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ITVISMA onasemnogene abeparvovec-brve 40000000000000 [arb'U]/mL Injection, Suspension — NDC 71894-0200-02 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

ITVISMA onasemnogene abeparvovec-brve 40000000000000 [arb'U]/mL Injection, Suspension — NDC 71894-200-02 (Billing 71894-0200-02)

by Novartis Innovative Technologies Inc. · 1 VIAL, SINGLE-DOSE in 1 CARTON / 3 mL in 1 VIAL, SINGLE-DOSE

This is a package of ITVISMA onasemnogene abeparvovec-brve 40000000000000 [arb'U]/mL Injection, Suspension from Novartis Innovative Technologies Inc., marketed since Nov 2025 and currently FDA-listed. It is this product's only package size.

NDC 71894-0200-02
🏷️ FDA NDC (as labeled) 71894-200-02 billing pads the product segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 71894-200-02 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
71894 labeler · 200 product · 02 package
Package marketed since
Nov 24, 2025
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Barcode (UPC-A, from the NDC)
3 7189420002 0
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 71894-200-02
Product NDC 71894-200
11-digit billing NDC 71894020002
NCPDP billing unit EA — each (per item)
RxCUI 2727307, 2727314
UNII MLU3LU3EVV
Application # BLA125856
SPL Set ID ab2e1c6c-4f95-4243-9296-1734e0a30591
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2025-11-24
Route INTRATHECAL
Dosage form INJECTION, SUSPENSION
Substance ONASEMNOGENE ABEPARVOVEC
Biologic (Purple Book) 351(a)

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 088447
GCN 58577
HICL code 051022
Ingredient (HICL) Onasemnogene Abeparvovec-Brve
HIC1 code Z
Therapeutic class — broad (HIC1) Body As A Whole
HIC2 code Z0
Therapeutic class — intermediate (HIC2) Biologicals (Continued 1)
HIC3 code Z0K
Therapeutic class — specific (HIC3) Gene Therapy Agents - Smn Protein Deficiency
AHFS code 26:12.00.00
AHFS class Gene Therapy
FDB label name ITVISMA VIAL
FDB brand name Itvisma
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 088447
  • GCN: 58577
  • HICL (First Databank): 051022
  • AHFS class code: 26:12.00.00
  • RxCUI (RxNorm): 2727307
Why two NDCs? The FDA registers this code as 71894-200-02 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 71894-0200-02. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Other drugs for disorders of the musculo-skeletal system class.

Drug family (ATC) Other drugs for disorders of the musculo-skeletal system
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name ITVISMA VIAL Ingredient Onasemnogene Abeparvovec-Brve
📖 What it is MedlinePlus · NLM

Onasemnogene abeparvovec-xioi injection is used to treat spinal muscular atrophy (an inherited condition that reduces muscle strength and movement) in certain infants and children less than 2 years old. Onasemnogene abeparvovec-xioi is in a class of medications called gene therapy. It works by replacing a defective gene which helps preserve muscle and nerve function.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Zolgensma delivers a working copy of the gene your child was born without — the SMN1 gene — directly into their cells using a specially designed viral carrier. Without this gene, t...
  • What exactly does Zolgensma do for my child?
  • Yes, Zolgensma is given just once. The therapy is designed to deliver a lasting copy of the needed gene. Giving it a second time has not been studied, and it isn't recommended — in...
  • Is this really a one-time treatment? Will my child ever need it again?
📖 Read our full Onasemnogene Abeparvovec-Xioi guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
71894-0200-02 You're viewing this Main listing 1 VIAL, SINGLE-DOSE in 1 CARTON / 3 mL in 1 VIAL, SINGLE-DOSE 2025-11-24 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Itvisma 40000000000000 [arb'U]/mLthis 71894-0200-02 Novartis 1 vial — — FDA listed —
About this product: this is a biologic. Biologics don't have small-molecule generics — competition comes from FDA-licensed biosimilars (shown above), not generics.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & biosimilar status

🏛️
2025
First FDA approval
Nov 2025
📍
2026
Currently FDA-listed
1 year listed
🛡️
2037
Latest patent/protection listed
not a guaranteed launch date
🧬Biologic — competition comes from biosimilars

Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Nov 2037. This may affect when biosimilars become widely available, but it is not a guaranteed launch date.
📅 FDA approved Nov 24, 2025 ⏳ ~11.1 yr to latest listed protection

Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.

