Sir,
Geographic atrophy (GA) is a chronic progressive degeneration of the macula and according to global estimates, GA affects over 5 million individuals globally, accounting for roughly 25% of legal blindness cases in the United Kingdom, and 20% of cases in North America.[1] GA can lead to irreversible vision loss, one of the most common retinal pathologies that has impacted an estimated 1.5 million people in the United States.[2] FDA-approved drugs launched this year have had a major impact on GA and now have possibly become rivals as Izervay has overcome the side effects of Syfovre, the monthly intraocular injection that reports to have caused retinal vasculitis.[3]
Izervay is one of just two GA medications on the market right now, the other being Syfovre, which obtained FDA approval in February. The potential development of retinal vasculitis, a blinding condition, has caused the company to lose over two-thirds of their value and affected the prescription of Syfovre.[4] Both Izervay and Syfovre have a slight but elevated risk of causing the neovascularization in the eye, which may necessitate further treatment and the risk could increase with time [Table 1]. According to a research note written by Stifel analyst Annabel Samimy, the labelling for Izervay includes warnings about infections and high ocular pressure, and its safety profile has been noticeably cleaner than Syfovre. However, Iveric’s clearance was also based on research findings that were tracked for a year, and the 24-month safety update is yet to come.[5]
Table 1.
Differences between Izervay and Syfovre
| Characteristic | Izervay | Syfovre |
|---|---|---|
| Mechanism of action | Complement protein-C5 inhibition, preventing the cleavage of C5 to C5a and C5b, that takes part in the formation of MAC | Drug binds to complement C3 and C3b fragments, resulting in inhibition of the complement activation |
| Pharmacodynamics | Reduction in the growth rate of GA during the baseline year, increased GA area growth is reflective of loss of photoreceptors and AMD disease progression | IVT administration following the subcutaneous administration did not result in QT prolongation |
| Pharmacokinetics | ||
| Absorption/distribution | Cmax is estimated to occur approximately 7 days’ postdose, the mean plasma Cmax is estimated to be 68.4 ng/mL. the predicted steady-state avacincaptad pegol Cmax is 83.9 ng/mL | Tmax is between 7 and 14 days volume of distribution is approximately 1.85 L following IVT administration |
| Elimination/metabolism | Systemic half-life of avacincaptad pegol is approximately 12 days, and expected to be excreted renally | The geometric mean half-life of elimination is 4.5 days, and the CL is 0.284 L/day |
| Dosage forms and strength | It is a clear to slightly opalescent-colorless to slightly yellow solution in a single-dose vial The recommended dose for Izervay is 2 mg (in 0.1 mL of 20 mg/mL solution) |
It is a colorless to light yellow aqueous solution in a single-dose vial The recommended dose for Syfovre is 15 mg (0.1 mL of 150 mg/mL solution) |
| Indications | Geographic atrophy secondary to AMD | Geographic atrophy secondary to AMD |
| Immunogenicity | Not yet evaluated | There is a low incidence of anti-pegcetacoplan peptide antibodies |
| Side effects | Ocular and periocular infections, active intraocular inflammation endophthalmitis and retinal detachment, neovascular AMD, increase in intraocular pressure | Ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage |
| Contraindications | Ocular or periocular infection and active intraocular inflammation | Ocular or periocular infection and active intraocular inflammation |
| Cost | $2100 for monthly dose | $2190 for every 25–60 days |
MAC=Membrane attack complex, GA=Geographic atrophy, AMD=Age-related macular degeneration, CL=Clearance, IVT=Intravitreal, QT=QT interval in ECG, Cmax=Maximum plasma concentration / Peak plasma concentration, Tmax=Time to peak drug concentration
Izervay and Syfovre are the two GA medications on the market currently. When Syfovre was approved in February, a good number of peak sales were expected. However, reports of intraocular inflammation resulting from the drug have weakened its first-to-market advantage. Because both medications function in various ways, patients and health-care professionals can select the course of treatment that could be most effective for them.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
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