Pegcetacoplan has launched already in the United States and Europe for PNH, a rare hematological disease. As one of the few drugs to have completed phase 3 trials for GA, pegcetacoplan is anticipated to be the first drug to launch for GA or “dry late age-related macular degeneration (AMD),” which has no approved pharmacotherapy. The U.S. Food and Drug Administration (FDA)’s granting of fast track status and priority review designation underscores the unmet need in this underserved patient population and the potential for pegcetacoplan to experience commercial success upon launch.
Subcutaneous pegcetacoplan generated $15.1 million in sales in 2021 following its launch in the United States in May 2021 to treat PNH. Additional global approvals for PNH will likely contribute to greater sales over the coming years, and the contribution of sales for PNH is likely to be smaller than that for GA.
If launched when expected, pegcetacoplan will be the first GA therapy to market. Its novel mechanism of action targets complement C3, which has been detected in drusen in the retina of GA patients and shown to induce VEGF expression. It has demonstrated the ability to delay GA progression, and its potential bimonthly dosing could prove to be an advantage over other competitors will monthly dosing only.
The New Drug Application (NDA) submitted to the U.S. FDA for GA was supported by results from phase 2 and 3 trials:
For adults with PNH who are anemic after treatment with a C5 inhibitor for at least three months:
• Marketing authorization: European Commission (EC)
For GA secondary to AMD:
• Priority Review designation: U.S. FDA
• Fast track designation: U.S. FDA
• Anticipated submission for marketing authorization: European Medicines Agency (EMA)
• PDUFA date (FDA)
Actual and expected launch:
• 2021: United States
• 2022: Europe
• 2023: United States
• 2024: Europe
Patents estimated to expire beginning in 2033
How will pegcetacoplan impact the market for PNH and GA?
What gaps in treatment does pegcetacoplan fill?
PNH is a rare, acquired, life-threatening blood disease that has historically required either frequent intravenous infusions or a bone marrow transplant in more severe cases, both related with high treatment burden. More convenient, longer-lasting treatments have only recently begun to be available and could improve both adherence and outcomes.
The largest unmet need for patients with GA has been an efficacious and safe therapy. Over time, patients with GA experience severe vision impairment and blindness, resulting in loss of independence and decreased quality of life. There are currently no approved treatments for GA. Therefore, pegcetacoplan has the potential to fulfill this unmet need, slow the progression of GA and maintain sight for millions of patients.
What hurdles might it need to overcome to reach blockbuster status?
Despite its potential first-to-market launch into an area of high unmet need, the uptake of pegcetacoplan might be tempered by the need for monthly or bimonthly intravitreal administration, especially since many patients with GA are asymptomatic and not experiencing notable vision loss. This dosing interval in addition to the lack of therapeutic benefit on patients’ visual acuity likely contributed to the relatively high treatment discontinuation rates seen in phase 2 and 3 trials for GA. It also remains to be seen if targeting the complement cascade in GA is efficacious and safe in the long term, following the failure of lampalizumab, a complement D factor inhibitor, in phase 3 trials and its discontinuation for GA. Pegcetacoplan will need to demonstrate long-term efficacy and safety to drive its uptake among retinal specialists and ophthalmologists. The complement inhibitor pipeline is crowded, and pegcetacoplan could face competition from numerous other competitors, including Zimura (complement C5 inhibitor, Iveric Bio, phase 3 for GA in the United States and Europe), danicopan (complement D factor inhibitor, Alexion Pharmaceuticals Inc and AstraZeneca, phase 2 for PNH and GA) and iptacoplan (oral complement B factor inhibitor, Novartis, phase 2 for PNH and GA).
“Pegcetacoplan and Zimura both seem to slow down the growth of lesions. They both seem to have effectiveness. They both seem to increase the risk of developing wet AMD, which is a big problem because if you have dry AMD and you suddenly develop wet AMD, you have to give two injections into the eye. It sounds very promising because we have nothing to offer to these patients. I think the drugs’ effects are not major effects. I think the studies have been done on very late disease, and therefore, it could be that we are using them perhaps too late. I’m not sure which of the two will be the first to get to the market, but the one that is first to the market will have a huge advantage.”
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