FDA Purple Book — biosimilars & interchangeables ⓘ
Reference product
Itvismaonasemnogene abeparvovec-brve Zolgensmaonasemnogene abeparvovec-xioi
🔒 No FDA-licensed biosimilars or interchangeable biosimilars are listed yet for this biologic. It currently has no biosimilar competition in the FDA Purple Book.
Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.
Patents & exclusivity — FDA Purple Book
Exclusivity RefProduct
2025 2027 2029 2031 2033 2035 2037
Today
LOE
Biologic patent Exclusivity
🏛️Reference-product exclusivity
A flat 12 years of FDA market protection from first licensure. No biosimilar can be licensed before it ends — regardless of patents.
🧪Listed biologic patents
Patents the reference maker lists covering the molecule, formulation, or manufacturing. A biosimilar generally can’t launch until these resolve.
🔁Interchangeability
An interchangeable biosimilar may be substituted at the pharmacy (state laws vary). The first one can earn its own exclusivity period.
🛈 What do these terms mean?
Biologic patent
A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
Reference-product exclusivity
A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
Interchangeable exclusivity
The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
Earliest biosimilar (LOE)
The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.

Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.

FDA exclusivity
CodeWhat it grantsExpires
RefProductReference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this dateNov 24, 2037
Common questions
Is there a biosimilar for ITVISMA VIAL?
No FDA-licensed biosimilar is currently listed for this biologic in the FDA Purple Book.
Why do different websites show different biosimilar dates?
Biosimilar availability isn’t based on one single date. Some sources use the reference-product exclusivity, some use the last listed patent, and patent litigation, settlements, and licenses can all change the real-world launch date. This page shows the underlying Purple Book dates so you can see why estimates differ.
Can a biosimilar launch before the last patent expires?
Sometimes. A biosimilar maker may settle with the reference manufacturer or receive a license to launch earlier. In other cases, the last listed protection delays competition.
What does “current Purple Book estimate” mean?
It means we’re using the latest patent and exclusivity dates currently listed in the FDA Purple Book. It is not a guaranteed launch date.
What does “FDA listed” mean?
It means the product appears in the FDA’s official directory. That’s a good sign a product exists for the U.S. market, but on its own it does not confirm a pharmacy can get it today. Where we have recent retail pricing data, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Purple Book for a patent or exclusivity on the reference biologic. It can affect when a biosimilar becomes widely available — but it is not a guaranteed launch date. Settlements and licenses can move the real date earlier or later.
Built from the FDA Purple Book Patent List (patents the reference-product sponsor has publicly listed under the BPCIA) plus reference-product exclusivity. Biosimilars cannot launch until these clear; patent litigation and settlements can shift the real date. Biologics have no small-molecule generics — competition comes from FDA-licensed biosimilars, not the Orange Book.
Where does this data come from?
Patents and exclusivity from the FDA Purple Book (biologics), refreshed from public FDA data. Biosimilar launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 02F3473H9O
    A mineral salt used in medications as a source of magnesium. It helps bind ingredients together, improve texture, and maintain the product's stability during storage.
  • UNII LQA7B6G8JG
    A synthetic polymer made by combining water-soluble compounds. It acts as a surfactant and solubilizer to help mix oil and water-based ingredients, improving the medicine's texture and how active ingredients dissolve.
  • UNII 451W47IQ8X
    Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
  • UNII 023C2WHX2V
    Tromethamine is a chemical buffer that helps maintain the proper acidity level in liquid medicines. It neutralizes acids and stabilizes the solution so the medication remains effective and safe throughout its shelf life.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

5 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerNovartis Innovative Technologies Inc.
FDA applicationBLA125856 (BLA)
Labeler code71894
First marketedNov 2025
Product typeHuman Prescription Drug
Portfolio38 products on file

More NDCs from Novartis Innovative Technologies Inc. labeler code 71894

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 165 words ▾

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 )

🎯 Indications and Usage 74 words ▾

1 INDICATIONS AND USAGE ITVISMA is indicated for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients 2 years of age and older with confirmed mutation in survival motor neuron 1 (SMN1) gene. ITVISMA is an adeno-associated virus (AAV) vector-based gene therapy indicated for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients 2 years of age and older with confirmed mutation in SMN1 gene. ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION For single-dose intrathecal injection only. ( 2 ) The recommended dose of ITVISMA is 1.2 × 10 14 vector genomes (vg). ( 2.2 ) Administer ITVISMA as an intrathecal bolus injection over approximately 1 to 2 minutes.

( 2.4 ) Postpone ITVISMA in patients with infections until the infection has resolved and the patient is clinically stable. ( 2.1 ) Starting one day prior to ITVISMA injection, administer systemic corticosteroids equivalent to oral prednisolone at 1 mg/kg of body weight per day for a total of 30 days. At the end of the 30-day period, check liver function by clinical examination and by laboratory testing.

For patients with unremarkable findings, taper the corticosteroid dose gradually over the next 28 days. If liver function abnormalities persist, continue systemic corticosteroids (equivalent to oral prednisolone at 1 mg/kg/day) until findings become unremarkable, and then taper the corticosteroid dose gradually over the next 28 days or longer if needed. Do not stop systemic corticosteroids abruptly.

