or may become pregnant should only be treated with ITVISMA after a thorough benefit-risk evaluation.
In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study in mice, pregnant animals received an IV dose of either 1.1 x 10 13 vg/kg or 1.1 x 10 14 vg/kg of onasemnogene abeparvovec on gestational day 6, which resulted in no evidence of maternal toxicity, embryo-fetal toxicity, teratogenicity, or reduced viability. Onasemnogene abeparvovec DNA was detected in the placenta at low levels but was not detected in any fetal tissue on gestational day 18.
The no observed adverse effect level for maternal and developmental toxicity is 1.1 x 10 14 vg/kg, corresponding to at least 7 times the recommended clinical IT dose level based on body weight.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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