Voretigene neparvovec

Voretigene neparvovec
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sonya Gelfand

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Black Box Warning

Warning Title See full prescribing information for complete Boxed Warning. Condition Name: (Content)

Overview

Voretigene neparvovec is a Acetylcholine release inhibitor, Adrenergic receptor agonist that is FDA approved for the (type of indication of drug) of a list of indications, separated by commas.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include a list of adverse reactions, separated by commas..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Condition 1

• Dosing Information

• (Dosage)

Condition 2

• Dosing Information

• (Dosage)

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition 1

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

• (Dosage)

Condition 2

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

• (Dosage)

Non–Guideline-Supported Use

Condition 1

• Dosing Information

• (Dosage)

Condition 2

• Dosing Information

• (Dosage)

Condition 3

• Dosing Information

• (Dosage)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition 1

• Dosing Information

• (Dosage)

Condition 2

• Dosing Information

• (Dosage)

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition 1

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

• (Dosage)

Condition 2

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

• (Dosage)

Non–Guideline-Supported Use

Condition 1

• Dosing Information

• (Dosage)

Condition 2

• Dosing Information

• (Dosage)

Condition 3

• Dosing Information

• (Dosage)

Contraindications

CONTRAINDICATIONS

Warnings

Warning Title See full prescribing information for complete Boxed Warning. Condition Name: (Content)

Conidition 1

(Description)

Conidition 2

(Description)

Conidition 3

(Description)

Adverse Reactions

Clinical Trials Experience

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

(list/description of adverse reactions)

Respiratory

(list/description of adverse reactions)

Gastrointestinal

(list/description of adverse reactions)

Hypersensitive Reactions

(list/description of adverse reactions)

Miscellaneous

(list/description of adverse reactions)

Condition 2

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

(list/description of adverse reactions)

Respiratory

(list/description of adverse reactions)

Gastrointestinal

(list/description of adverse reactions)

Hypersensitive Reactions

(list/description of adverse reactions)

Miscellaneous

(list/description of adverse reactions)

Postmarketing Experience

(Description)

Drug Interactions

• Drug 1
• Drug 2
• Drug 3
• Drug 4
• Drug 5

Drug 1

(Description)

Drug 2

(Description)

Drug 3

(Description)

Drug 4

(Description)

Drug 5

(Description)

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): (Description)
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Voretigene neparvovec in women who are pregnant.

Labor and Delivery

(Description)

Nursing Mothers

(Description)g

Pediatric Use

(Description)

Geriatic Use

(Description)

Gender

(Description)

Race

(Description)

Renal Impairment

(Description)

Hepatic Impairment

(Description)

Females of Reproductive Potential and Males

(Description)

Immunocompromised Patients

(Description)

Others

(Description)

Administration and Monitoring

Administration

(Oral/Intravenous/etc)

Monitoring

Condition 1

(Description regarding monitoring, from Warnings section)

Condition 2

(Description regarding monitoring, from Warnings section)

Condition 3

(Description regarding monitoring, from Warnings section)

IV Compatibility

There is limited information regarding the compatibility of Voretigene neparvovec and IV administrations.

Overdosage

Acute Overdose

Signs and Symptoms

(Description)

Management

(Description)

Chronic Overdose

Signs and Symptoms

(Description)

Management

(Description)

Pharmacology

Voretigene neparvovec
Systematic (IUPAC) name
?
Identifiers
CAS number	?
ATC code	S01XA
PubChem	?
Chemical data
Formula	?
Mol. mass	?
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?(US)
Legal status	[[Prescription drug|Template:Unicode-only]](US)
Routes	subretinal injection

Mechanism of Action

• LUXTURNA is designed to deliver a normal copy of the gene encoding the human retinal pigment epithelial 65 kDa protein (RPE65) to cells of the retina in persons with reduced or absent levels of biologically active RPE65. The RPE65 is produced in the retinal pigment epithelial (RPE) cells and converts all-trans-retinol to 11-cis-retinol, which subsequently forms the chomophore, 11-cis-retinal, during the visual (retinoid) cycle. The visual cycle is critical in phototransduction, which refers to the biological conversion of a photon of light into an electrical signal in the retina. Mutations in the RPE65 gene lead to reduced or absent levels of RPE65 isomerohydrolase activity, blocking the visual cycle and resulting in impairment of vision.

Structure

There is limited information regarding Voretigene neparvovec Structure in the drug label.

Pharmacodynamics

• Injection of LUXTURNA into the subretinal space results in transduction of some retinal pigment epithelial cells with a cDNA encoding normal human RPE65 protein, thus providing the potential to restore the visual cycle.

Pharmacokinetics

Biodistribution (within the body) and Vector Shedding (excretion/secretion)

• LUXTURNA vector DNA levels in various tissues and secretions were determined using a quantitative polymerase chain reaction (qPCR) assay.