( 2.2 ) If at any time patients do not respond adequately to the equivalent of 1 mg/kg/day oral prednisolone, based on the patient’s clinical course, prompt consultation with a gastroenterologist or hepatologist and adjustment to the recommended corticosteroid regimen may be considered. ( 2.2 )

2.1Critical Dosing Information For single-dose intrathecal injection only. Patients previously treated with ZOLGENSMA (onasemnogene abeparvovec-xioi) should not be treated with ITVISMA [see Clinical Pharmacology (12.1)] . ITVISMA should only be administered intrathecally using a lumbar puncture by healthcare professionals (e.g., interventional radiologist or neurologist) experienced in performing lumbar punctures.

Prior to ITVISMA injection: Due to the increased risk of serious systemic immune response, administer ITVISMA to patients who are clinically stable in their overall baseline health status (e.g., hydration and nutritional status, absence of infection, respiratory status) prior to administration. Postpone ITVISMA in patients with active or recent infections, until the infection has resolved, and the patient is clinically stable. Clinical signs or symptoms of infection should not be evident at the time of ITVISMA injection.

Assess vaccination status. Vaccination status should be up-to-date prior to ITVISMA administration. Recommend seasonal prophylaxis against respiratory syncytial virus (RSV).

Assess liver function (clinical examination and laboratory testing including aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, prothrombin time, partial thromboplastin time (PTT), international normalized ratio (INR), and total bilirubin) [see Warnings and Precautions (5.1), Use in Specific Populations (8.6)] . Obtain creatinine and complete blood count (including hemoglobin and platelet count) [see Warnings and Precautions (5.2, 5.4)] . Perform baseline testing for the presence of anti-AAV9 antibodies.

One day prior to ITVISMA injection, begin administration of systemic corticosteroids equivalent to oral prednisolone at 1 mg per kg of body weight per day (mg/kg/day) for a total of 30 days. Do not stop systemic corticosteroids abruptly. After the 30-day period, taper prednisolone (or equivalent) as needed according to the clinical status and liver function testing [see Warnings and Precautions (5.1, 5.2)] .

See Table 1 for the recommended corticosteroid regimen. Do not re-administer ITVISMA.

2.2Dose The recommended dose of ITVISMA is 1.2 × 10 14 vector genomes (vg). Table 1 includes the recommended corticosteroid regimen prior to and following ITVISMA injection. If at any time patients do not respond adequately to the equivalent of 1 mg/kg/day oral prednisolone, based on the patient’s clinical course, obtain prompt consultation with a gastroenterologist or hepatologist and consider adjustment to the recommended corticosteroid regimen, including increased dose, longer duration or p… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 105 words ▾

3 DOSAGE FORMS AND STRENGTHS ITVISMA is a clear to slightly opaque, colorless to faint white suspension for intrathecal injection. Each single-dose vial contains 1.2 × 10 14 vg of onasemnogene abeparvovec in 3 mL of suspension. ITVISMA has a nominal concentration of 4 × 10 13 vg/mL, and each vial contains an extractable volume of not less than 3 mL.

Each single-dose vial contains 1.2 × 10 14 vg of onasemnogene abeparvovec in 3 mL of suspension. ITVISMA has a nominal concentration of 4 × 10 13 vg/mL, and each vial contains an extractable volume of not less than 3 mL. ( 3 )

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Hepatotoxicity: Prior to ITVISMA injection, assess liver function of patients by clinical examination and laboratory testing. Continue to monitor liver function for at least 3 months after injection, and at other times as clinically indicated. ( 2.1 , 2.4 , 5.1 ) Thrombocytopenia: Monitor platelet counts before ITVISMA injection, and at least weekly for the first month and as clinically indicated until platelet counts return to baseline.

( 2.1 , 2.4 , 5.2 ) Peripheral Sensory Neuropathy: Consider complete neurologic evaluation and other testing and/or symptom management based on the patient's clinical presentation. ( 5.3 ) Thrombotic Microangiopathy (TMA): Prompt attention to signs and symptoms of TMA is advised, as TMA can result in life-threatening or fatal outcomes. If clinical signs, symptoms and/or laboratory findings occur, consult a hematologist and/or nephrologist immediately to manage as clinically indicated.

( 5.4 ) Elevated Cardiac Troponin I: Increases in cardiac troponin I have occurred following ITVISMA injection. Consider cardiac evaluation after ITVISMA administration and consult a cardiologist as needed. ( 5.5 ) AAV Vector Integration and Risk of Tumorigenicity: There is a theoretical risk of tumorigenicity due to integration of AAV vector DNA into the genome.

Report cases of tumors in patients who received ITVISMA, to Novartis Gene Therapies, Inc. ( 5.6 )

5.1Hepatotoxicity Hepatotoxicity, with elevated ALT and/or AST levels, has occurred with ITVISMA [see Adverse Reactions (6.1)] . Patients with preexisting hepatic impairment or acute hepatic viral infection may be at higher risk of liver injury. In order to mitigate potential aminotransferase elevations, administer systemic corticosteroid before and after ITVISMA injection.

