Prademagene Zamikeracel (Monograph)

Brand name: Zevaskyn
Drug class: Gene Therapy

Introduction

Prademagene zamikeracel is an autologous cell-based gene therapy.

Uses for Prademagene Zamikeracel

Prademagene zamikeracel has the following uses:

Prademagene zamikeracel is indicated for the treatment of wounds in adult and pediatric patients with recessive dystrophic epidermolysis bullosa (RDEB) and has been designated an orphan drug by FDA for this use.

Efficacy of prademagene zamikeracel was evaluated in a multicenter, randomized, intrapatient-controlled study (VIITAL). The study compared prademagene zamikeracel with standard of care treatment in patients with wounds associated with RDEB. Patients were required to have at least one pair of matched, large and chronic wounds. Following single application of prademagene zamikeracel, 81% of the 43 treated wounds showed at least 50% healing at 6 months compared with 16% of the matched control wounds that were treated with standard of care. Prademagene zamikeracel therapy was also associated with statistically significant improvements in pain reduction from baseline to 6 months.

Prademagene Zamikeracel Dosage and Administration

General

Prademagene zamikeracel is available in the following dosage form(s) and strength(s):

Single-dose cellular sheets for topical application, each measuring 41.25 cm² (5.5 cm x 7.5 cm) and consisting of patient's own, viable, gene-modified cells that contain functional copies of the COL7A1 gene, which express collagen 7 (C7) protein. Up to 12 cellular sheets are supplied for each surgical session (supplied as up to 3 containers containing up to 4 sheets).

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 and Pediatric Patients

For autologous topical application on wounds only. For surgical application by a qualified healthcare provider,

• The recommended dose of prademagene zamikeracel is based on the surface area of the wound(s). One sheet of prademagene zamikeracel covers an area of 41.25 cm².

• Up to twelve prademagene zamikeracel sheets may be manufactured from the patient biopsies and supplied for potential use.

• Verify the patient’s identity prior to prademagene zamikeracel application.

• See full prescribing information for prademagene zamikeracel preparation and administration instructions.

Cautions for Prademagene Zamikeracel

Contraindications

None.

Warnings/Precautions

Hypersensitivity Reactions

Severe hypersensitivity reactions to vancomycin, amikacin, or product excipients may occur with prademagene zamikeracel application. Monitor for signs and symptoms of hypersensitivity reactions such as itching, swelling, hives, difficulty breathing, runny nose, watery eyes, nausea, and in severe cases, anaphylaxis and treat according to standard clinical practice.

Retroviral Vector (RVV)-mediated Insertional Oncogenesis

RVV-mediated insertional oncogenesis may potentially occur after treatment with prademagene zamikeracel. Monitor patients lifelong after treatment with prademagene zamikeracel for the development of malignancies. In the event that a malignancy occurs, contact Abeona Therapeutics Inc. at 1-844-888-2236 to obtain instructions on collecting patient samples for testing.

Transmission of Infectious Agents

Transmission of infectious disease or agents may occur with prademagene zamikeracel administration because it is manufactured using human and bovine-derived reagents, which are tested for human and animal viruses, bacteria, fungi, and mycoplasma before use. These measures do not eliminate the risk of transmitting these or other infectious diseases or agents.

Specific Populations

Pregnancy

There are no available data with prademagene zamikeracel use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with prademagene zamikeracel.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy at the time of treatment with prademagene zamikeracel.

Lactation

There is no information regarding the presence of prademagene zamikeracel in human milk, its effect on the breastfed infant, or its effects on milk production. Animal lactation studies have not been conducted with prademagene zamikeracel.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for prademagene zamikeracel and any potential adverse effects on the breast-fed infant from prademagene zamikeracel or from the underlying maternal condition.

Females and Males of Reproductive Potential

No studies were performed to evaluate the effect of prademagene zamikeracel on fertility.

Pediatric Use

The safety and effectiveness of prademagene zamikeracel have been established in pediatric patients. The use of prademagene zamikeracel in pediatric patients was supported by evidence from one clinical study which included two pediatric patients 6 years and 16 years of age.

Geriatric Use

The safety and effectiveness of prademagene zamikeracel have not been studied in geriatric patients ≥ 65 years of age.

Common Adverse Effects

The most common adverse reactions (incidence ≥5%) were procedural pain and pruritus.

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

In patients with recessive dystrophic epidermolysis bullosa (RDEB), both copies of the COL7A1 gene are mutated, resulting in the absence or low levels of biologically active C7 protein which form anchoring fibrils (AFs). The lack of AFs disrupts the connection between the epidermis and the dermis and causes skin fragility and other signs and symptoms of RDEB. Prademagene zamikeracel consists of a patient's own cells that have been gene-modified through RVV transduction to express the COL7A1 gene to produce the C7 protein. These cells are formed into cellular sheets for topical application onto wounds.

Advice to Patients

• Inform patients and/or caregivers that hypersensitivity reactions may occur with prademagene zamikeracel application. Advise patients and/or caregivers to seek immediate medical evaluation if any signs and symptoms of hypersensitivity reaction occur, such as itching, swelling, hives, difficulty breathing, runny nose, watery eyes, nausea, and in severe cases, anaphylaxis.

• Inform patients and/or caregivers about the possible risk of insertional oncogenesis and development of malignancies with prademagene zamikeracel application.

• Inform patients and/or caregivers about the possible risk of transmission of infectious agents with prademagene zamikeracel application.

• Advise patients to expect pain and itching at the treatment site during the healing process and to contact the treating physician if they experience fever, increased drainage, worsening pain and/or swelling or any other adverse effect at or around the treatment site.

• Advise patients to not disturb the surgical dressing covering the prademagene zamikeracel epidermal sheet for 5-10 days. Leave the post-procedure surgical dressing in place unless instructed otherwise by the treating physician.

• Advise patients to keep the dressing(s) dry. Do not submerge treated sites in water until the gauze of the prademagene zamikeracel falls off the treatment site. Gauze backing should fall off within 2-3 weeks of prademagene zamikeracel surgical application.

• Inform patients and/or caregivers that manufacturing failure may occur with autologous products. In case of a manufacturing failure, a second manufacturing of prademagene zamikeracel could be attempted with a new biopsy.

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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Related/similar drugs

Prademagene zamikeracel topical 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 prademagene zamikeracel topical.

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