BRIEF SUMMARY

AVACINCAPTAD- (Aug 2023)-

Indn-   To treat c atrophy scondary   macular degeneration

Dosage-  recommended dose for IZERVAY is 2 mg (0.1 mL of 20 mg/mL solution) administered by intravitreal injection to each  eye once monthly (approximately every 28 ± 7 days) for up to 12 months

ADR- adverse reactions  conjunctival hemorrhage (13%), increased IOP (9%), blurred vision (8%) and neovascular age-related macular degeneration (7%

DI Ocular or periocular infections,  Active intraocular inflammation

CI Ocular or periocular infections,  Active intraocular inflammation

Pat infm- patients are at risk of developing neovascular AMD, endophthalmitis, elevated intraocular pressure and retinal detachments.

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U.S.  APPROVED DRUGS DURING 2023                                        

Serial No 31

Name-                       IZERVAY

Acive  Ingredient -   Avacincaptad

Pharmacological clssificiation-        To treat  geographic atrophy sscondary  related                                                                 macular degeneration                                                                                                                                                                              

 Date of Approval-         8/4/2023

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use                                 IZERVAY safely and effectively.

See full prescribing information for IZERVAY. IZERVAY™ (avacincaptad pegol intravitreal solution)

Initial U.S. Approval: 2023

INDICATIONS AND USAGE-

 IZERVAY is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD)

DOSAGE AND ADMINISTRATION-

 The recommended dose for IZERVAY is 2 mg (0.1 mL of 20 mg/mL solution) administered by intravitreal injection to each affected eye once monthly (approximately 28 ± 7 days) for up to 12 months

DOSAGE FORMS AND STRENGTHS-

 Intravitreal solution: 20 mg/mL in a single-dose vial 

ADVERSE REACTIONS-

 The most common adverse reactions were conjunctival hemorrhage (13%), increased IOP (9%), blurred vision (8%) and neovascular age-related macular degeneration (7%)

 To report SUSPECTED ADVERSE REACTIONS, contact IVERIC bio, Inc. at 1-800-707-4479 or FDA at 1-800-FDA

CONTRAINDICATIONS-

 Ocular or periocular infections

 Active intraocular inflammation

WARNINGS AND PRECAUTIONS-

 Endophthalmitis and Retinal Detachments

 Neovascular AMD

 Increase in Intraocular Pressure (IOP)

DOSAGE AND ADMINISTRATION

1. General Dosing Information IZERVAY must be administered by a qualified physician.

2. Recommended Dosage

The recommended dose for IZERVAY is 2 mg (0.1 mL of 20 mg/mL solution) administered by intravitreal injection to each affected eye once monthly (approximately every 28 ± 7 days) for up to 12 months

PATIENT COUNSELING INFORMATION

Advise patients that following IZERVAY administration, patients are at risk of developing neovascular AMD, endophthalmitis, elevated intraocular pressure and retinal detachments.

If the eye becomes red, sensitive to light, painful, or if a patient develops a change in vision, instruct the patient to seek immediate care from an ophthalmologist

Patients may experience temporary visual disturbances and blurring after an intravitreal injection with IZERVAY and the associated eye examinations 

. Advise patients not to drive or use machinery until visual function has recovered sufficiently. IZERVAY™ (avacincaptad pegol intravitreal solution)

Manufactured by: IVERIC bio, Inc. Parsippany, NJ 07054

CLINICAL PHARMACOLOGY

1. Mechanism of Action-

Avacincaptad pegol is an RNA aptamer, a PEGylated oligonucleotide that binds to and inhibits complement protein C5.

By inhibiting C5, avacincaptad pegol may prevent its cleavage to C5a and C5b thus decreasing membrane attack complex (MAC) formation. 

2. Pharmacodynamics Increased GA area growth is reflective of loss of photoreceptors and AMD disease progression.

Reductions in the rate GA growth were observed from baseline through the first year of treatment across avacincaptad pegol treatment groups in studies GATHER1 and GATHER2.

3 Pharmacokinetics

Absorption/Distribution-

Following a single dose of avacincaptad pegol, maximum avacincaptad pegol plasma concentrations (Cmax) are estimated to occur approximately 7 days post-dose and mean (CV%) free avacincaptad pegol plasma Cmax is estimated to be 68.4 ng/mL (57.8%) in neovascular AMD (nAMD) patients.

Metabolism/Elimination-

Metabolism and elimination of avacincaptad pegol has not been fully characterized. Avacincaptad pegol is expected to be catabolized by endonucleases and exonucleases to oligonucleotides of shorter lengths which may be excreted renally, in similar manner to the elimination of endogenous RNA.

The estimated apparent systemic half-life of avacincaptad pegol is approximately 12 days.

Specific Populations-

Following repeat monthly intravitreal dose administration of 2 mg avacincaptad pegol, no differences in the systemic pharmacokinetics of avacincaptad pegol were observed based on age, gender, and body weight.

No special dosage modification is required for any of the populations that have been studied (e.g., age, gender, and body weight).

The effect of severe renal impairment or any degree of hepatic impairment on the pharmacokinetics of avacincaptad pegol is unknown.

As significant increases in plasma avacincaptad pegol exposures are not expected with intravitreal route of administration, no dosage adjustment is needed based on renal or hepatic impairment status.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary

There are no adequate and well-controlled studies of IZERVAY administration in pregnant women. The use of IZERVAY may be considered following an assessment of the risks and benefits..

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

2. Lactation Risk Summary There is no information regarding the presence of avacincaptad pegol in human milk, the effects of the drug on the breastfed infant, or the effects of avacincaptad pegol on milk production.

Many drugs are transferred in human milk with the potential for absorption and adverse reactions in the breastfed child.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for IZERVAY, and any potential adverse effects on the breastfed infant from IZERVAY

3. Pediatric Use-

Safety and effectiveness of IZERVAY in pediatric patients have not been established.

4. Geriatric Use-

Of the total number of patients who received IZERVAY in the two clinical trials, 90% (263/292) were =65 years and 61% (178/292) were =75 years of age.

No significant differences in efficacy or safety of avacincaptad pegol were seen with increasing age in these studies. No dose adjustment is required in patients 65 years and above.