Immune-mediated hepatotoxicity may require adjustment of the corticosteroid treatment regimen, including longer duration, increased dose, or prolongation of the corticosteroid taper [see Dosage and Administration (2.2)] . Prior to ITVISMA injection, assess liver function by clinical examination and laboratory testing. Continue to monitor liver function for at least 3 months after ITVISMA administration, and at other times as clinically indicated.

Monitor AST, ALT and total bilirubin weekly for the month after ITVISMA administration and during the corticosteroid taper period. If the patient is clinically stable with unremarkable findings at the end of the corticosteroid taper period, continue to monitor liver function every other week for another month. Tapering of systemic corticosteroids should not be considered until AST/ALT levels are less than 2 × ULN [see Dosage and Administration (2.1, 2.4)] .

Monitor patients with worsening liver function test results and/or signs or symptoms of acute illness (e.g., vomiting, deterioration in health). In case hepatic injury is suspected, further testing is recommended (e.g., albumin, prothrombin time, partial thromboplastin time (PTT) and international normalized ratio (INR)). Promptly consult with a gastroenterologist or hepatologist, as necessary.

5.2Thrombocytopenia Transient decreases in platelet counts were observed within the first week after ITVISMA administration [see Adverse Reactions (6.1)] . The platelets counts are expected to return to baseline two weeks following ITVISMA injection. Monitor platelet counts before ITVISMA injection and on a regular basis afterwards (at least weekly for the first month and as clinically indicated until platelet counts return to baseline) [see Dosage and Administration (2.1, 2.4)] .

5.3Peripheral Sensory Neuropathy Peripheral sensory neuropathy has occurred with ITVISMA administration [see Adverse Reactions (6.1)] . Signs and symptoms may include numbness, tingling, prickling, or pain in the arms, hands, legs and/or feet, with onset seen at approximately three weeks post-injection in clinical studies. Consider complete neurologic evaluation and other testing and/or symptom ma… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The most common adverse reactions that occurred in at least 10% of patients were upper respiratory tract infection, upper gastrointestinal symptoms, pyrexia, and headache. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Gene Therapies at 1-833-828-3947 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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 product and may not reflect the rates observed in practice. The safety data described in this section reflects exposure of ITVISMA in two clinical studies, Study 1, a randomized, sham-controlled study which evaluated the safety of ITVISMA in 126 patients with spinal muscular atrophy (SMA) and Study 2, an open-label-single arm study which evaluated safety of ITVISMA in 27 patients with SMA who were previously treated with nusinersen (at least 4 months washout) or risdiplam (at least 15 days washout).

In Study 1, a total of 75 patients received a single intrathecal injection of ITVISMA at a fixed dose of 1.2 x 10 14 vg and 51 patients underwent a sham-procedure [see Clinical Studies (14)] . In Study 2, a total of 27 patients received a single intrathecal injection of ITVISMA at a fixed dose of 1.2 x 10 14 vg. The patients were followed for a duration of 52 weeks for both studies.

In Study 1, serious adverse reactions were reported in four patients (5%) including elevated liver enzymes (n=1), sensory disturbance (n=2), and vomiting (n=1). The most frequent adverse reactions occurring in ≥ 2% of patients in Study 1 are summarized in Table 3 below. Table 3: Adverse Reactions Occurring in ≥2% of Patients or with higher frequency in ITVISMA-treated Patients compared to Sham group in Study 1 Adverse reactions ITVISMA Sham (N = 75), n (%) (N = 51), n (%) * Is a composite that includes multiple related terms a) Two patients had ALT elevations of 20 times the upper limit of normal (ULN). b) Signs and symptoms that may be suggestive of dorsal root ganglion (DRG) toxicity occurred within 3 weeks of ITVISMA injection and stabilized but remained unresolved at the end of study period. c) Occurred 154 days after the sham procedure and resolved after 15 days without intervention.

Upper respiratory tract infection * 31 (41) 15 (29) Pyrexia 19 (25) 12 (24) Upper gastrointestinal symptoms * 20 (27) 8 (16) Hepatic enzyme increased * 6 (8) a 5 (10) Headache 8 (11) 2 (4) Dizziness 4 (5) 1 (2) Pain in extremity 3 (4) 1 (2) Thrombocytopenia * 3 (4) 0 Sensory disturbance * 2 (3) b 1 (2) c The safety evaluated in Study 2 did not identify any additional safety events with ITVISMA administration.

6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of ZOLGENSMA, a similar product containing the same active ingredient (onasemnogene abeparvovec) administered intravenously. Because these reactions are reported voluntarily, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders : thrombotic microangiopathy Hepatobiliary Disorders : acute liver failure (fatal and non-fatal), acute liver injury General Disorders and Administration Site Conditions : pyrexia, infusion-related reactions Investigations : troponin increased

🔄 Drug Interactions 82 words ▾

7 DRUG INTERACTIONS 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 )

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy 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.

