Biogen completes acquisition of Apellis Pharmaceuticals

The ownership of pegcetacoplan intravitreal injection (SYFOVRE; Apellis Pharmaceuticals), the approved treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD), has changed hands. Biogen Inc. announced it has completed its acquisition of Apellis Pharmaceuticals Inc., making Apellis a wholly owned subsidiary and absorbing SYFOVRE into what is now an expanded immunology and complement-focused commercial portfolio.¹ For retina specialists managing patients with GA, the near-term clinical implications of the transaction are limited, but the shift in stewardship over the compound's lifecycle development and commercialization carries potential longer-term significance—particularly around formulation innovation, access infrastructure, and ongoing pharmacovigilance.

The deal, valued at approximately $5.6 billion in upfront equity consideration, was first announced on March 31, 2026, and closed after approximately 82.4% of outstanding Apellis shares were tendered by the May 13 offer deadline.¹ The transaction also incorporates a contingent value right (CVR) instrument—up to $4 per share in milestone-based payments tied to future SYFOVRE global net sales performance—underscoring the commercial expectations that Biogen has placed on the GA market.¹ For physicians, the corporate mechanics are secondary; the more clinically pertinent question is what continued development of SYFOVRE and its complement-inhibiting platform will mean for patients with this progressive retinal disease.

SYFOVRE and geographic atrophy: clinical background

Geographic atrophy is a late-stage manifestation of nonexudative AMD characterized by the progressive, irreversible loss of retinal pigment epithelium, photoreceptors, and the underlying choriocapillaris.²,³ Approximately 1 million people in the United States and 5 million to 8 million individuals globally are estimated to have GA in at least one eye.³,⁴ The disease disproportionately affects older adults, with prevalence increasing sharply after age 65, and accounts for roughly 20% of legal blindness in North America.⁴ Affected patients experience gradual deterioration of central vision, impairing the ability to read, recognize faces, and drive—often with little warning of early-stage lesion growth.

Prior to February 2023, no pharmacological treatment had been approved for GA; clinicians were limited to monitoring, low vision rehabilitation, and counseling patients on modifiable risk factors. The FDA approval of intravitreal pegcetacoplan on February 17, 2023, marked the first time any agent had received regulatory clearance specifically for this indication in the United States.⁵ A second complement inhibitor, avacincaptad pegol (IZERVAY; Astellas Pharma), received FDA approval for the same indication in August 2023, providing clinicians with a second option; both agents represent a shared mechanistic class built on complement pathway inhibition.⁶

Mechanism of action and drug-class context

Pegcetacoplan is a pegylated cyclic peptide that inhibits complement component C3, acting at a convergence point upstream in the complement cascade shared by the classical, lectin, and alternative pathways.⁵,⁷ By binding C3 and its cleavage fragment C3b, the drug suppresses generation of downstream opsonins, anaphylatoxins, and membrane attack complex constituents implicated in the retinal cell death that characterizes GA progression. This broad complement suppression distinguishes C3-targeted agents such as pegcetacoplan from complement factor D or factor B inhibitors, which act more selectively on the alternative pathway.

Pegcetacoplan's systemic formulation (EMPAVELI; Apellis) had received prior FDA approval for paroxysmal nocturnal hemoglobinuria in May 2021 and subsequently for C3 glomerulopathy and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) in patients aged 12 and older.⁷ The intravitreal formulation for GA (SYFOVRE) is administered at a dose of 15 mg per 0.1 mL; dosing flexibility ranges from every 25 to 60 days, a practical consideration for patient adherence to an ongoing injection regimen.⁵

Pivotal trial evidence: OAKS and DERBY

The FDA approval of SYFOVRE rested primarily on 24-month data from 2 large, multinational, randomized, double-masked, sham-controlled phase 3 studies—OAKS (n = 637) and DERBY (n = 621)—enrolling patients aged 60 years and older with GA secondary to AMD.⁸ Patients were assigned in a 2:2:1:1 ratio to monthly pegcetacoplan, every-other-month (EOM) pegcetacoplan, or pooled sham, with the primary endpoint being change in total GA lesion area from baseline as measured by fundus autofluorescence at 12 months.⁸