Nonclinical data

• Biodistribution of LUXTURNA was evaluated at three months following subretinal administration in non-human primates. The highest levels of vector DNA sequences were detected in intraocular fluids (anterior chamber fluid and vitreous) of vector-injected eyes. Low levels of vector DNA sequences were detected in the optic nerve of the vector-injected eye, optic chiasm, spleen and liver, and sporadically in the lymph nodes. Vector DNA sequences were not detected in the gonads.

Clinical data

• LUXTURNA vector shedding and biodistribution were investigated in a study measuring LUXTURNA DNA in tears from both eyes, and from serum, and whole blood of subjects in Study 2. In summary, LUXTURNA vector was shed transiently and at low levels in tears from the injected eye in 45% of the subjects in Study 2, and occasionally (7%) from the uninjected eye until Day 3 post-injection.
• In 29 subjects who received bilateral administrations, LUXTURNA vector DNA was present in tear samples of 13 subjects (45%). Peak levels of vector DNA were detected in the tear samples on Day 1 post-injection, after which no vector DNA was detected in a majority of the subjects (8 of 13). Three subjects (10%) had vector DNA in tear samples until Day 3 post-injection, and two subjects (7%) had vector DNA in tear samples for around two weeks post-injection. In another two subjects (7%), vector DNA was detected in tear samples from the uninjected (or previously injected) eye until Day 3 post-injection. Vector DNA was detected in serum in 3/29 (10%) subjects, including two with vector DNA in tear samples up to Day 3 following each injection.

Specific Populations

• No pharmacokinetic studies with LUXTURNA have been conducted.

Drug Interaction Studies

• No interaction studies have been performed with LUXTURNA.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

• No animal studies have been conducted to evaluate the effects of LUXTURNA on carcinogenesis, mutagenesis, and impairment of fertility.

Animal Toxicology and/or Pharmacology

• Bilateral, simultaneous subretinal administration of LUXTURNA was well tolerated at dose levels up to 8.25 x 10¹⁰ vg per eye in dogs with a naturally occurring RPE-65 mutation and 7.5 x 10¹¹ vg (5 times higher than the recommended human dose level) per eye in non-human primates (NHPs) with normal-sighted eyes. In both animal models, bilateral, sequential subretinal administrations, where the contralateral eye was injected following the first eye, were well tolerated at the recommended human dose level of 1.5 x 10¹¹ vg per eye. In addition, dogs with with the RPE-65 mutation displayed improved visual behavior and pupillary responses. Ocular histopathology showed only mild changes, which were mostly related to healing from the surgical administration procedure. Other findings observed following subretinal injection of LUXTURNA in dogs and NHPs included occasional and isolated inflammatory cells in the retina, with no apparent retinal degeneration. Dogs not previously exposed to AAV2 vectors developed antibodies to the AAV2 capsid following a single administration of LUXTURNA, whereas NHPs did not.

Clinical Studies

• The efficacy of LUXTURNA in pediatric and adult patients with biallelic RPE65 mutation-associated retinal dystrophy was evaluated in an open-label, two-center, randomized trial (Study 2). Of the 31 enrolled subjects, 21 subjects were randomized to receive subretinal injection of LUXTURNA. One subject discontinued from the study prior to treatment. Ten subjects were randomized to the control (non-intervention) group. One subject in the control group withdrew consent and was discontinued from the study. The nine subjects who were randomized to the control group were crossed over to receive subretinal injection of LUXTURNA after one year of observation. The average age of the 31 randomized subjects was 15 years (range 4 to 44 years), including 64% pediatric subjects (n=20, age from 4 to 17 years) and 36% adults (n=11). The 31 randomized subjects included 13 males and 18 females. Sixty-eight percent (68%) of the subjects were White, 16% were Asian, 10% were American Indian or Alaska Native, and 6% were Black or African-American. Bilateral subretinal injections of LUXTURNA were administered sequentially in two separate surgical procedures with an interval of 6 to 18 days.
• The efficacy of LUXTURNA was established on the basis of multi-luminance mobility testing (MLMT) score change from Baseline to Year 1. The MLMT was designed to measure changes in functional vision, as assessed by the ability of a subject to navigate a course accurately and at a reasonable pace at different levels of environmental illumination. The MLMT was assessed using both eyes and each eye separately at one or more of seven levels of illumination, ranging from 400 lux (corresponding to a brightly lit office) to 1 lux (corresponding to a moonless summer night). Each light level was assigned a score code ranging from 0 to 6. A higher score indicated that a subject was able to pass the MLMT at a lower light level. A score of -1 was assigned to subjects who could not pass MLMT at a light level of 400 lux. The MLMT of each subject was videotaped and assessed by independent graders. The MLMT score was determined by the lowest light level at which the subject was able to pass the MLMT. The MLMT score change was defined as the difference between the score at Baseline and the score at Year 1. A positive MLMT score change from Baseline to Year 1 visit indicated that the subject was able to complete the MLMT at a lower light level.
• Additional clinical outcomes were also evaluated, including full-field light sensitivity threshold (FST) testing, visual acuity, and visual fields.
• Table 2 summarizes the median MLMT score change from Baseline to Year 1 in the LUXTURNA treatment group as compared to the control group. A median MLMT score of 2 or greater was observed in the LUXTURNA treatment group, while a median MLMT score change of 0 was observed in the control group, when using both eyes or the first-treated eye. An MLMT score change of two or greater is considered a clinically meaningful benefit in functional vision.