8.2Lactation Risk Summary There is no information available on the presence of ITVISMA in human milk, the effects on the breastfed infant or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ITVISMA and any potential adverse effects on the breastfed child from ITVISMA or from the underlying maternal condition.

8.3Females and Males of Reproductive Potential Pregnancy Testing The pregnancy status of females of reproductive potential should be verified prior to treatment with ITVISMA [see Use in Specific Populations (8.1)] . Contraception Females of reproductive potential should use effective contraception (methods that result in less than 1% pregnancy rates) and should refrain from egg donation for 6 months following ITVISMA administration. Men capable of fathering a child should use a barrier method of contraception and should refrain from sperm donation for 3 months following ITVISMA administration.

Infertility There is no data on the effect of ITVISMA on human fertility. In animal fertility studies, onasemnogene abeparvovec did not impact fertility in male and female mice at a dose of 1.1 × 10 14 vg/kg administered intravenously [see Nonclinical Toxicology (13.1)] .

8.4Pediatric Use The safety and efficacy of ITVISMA have been established in pediatric patients 2 years of age and older. The use of ITVISMA was supported by data from one clinical study (Study 1) which enrolled 126 pediatric patients 2 years of age and older [see Adverse Reaction (6) and Clinical Studies (14)] . The safety and effectiveness of ITVISMA have not been established in pediatric patients younger than 2 years of age.

8.6Hepatic 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 (5.1)] .

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy 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.

🧒 Pediatric Use 74 words ▾

8.4Pediatric Use The safety and efficacy of ITVISMA have been established in pediatric patients 2 years of age and older. The use of ITVISMA was supported by data from one clinical study (Study 1) which enrolled 126 pediatric patients 2 years of age and older [see Adverse Reaction (6) and Clinical Studies (14)] . The safety and effectiveness of ITVISMA have not been established in pediatric patients younger than 2 years of age.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action ITVISMA is a non-replicating recombinant AAV vector that utilizes AAV9 capsid to deliver a functional copy of human survival motor neuron 1 gene (SMN1) . The transgene DNA persists largely in episomal form in the nucleus of transduced cells. Expression of the transgene is driven by a constitutive promoter (cytomegalovirus enhanced chicken-β-actin hybrid), resulting in continuous and sustained SMN expression.

SMA is caused by a bi-allelic mutation in the SMN1 gene, which results in insufficient SMN protein expression. By providing an alternative source of SMN protein expression in motor neurons, it is expected to promote the survival and function of transduced motor neurons.

12.2Pharmacodynamics There are no clinically relevant pharmacodynamics data for ITVISMA.

12.3Pharmacokinetics Nonclinical Biodistribution Intrathecal (IT) administration of onasemnogene abeparvovec to non-human primates (NHPs) at dose levels of 1.2 × 10 13 (equivalent to the clinical therapeutic dose), 3.0 × 10 13 , or 6.0 × 10 13 vector genomes (vg)/animal, resulted in biodistribution of the vector to all the CNS and peripheral tissues assessed. Vector DNA concentrations were highest in the liver, followed by the dorsal root ganglia (DRG) and spinal cord, with the lowest concentrations detected in the gonads.

Vector DNA concentrations in the spinal cord tended to remain stable between 6-weeks and 12-months post-administration at all dose levels assessed. IT or intra-cisterna magna administration of a tool scAAV9CB-GFP vector to adult NHPs resulted in the detection of vector DNA in the oocytes and ovarian stromal cells of females administered 1.0 × 10 13 and 3.0 × 10 13 vg/animal at 28-days post-administration of the product. In mice, intravenous, or intracerebroventricular administration of onasemnogene abeparvovec resulted in no detection of vector DNA in the germline cells of males and females at 24 weeks post-administration.

In non-human primates, high pre-existing serum anti-AAV9 antibody titers (corresponding to human titer values of up to approximately 1:25000) were not shown to affect scAAV9 vector (utilized in onasemnogene abeparvovec) DNA distribution in the spinal cord following IT administration. Clinical Vector Shedding ITVISMA vector shedding studies, which assess the amount of vector DNA eliminated from the body through saliva, urine, feces and nasal secretions were performed following intrathecal administration in 134 patients.

Vector DNA was detectable in shedding samples in 134 patients following IT injection of ITVISMA. Shedding of ITVISMA DNA was primarily via feces. Peak shedding in participants was observed within 10-, 3-, 2-, and 8 days post-dose for stool, urine, saliva and nasal secretion, respectively.

The majority of the vector DNA (> 90%) is excreted within 2 weeks after dose administration.

12.6Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of ITVISMA or of other AAV gene therapy products. In Study 1 and Study 2, anti-AAV9 antibody titers were evaluated in 102 patients following a single IT injection of ITVISMA.

