Revakinagene Taroretcel-lwey (Monograph)

Brand name: Encelto
Drug class: Gene Therapy

Revakinagene taroretcel-lwey is an allogeneic encapsulated cell-based gene therapy.

Uses for Revakinagene Taroretcel-lwey

Revakinagene taroretcel-lwey has the following uses:

Revakinagene taroretcel-lwey is indicated for the treatment of adults with idiopathic macular telangiectasia type 2 (MacTel). Revakinagene taroretcel-lwey has been designated an orphan drug by FDA for the treatment of MacTel.

Efficacy of revakinagene taroretcel-lwey was evaluated in 2 randomized, multicenter, sham-controlled studies in adults with MacTel and a photoreceptor inner segment/outer segment (IS/OS PR) break (loss) in ellipsoid zone (EZ) between 0.16 and 2.00 mm² measured by spectral domain-optical coherence tomography (SD-OCT) and best corrected visual acuity (BCVA) of 54-letter score or better (20/80 or better) as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at screening. Patients with neovascular MacTel were excluded from these studies. Patients were randomized to receive revakinagene taroretcel-lwey intravitreal implant or sham procedure under standard surgical procedures. The primary efficacy outcome of both studies was rate of change in the area of EZ loss (IS/OS, macular PR loss) over 24 months, as measured by SD-OCT. The rate of change in EZ area loss from baseline to 24 months with revakinagene taroretcel-lwey compared with sham was 0.075 versus 0.166 in the first study, and 0.111 versus 0.160 in the second study; the differences observed were statistically significant.

Revakinagene Taroretcel-lwey Dosage and Administration

General

Revakinagene taroretcel-lwey is available in the following dosage form(s) and strength(s):

One single-dose implant containing 200,000 to 440,000 allogeneic retinal pigment epithelial cells expressing recombinant human ciliary neurotrophic factor (rhCNTF).

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

For intravitreal implantation only.

• Revakinagene taroretcel-lwey is intended for surgical intravitreal implantation under aseptic conditions by a qualified ophthalmologist.

• The recommended dose is one revakinagene taroretcel-lwey implant per affected eye containing 200,000 to 440,000 allogeneic retinal pigment epithelial cells expressing recombinant human ciliary neurotrophic factor (rhCNTF).

• Carefully inspect revakinagene taroretcel-lwey prior to use and refer to the Instructions for Use when preparing for and performing surgical placement or removal of revakinagene taroretcel-lwey.

Cautions for Revakinagene Taroretcel-lwey

Contraindications

• Patients with active or suspected ocular or periocular infections.

• Patients with known hypersensitivity to Endothelial Serum Free Media (Endo-SFM).

Warnings/Precautions

Severe Vision Loss

Severe vision loss defined as three or more lines of visual acuity loss [≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] has occurred following revakinagene taroretcel-lwey implantation. Monitor patients for signs and symptoms of vision loss and manage as clinically indicated.

Infectious Endophthalmitis

Infectious endophthalmitis may occur following revakinagene taroretcel-lwey implantation. Signs and symptoms of infectious endophthalmitis include progressively worsening eye pain, vision loss, or scleral and conjunctival injection. To mitigate the risk of endophthalmitis, use proper aseptic surgical technique for revakinagene taroretcel-lwey implantation. Monitor patients for signs or symptoms of infectious endophthalmitis. Remove revakinagene taroretcel-lwey implant if infectious endophthalmitis occurs and manage symptoms according to clinical practice.

Retinal Tear and Detachment

Retinal tears and retinal detachment may occur following revakinagene taroretcel-lwey implantation. Signs and symptoms of retinal tears include acute onset of flashing lights, floaters, and/or loss of visual acuity. Signs and symptoms of retinal detachment may include progressive visual field loss and/or loss of visual acuity. Use standard vitreoretinal surgical techniques during revakinagene taroretcel-lwey implantation to minimize the risk of retinal tears and retinal detachment. Monitor for any signs or symptoms of retinal tear and/or retinal detachment. Treat rhegmatogenous retinal detachment and retinal tears promptly. Remove revakinagene taroretcel-lwey implant if vitrectomy with a complete gas fill or silicone oil fill is required.

Vitreous Hemorrhage

Vitreous hemorrhage, which may result in temporary vision loss, has occurred following revakinagene taroretcel-lwey implantation. Patients receiving antithrombotic medication (e.g., oral anticoagulants, aspirin, nonsteroidal anti-inflammatory drugs) may be at increased risk of vitreous hemorrhage. To reduce the risk of vitreous hemorrhage, interrupt antithrombotic medications prior to the revakinagene taroretcel-lwey implantation. Vitrectomy surgery may be necessary to clear severe, recurrent, or non-clearing vitreous hemorrhage. If the patient has a late onset vitreous hemorrhage (greater than one year following revakinagene taroretcel-lwey implantation surgery), examine the revakinagene taroretcel-lwey implantation site for possible implant extrusion. If implant extrusion has occurred, surgically reposition revakinagene taroretcel-lwey.

Implant Extrusion

Implant extrusion through the initial scleral wound has occurred following revakinagene taroretcel-lwey implantation. Signs and symptoms of implant extrusion include recurrent uveitis, vitreous hemorrhage, eye pain more than one year after implantation, or visibility of titanium fixation loop under the conjunctiva. To reduce the risk of implant extrusion, carefully follow the specific surgical steps for revakinagene taroretcel-lwey implantation.

Evaluate patients after 6 months to confirm proper positioning of revakinagene taroretcel-lwey and then annually. If revakinagene taroretcel-lwey begins to extrude, surgically reposition to a proper scleral wound depth either in the same site or in the opposing inferior quadrant of the vitreous cavity.

