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.

About pegcetacoplan

  1. Apellis Pharmaceuticals Inc.
  2. Complement C3 inhibitor
  3. Twice-weekly subcutaneous infusion via pump to treat PNH
  4. Monthly or every-other-month intravitreal administration to treat GA secondary to AMD
  5. Also being investigated for immune complex membranoproliferative glomerulonephritis (IC-MPGN), C3 glomerulopathy (C3G), amyotrophic lateral sclerosis (ALS), cold agglutinin disease (CAD) and hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA)
  6. 2.0 cases per 100,000 people: prevalence of PNH in the G7 markets in 2021
  7. ~2.3 million cases of GA in the G7 markets in 2021

Why is it a drug to watch?

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:

  1. Phase 2 FILLY: significantly slowed GA progression at 18 months
  2. Phase 3 OAKS and DERBY trials:
    • Monthly and bimonthly administrations reduced lesion growth from baseline (OAKS: 22% and 18%; DERBY: 19% and 16%, respectively) at 24 months compared with sham treatment, suggesting an accelerated effect over the treatment duration, which could encourage treatment adherence in the absence of visual acuity improvements
    • Reduction in GA lesion growth regardless of distance from the fovea, which could lead to a more inclusive label than Zimura (Iveric Bio; tested only in extrafoveal lesions)
    • Favorable safety for 11,757 injections over 24 months (0.034% rate of endophthalmitis/injection; 0.24% rate of intraocular inflammation/injection), with no reported cases of occlusive vasculitis or retinitis
  3. Pending data from the three-year open label extension study, GALE, may demonstrate long-term safety, an improved treatment effect and favorable functional data.

Review and approval status

May 2021:
For adults with PNH:
• Approval: U.S. FDA

December 2021:
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:
July 2018:
• Priority Review designation: U.S. FDA

July 2022:
• Fast track designation: U.S. FDA

December 2022:
• Anticipated submission for marketing authorization: European Medicines Agency (EMA)

February 2023:
• 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?

  1. With the aging population across the major markets, the prevalence of GA is expected to continue increasing, and the launch of pegcetacoplan and of Zimura could lead to increased GA diagnoses.
  2. The promising results from the phase 3 trials bode well for the mechanism of action and could pave the way for other complement system inhibitors to make it to market.
  3. There are no therapies currently approved for the treatment of GA, and there is substantial unmet need.
  4. The majority of sales will likely result from the intravitreal formulation for GA.
  5. Moderate uptake is expected upon launch, balanced between the approval based on slowing of GA progression and the lack of efficacy for visual acuity improvement, a more meaningful endpoint for quality of life.
  6. Pegcetacoplan is poised to be the first therapy approved for GA, providing a first-to-market advantage over Zimura, which is expected to launch a full year after pegcetacoplan.
  7. Pegcetacoplan is forecasted to have 76% of overall complement system inhibitor market share in the United States and Europe in 2027.

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).

expected sales in 2027 for GA
probability of success for pegcetacoplan for GA in the United States.

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