In these studies, patients were required to have baseline anti-AAV9 antibody titers ≤ 1:50. Increases from baseline in anti-AAV9 antibody titers were reported in all patients with a median anti-AAV9 antibody titers of ≥ 1:819,200 at 12 months following ITVISMA injection in both studies. During the 12-month period following ITVISMA injection in Study 1 and Study 2, positive anti-SMN antibodies were observed in 5/75 (6.7%) and 2/27 (7.4%) of ITVISMA-treated patients, respectively.

There was no identified clinical effect of anti-SMN and anti-AAV9 antibodies on safety or efficacy of I… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 107 words ▾

12.1Mechanism of Action ITVISMA is a non-replicating recombinant AAV vector that utilizes AAV9 capsid to deliver a functional copy of human survival motor neuron 1 gene (SMN1) . The transgene DNA persists largely in episomal form in the nucleus of transduced cells. Expression of the transgene is driven by a constitutive promoter (cytomegalovirus enhanced chicken-β-actin hybrid), resulting in continuous and sustained SMN expression.

SMA is caused by a bi-allelic mutation in the SMN1 gene, which results in insufficient SMN protein expression. By providing an alternative source of SMN protein expression in motor neurons, it is expected to promote the survival and function of transduced motor neurons.

📦 How Supplied / Storage and Handling 147 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied ITVISMA is supplied as a sterile, preservative-free, clear to slightly opaque, colorless to faint white suspension for intrathecal injection. ITVISMA contains 4 × 10 13 vg per mL. Each carton of ITVISMA contains a single-dose vial with an extractable volume of not less than 3 mL, containing 1.2 × 10 14 vg.

Carton containing one 1.2 × 10 14 vg/3 mL (4 × 10 13 vg/mL) single-dose vial. Container (vial): NDC Number 71894-200-01 Package (carton): NDC Number 71894-200-02

16.2Storage and Handling Product is shipped and delivered frozen (≤ -60°C [-76°F]) in a single-dose clear vial. Upon receipt, immediately place the carton in a refrigerator at 2°C to 8°C (36°F to 46°F). ITVISMA is stable for 14 days from receipt when stored at 2°C to 8°C (36°F to 46°F). DO NOT REFREEZE. Must use within 14 days of receipt.

📋 Description 102 words ▾

11 DESCRIPTION ITVISMA (onasemnogene abeparvovec-brve) is a suspension of an adeno-associated viral vector-based gene therapy for intrathecal injection. It is a recombinant self-complementary AAV9 containing a transgene encoding the human survival motor neuron (SMN) protein, under the control of a cytomegalovirus enhancer/chicken-β-actin hybrid promoter. ITVISMA has a nominal concentration of 4 × 10 13 vg/mL.

Each vial contains an extractable volume of not less than 3 mL and the excipients 20 mM Tris (pH 8.0), 1 mM magnesium chloride (MgCl 2 ), 200 mM sodium chloride (NaCl) and 0.005% poloxamer 188. ITVISMA is packaged as a sterile suspension and contains no preservative.

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Hepatotoxicity Inform patients and caregivers that ITVISMA could increase liver enzyme levels. Inform patients and caregivers that patients will receive an oral corticosteroid medication before and after ITVISMA injection, and will undergo regular blood tests to monitor liver function. Advise patients and caregivers to contact their healthcare provider immediately if the patient’s skin and/or whites of the eyes appear yellowish, if the patient misses a dose of corticosteroid or vomits it up, or if the patient experiences a decrease in alertness [see Warnings and Precautions (5.1)] .

Vaccination Before and After ITVISMA Injection Advise patients and caregivers to consult with their healthcare provider to determine if adjustments to the patient’s vaccination schedule are necessary during corticosteroid use. Inform patients and caregivers that where feasible, the vaccination schedule should be adjusted appropriately to accommodate treatment with corticosteroid. Prophylaxis against influenza and RSV is recommended and vaccination status should be up-to-date prior to ITVISMA administration.

Please consult your health care provider [see Dosage and Administration (2.1), Drug Interactions (7)] . Concurrent Infections Patients and caregivers should be aware that an infection (e.g., cold, flu, gastroenteritis, otitis media, bronchiolitis, etc.) before or after ITVISMA injection could lead to more serious complications. Patients, caregivers and close contacts of patients should follow infection prevention practices (e.g., hand hygiene, coughing/sneezing etiquette, limiting potential contacts).

Advise patients and caregivers of the signs of a possible infection, such as coughing, wheezing, sneezing, runny nose, sore throat, or fever. Patients and caregivers should contact their healthcare provider immediately if the patient experiences any symptoms suggestive of infection before or after ITVISMA injection [see Dosage and Administration (2.1)] . Thrombocytopenia Inform patients and caregivers that ITVISMA could decrease blood platelet count and increase the risk of bruising or bleeding.

Inform patients and caregivers that decreases in platelet counts were observed within the first week after ITVISMA injection. Advise patients and caregivers to seek medical attention if the patient experiences unexpected bruising or bleeding [see Warnings and Precautions (5.2)] . Peripheral Sensory Neuropathy Inform patients and caregivers that peripheral sensory neuropathy has occurred with ITVISMA administration.