Cataract Formation

Cataract formation, including cataract cortical, cataract nuclear, cataract subcapsular, cataract traumatic, and lenticular opacities, has occurred following revakinagene taroretcel-lwey implantation. To reduce the risk of cataract formation or progression, carefully follow the specific surgical steps for revakinagene taroretcel-lwey implantation.

Suture Related Complications

Suture related complications, including conjunctival erosions due to suture tips and suture knots, have occurred following revakinagene taroretcel-lwey implantation. To mitigate the risk of suture related complications, carefully follow the specific surgical steps for implantation and manage suture-related complications as clinically indicated.

Delayed Dark Adaptation

Delayed dark adaptation, a delay in the ability to adjust vision from a bright lighting condition to a dim lighting, has occurred following revakinagene taroretcel-lwey administration which remained unchanged for the duration of study follow up. Advise patients to take caution while driving and navigating in the dark.

Specific Populations

Pregnancy

There are no data on the use of revakinagene taroretcel-lwey in pregnant women. Endogenous ciliary neurotrophic factor is naturally found in maternal plasma, placental cells, and umbilical cord blood. It is not known if the use of revakinagene taroretcel-lwey increases CNTF above naturally occurring levels in these tissues.

In animal reproduction studies, subcutaneous administration of rhCNTF to pregnant rats and rabbits demonstrated no evidence of teratogenic effects on the fetus. However, when administered to rabbits at a dose level of 10ug/kg/day, a decrease in implantations and live fetuses was observed. When administered to rats at a dose level of 100 ug/kg/day a decrease in corpora lutea was observed.

The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Lactation

There is no data on the presence of revakinagene taroretcel-lwey in human milk, its effects on the breastfed infant, or its impact on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for revakinagene taroretcel-lwey and any potential adverse effects on the breastfed infant from rhCNTF or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of revakinagene taroretcel-lwey have not been established in pediatric patients.

Geriatric Use

There were 38 patients (32%) 65 years of age and older and two patients (1%) 75 years of age and older in Study 1 and Study 2 who received revakinagene taroretcel-lwey. Clinical studies of revakinagene taroretcel-lwey did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently than younger patients.

Common Adverse Effects

The most common adverse reactions (incidence ≥2%) were conjunctival hemorrhage, delayed dark adaptation, foreign body sensation, eye pain, suture related complications, miosis, conjunctival hyperemia, eye pruritus, ocular discomfort, vitreous hemorrhage, blurred vision, headache, dry eye, eye irritation, cataract progression or formation, vitreous floaters, severe vision loss, eye discharge, anterior chamber cell, iridocyclitis.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Revakinagene taroretcel-lwey secretes recombinant human ciliary neurotrophic factor (rhCNTF), which is one of several neurotrophic factors endogenously produced by neurons and supporting glial cells. Exogenous CNTF is thought to initially target Müller glia to trigger a cascade of signaling events that may promote photoreceptor survival; however, the mechanism of action for revakinagene taroretcel-lwey is not completely understood.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Patient Information).

• Advise patients that revakinagene taroretcel-lwey implantation may be associated with infectious endophthalmitis (eye infection), retinal tear and detachment (retina separates from the eye wall resulting in vision loss), vitreous hemorrhage (bleeding within the central cavity of the eye), implant extrusion, suture-related complications, cataract formation (clouding of the lens of the eye), severe vision loss, and delayed dark adaptation (ability of the eye to adjust from bright lighting conditions to dark lighting conditions).

• Instruct patients to seek immediate care from an ophthalmologist if they experience any signs or symptoms that could be associated with these events which may include an increase in floaters, the appearance of “spider webs”, flashing lights, sensitivity to light, loss of vision or visual field, increasing eye pain, progressive redness in the white of the eye, a sudden sensation that something is in their eye (i.e., foreign body sensation), or eye discharge.

• Advise patients that they may temporarily experience the following after revakinagene taroretcel-lwey implantation: mild sensation of something in the eye (i.e., foreign body sensation), eye redness, dryness, irritation, pain or discomfort, or blurred vision or floaters.

• Advise patients that delayed dark adaptation may be experienced for the length of time that revakinagene taroretcel-lwey is surgically placed.

• Advise patients of the risk of driving. Delayed dark adaptation may impair one's ability to see objects, pedestrians, or road signs when moving rapidly from a brightly lit environment to a dimly lit environment (for example, entering a tunnel during the daytime).

• Advise patients of the difficulty of navigating in the dark. Advise caution when moving from bright to dark areas, such as entering a dark room or stepping outside at dusk. Consider using flashlights, nightlights, or motion-activated lighting at home.

• Advise patients to consider wearing sunglasses or tinted lenses in bright environments to reduce the impact of transitioning from light to dark.

• Revakinagene taroretcel-lwey is magnetic resonance (MR) conditional. Advise patients that they have revakinagene taroretcel-lwey implanted in their eye and provide the patient with their implant card should they require Magnetic Resonance Imaging (MRI).

• Advise patients to not drive or use machinery until the eye shield has been removed and their ophthalmologist informs them that their vision has recovered to an acceptable level.

• Advise patients of the following postoperative care. Avoid heavy lifting (over 20 pounds) for 1 week. Keep water out of the eye (e.g., close eye while showering) for 1 week. Protect eyes by wearing glasses or protective eyewear during the day and using an eye shield at night for 1 week. Use a topical antibiotic solution at a frequency of 1 drop four times a day for 7 days.

• Instruct patients to use a steroid drop taper of prednisolone acetate 1% (or equivalent) starting the day after surgery with the following taper: 1 drop four times a day for the first 7 days; 1 drop three times a day for the next 7 days; 1 drop two times a day for the next 7 days; 1 drop once a day for the last 7 days.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Revakinagene taroretcel Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for revakinagene taroretcel.

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