This image is provided by the National Library of Medicine.

• Table 3 shows the number and percentage of subjects with different magnitudes of MLMT score change using both eyes at Year 1. Eleven of the 21 (52%) subjects in the LUXTURNA treatment group had an MLMT score change of two or greater, while one of the ten (10%) subjects in the control group had an MLMT score change of two.

This image is provided by the National Library of Medicine.

• Figure 6 shows MLMT performance of individual subjects using both eyes at Baseline and at Year 1.

This image is provided by the National Library of Medicine.

• Analysis of white light FST testing showed statistically significant improvement from Baseline to Year 1 in the LUXTURNA treatment group compared to the control group. The change in visual acuity from Baseline to Year 1 was not significantly different between the LUXTURNA and control groups.
• Figure 7 shows the effect of LUXTURNA over the two-year period in the LUXTURNA treatment group, as well as the effect in the control group after crossing over to receive subretinal injection of LUXTURNA. A median MLMT score change of two was observed for the LUXTURNA treatment group at Day 30, and this effect was sustained over the remaining follow-up visits throughout the two-year period. For the control group, a median MLMT score change of 0 was observed at all four follow-up visits during the first year. However, after crossing-over to receive subretinal injection of LUXTURNA, the subjects in the control group showed a similar response to LUXTURNA as compared to the subjects in the LUXTURNA treatment group.

This image is provided by the National Library of Medicine.

How Supplied

• Each carton of LUXTURNA (NDC 71394 – 415-01) contains one single-dose vial of the LUXTURNA (NDC 71394 – 065-01, 0.5 mL extractable volume) and two vials of Diluent (NDC 71394 – 716-01, 1.7 mL extractable volume in each vial). LUXTURNA contains 5 x 10¹² vector genomes (vg) per mL, requires a 1:10 dilution prior to administration.

Storage

• Store LUXTURNA and Diluent frozen at ≤ -65 °C.
• Following thaw of the vials, store at room temperature. Store diluted LUXTURNA at room temperature.
• LUXTURNA is an adeno-associated virus vector-based gene therapy. Follow universal biohazard precautions for handling.

Images

Drug Images

{{#ask: Page Name::Voretigene neparvovec |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

{{#ask: Label Page::Voretigene neparvovec |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

• Advise patients and/or their caregivers of the following risks.
• Endophthalmitis and other eye infections

• Serious infection can occur inside of the eye and may lead to blindness. In such cases, there is an urgent need for management without delay. Advise patients to call their healthcare provider if they experience new floaters, eye pain, or any change in vision.

• Permanent decline in visual acuity

• Permanent decline in visual acuity may occur following subretinal injection of LUXTURNA. Advise patients to contact their healthcare provider if they exprience any change in vision.

• Retinal abnormalities

• Treatment with LUXTURNA may cause some defects in the retina such as a small tear or a hole in the area or vicinity of the injection. Treatment may cause thinning of the central retina or bleeding in the retina. Advise patients to follow up with their healthcare provider on a regular basis and report any symptoms such as decreased vision, blurred vision, flashes of light, or floaters in their vision without delay.

• Increased intraocular pressure

• Treatment with LUXTURNA may cause transient or persistent increase in intraocular pressure. If untreated, such increases in intraocular pressure may cause blindness. Advise patients to follow-up with their healthcare provider to detect and treat any increase in intraocular pressure.

• Expansion of intraocular air bubbles

• Advise patients to avoid air travel, travel to high elevations or scuba diving until the air bubble formed following administration of LUXTURNA has completely dissipated from the eye. A change in altitude while the air bubble is still present may cause irreversible damage.

• Cataract

• Advise patients that following treatment with LUXTURNA, they may develop a new cataract, or any existing cataract may get worse.

• Shedding of LUXTURNA

• Transient and low level shedding of LUXTURNA may occur in patient tears. Advise patients and/or their caregivers on proper handling of waste material generated from dressing, tears and nasal secretion, which may include storage of waste material in sealed bags prior to disposal. These handling precautions should be followed for up to 7 days following LUXTURNA administration.

Precautions with Alcohol

Alcohol-Voretigene neparvovec interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

• Luxturna

Look-Alike Drug Names

There is limited information regarding Voretigene neparvovec Look-Alike Drug Names in the drug label.

Drug Shortage Status

Drug Shortage

Price

References

The contents of this FDA label are provided by the National Library of Medicine.