Advise patients and caregivers to contact their healthcare provider promptly if the patient experiences numbness, tingling, prickling, or pain in the arms, hands, legs and/or feet [see Warnings and Precautions (5.3)] . Thrombotic Microangiopathy Inform patients and/or caregivers that decreased blood platelet and red blood cell counts, acute kidney injury, and increased bruising or bleeding, which may be indicative of TMA, can occur. Advise patients and/or caregivers to seek immediate medical attention if the patient experiences unexpected bruising or bleeding, seizures, or decreased urine output [see Warnings and Precautions (5.4)] .

AAV Vector Integration and Risk of Tumorigenicity Inform patients and/or caregivers that there is a theoretical risk of tumorigenicity with AAV therapies such as ITVISMA. Advise patients and/or caregivers to contact their healthcare provider and Novartis Gene Therapies, Inc. (1-833-828-3947) if the patient who received ITVISMA develops a tumor [see Warnings and Precautions (5.6)] .

Contraception and Egg/Sperm Donation Advise women of childbearing potential to use an effective method of contraception and to refrain from egg donation for 6 months following ITVISMA injection. Advise men capable of fathering a child to use a barrier method of contraception and to refrain from sperm donation for 3 months following ITVISMA injection [see Use in Specific Populations (8.3)] . Manufactured by… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~1 min read ▾

12.3Pharmacokinetics Nonclinical Biodistribution Intrathecal (IT) administration of onasemnogene abeparvovec to non-human primates (NHPs) at dose levels of 1.2 × 10 13 (equivalent to the clinical therapeutic dose), 3.0 × 10 13 , or 6.0 × 10 13 vector genomes (vg)/animal, resulted in biodistribution of the vector to all the CNS and peripheral tissues assessed. Vector DNA concentrations were highest in the liver, followed by the dorsal root ganglia (DRG) and spinal cord, with the lowest concentrations detected in the gonads.

Vector DNA concentrations in the spinal cord tended to remain stable between 6-weeks and 12-months post-administration at all dose levels assessed. IT or intra-cisterna magna administration of a tool scAAV9CB-GFP vector to adult NHPs resulted in the detection of vector DNA in the oocytes and ovarian stromal cells of females administered 1.0 × 10 13 and 3.0 × 10 13 vg/animal at 28-days post-administration of the product. In mice, intravenous, or intracerebroventricular administration of onasemnogene abeparvovec resulted in no detection of vector DNA in the germline cells of males and females at 24 weeks post-administration.

In non-human primates, high pre-existing serum anti-AAV9 antibody titers (corresponding to human titer values of up to approximately 1:25000) were not shown to affect scAAV9 vector (utilized in onasemnogene abeparvovec) DNA distribution in the spinal cord following IT administration. Clinical Vector Shedding ITVISMA vector shedding studies, which assess the amount of vector DNA eliminated from the body through saliva, urine, feces and nasal secretions were performed following intrathecal administration in 134 patients.

Vector DNA was detectable in shedding samples in 134 patients following IT injection of ITVISMA. Shedding of ITVISMA DNA was primarily via feces. Peak shedding in participants was observed within 10-, 3-, 2-, and 8 days post-dose for stool, urine, saliva and nasal secretion, respectively.

The majority of the vector DNA (> 90%) is excreted within 2 weeks after dose administration.

🧬 Pharmacodynamics 11 words ▾

12.2Pharmacodynamics There are no clinically relevant pharmacodynamics data for ITVISMA.

🔬 Clinical Studies ~2 min read ▾

14 CLINICAL STUDIES The efficacy of ITVISMA was evaluated in a randomized, double-blind, sham-controlled study (Study 1; NCT05089656). The study enrolled patients with spinal muscular atrophy (SMA) who were treatment-naive, and able to sit but never able to walk independently. Patients with elevated (reference to > 1:50) baseline serum anti-AAV9 antibody titer were excluded.

A total of 136 patients were randomized in 3:2 ratio to receive either ITVISMA at a dose of 1.2 x 10 14 vg by single lumbar intrathecal injection or sham procedure. Randomization was stratified by age and pre-treatment Hammersmith Functional Motor Scale – Expanded (HFMSE) score at screening. A total of 126 patients received the assigned treatment and were included in the efficacy evaluation.

The demographic characteristics of the population were as follows: the mean age was 6 years (range 2 to 17 years), 62 patients (49%) were male, 74 patients (59%) were Asian, 14 patients (11%) were White, 9 patients (7%) were Black or African American, and 7 patients (6%) were American Indian or Alaska Native, 22 patients (18%) were of “unknown” race. One hundred and twenty-two patients (97%) had confirmed biallelic deletion (0 copies) of the SMN1 gene, while 4 patients (3%) had 1 copy. Patients' highest motor function ever achieved were as follows: 66 patients (52%) sitting without support, 33 patients (26%) standing with assistance, 24 patients (19%) walking with assistance, and 3 patients (2%) standing independently.

At baseline, the mean HFMSE total score was 17.97 (range 1.0 - 41.0) and 18.17 (range 2.0 - 42.5) in the ITVISMA-treated group and sham group, respectively. The primary endpoint was the change from baseline in HFMSE total score at the end of follow-up, defined as the average of the Week 48 and Week 52 assessment, in ITVISMA compared to sham. The HFMSE evaluates motor function in patients with SMA who have limited ambulation, comprising of 33 graded items that assess various motor skills ranging from sitting to using the stairs.

Each item is scored from 0-2, with a maximum total score of 66. Higher scores indicate better motor function. The efficacy results from Study 1 are summarized in Table 4 below.

Table 4: Efficacy Results from the Study 1 (n=126) Endpoint ITVISMA (N = 75) Sham (N = 51) Treatment Difference ITVISMA-Sham (95% CI) p-value CI = confidence interval 1 Assessed using the Full Analysis Set (FAS) population, which included all participants who were dosed with ITVISMA (n=75) or who underwent sham procedure (n=51). The follow-up period was defined as the average of the Week 48 and Week 52 assessment. 2 Least squares (LS) mean.

3 Estimated using a linear mixed model repeated measures (MMRM) model with the observed change from Baseline in HFMSE total score at all post-baseline visits as the dependent variable. The fixed effects included treatment, visit, treatment by visit interaction, the strata, and the baseline HFMSE total score as covariate. An unstructured covariance matrix was used.

4 Standard error of the mean (SEM) Mean change from baseline in HFMSE total score at the end of follow-up 1, 2, 3 2.39 (0.439) 4 0.51 (0.532) 4 1.88 (0.51 – 3.25) 0.0074

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility No animal studies have been performed to evaluate the effects of onasemnogene abeparvovec on carcinogenesis or mutagenesis. In fertility and early embryonic development studies conducted in male and female mice, onasemnogene abeparvovec DNA was detected in gonadal tissues of mice administered onasemnogene abeparvovec intravenously at dose levels of 1.1x10 13 or 1.1 × 10 14 vector genomes (vg)/kg body weight. No adverse effects on male or female fertility, fecundity, or mating indices were observed.

No evidence of germ cell transduction or germline transmission was reported. [see Use in Specific Populations (8.3)]

13.2Animal Toxicology and/or Pharmacology A single IT dose of onasemnogene abeparvovec was administered at three dose levels: 1.20 × 10 13 vg/animal (equivalent to the clinical therapeutic dose), 3.0 × 10 13 vg/animal, and 6.0 × 10 13 vg/animal. At 6 weeks post-administration, all dose levels resulted in acute, minimal to moderate mononuclear cell inflammation and neuronal degeneration across multiple anatomical sites, including the cerebrum, cerebellar white matter, brain stem, dorsal root ganglia, and various nerve structures (trigeminal, dorsal spinal, spinal, and peripheral nerves).

Additionally, axonal degeneration and/or gliosis was observed in the spinal cord. These findings partially or fully resolved by 12 months post-administration and had no correlative clinical observations. Elevated liver enzyme levels (aspartate and alanine amino transferase) and single cell necrosis of hepatocytes were observed in select NHPs at 6 weeks post-administration but resolved by 12 months post-administration.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 97 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility No animal studies have been performed to evaluate the effects of onasemnogene abeparvovec on carcinogenesis or mutagenesis. In fertility and early embryonic development studies conducted in male and female mice, onasemnogene abeparvovec DNA was detected in gonadal tissues of mice administered onasemnogene abeparvovec intravenously at dose levels of 1.1x10 13 or 1.1 × 10 14 vector genomes (vg)/kg body weight. No adverse effects on male or female fertility, fecundity, or mating indices were observed.

No evidence of germ cell transduction or germline transmission was reported. [see Use in Specific Populations (8.3)]

📄 Package Label / Principal Display Panel 98 words ▾

PRINCIPAL DISPLAY PANEL NDC 71894-200-02 Rx only onasemnogene abeparvovec-brve itvisma ® 1.2 × 10 14 vector genomes/ 3 mL (4 x 10 13 vector genomes (vg)/mL) Sterile solution for Intrathecal Injection Only One Single-dose Vial Must use within 14 days of receipt DO NOT SHAKE | DO NOT REFREEZE NOVARTIS PRINCIPAL DISPLAY PANEL NDC 71894-200-02 Rx only onasemnogene abeparvovec-brve itvisma® Injection 1.2 × 1014 vector genomes/ 3 mL (4 x 1013 vector genomes (vg)/mL) Sterile solution for Intrathecal Injection Only One Single-dose Vial Must use within 14 days of receipt DO NOT SHAKE | DO NOT REFREEZE NOVARTIS

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

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