In OAKS, both monthly and EOM dosing met the primary endpoint at 12 months, reducing GA lesion growth by 21% (monthly; absolute difference –0.41 mm², p=0.0004) and 16% (EOM; absolute difference –0.32 mm², p=0.0055) compared with sham.⁸ At 24 months, these reductions increased to 22% and 18%, respectively, in OAKS. In DERBY, neither dosing arm met the primary endpoint at 12 months, with reductions of approximately 12% (monthly) and 11% (EOM) that did not reach statistical significance; however, by 24 months, effects in DERBY converged toward those seen in OAKS, with monthly and EOM dosing showing 18% and 16% reductions versus sham, respectively.⁸

Critically, prespecified key secondary endpoints measuring visual function—including monocular maximum reading speed, best-corrected visual acuity, and functional reading independence—showed no statistically significant differences between active treatment and sham arms in either study at 24 months.⁸ This absence of a measurable functional benefit at the primary analysis period has remained a central point of discussion in the retina community when counseling patients about realistic treatment expectations.

Long-term follow-up data from the open-label extension study GALE—presented in mid-2024 and updated in late 2025—reported that 36-month analysis showed preserved visual function in a prespecified endpoint and that 5 years of continuous pegcetacoplan treatment was associated with a delay in GA lesion progression of approximately 1.5 years in patients with non-subfoveal lesions compared with historical sham.⁹ These extension data are hypothesis-generating, but their uncontrolled design limits causal interpretation.

Safety profile and postmarketing pharmacovigilance

The overall safety profile in the phase 3 trials was characterized predominantly by injection-related events. Intraocular inflammation (IOI) was observed in 2.1% (EOM) to 3.8% (monthly) of pegcetacoplan-treated patients at 24 months across both studies.⁸ Notably, no cases of retinal vasculitis were identified in the clinical trial populations.

A significant postmarketing safety signal emerged beginning in April 2023, shortly after commercial availability. The American Society of Retina Specialists (ASRS) Research and Safety in Therapeutics (ReST) Committee conducted a retrospective review that identified 14 eyes of 13 patients with confirmed retinal vasculitis, with occlusive retinal vasculopathy verified in 11 eyes (79%).¹⁰ Cases occurred a median of 10.5 days following the first pegcetacoplan injection. Outcomes were severe: a majority of affected eyes experienced more than a 3-line decrease in visual acuity, with 6 eyes losing more than 6 lines, and 2 eyes were subsequently enucleated.¹⁰ The etiology of this inflammatory response remains incompletely understood, and optimal management protocols are still being refined.

Following these postmarketing reports, the prescribing information for SYFOVRE was updated to include a specific warning regarding retinal vasculitis and retinal vascular occlusion. An additional, well-documented concern involves the increased incidence of new-onset neovascular AMD (nAMD) in treatment arms versus sham: approximately 11% to 13% (monthly dosing) and 6% to 8% (EOM) in treated patients at 24 months, compared with 2% to 4% in sham groups across OAKS and DERBY.⁸ Clinicians prescribing SYFOVRE are advised to monitor for signs of nAMD development, which may require concurrent or sequential anti-vascular endothelial growth factor (anti-VEGF) therapy.

Implications of the Biogen acquisition for retina specialists

From a near-term prescribing standpoint, the change in corporate ownership is not expected to alter clinical protocols, access pathways, or the current label. Apellis' commercial and medical infrastructure—including an established field force—will transition to Biogen, which has indicated plans to preserve continuity of commercial operations.¹

Several development-stage programs initiated under Apellis have forward-looking clinical relevance. A prefilled syringe formulation of SYFOVRE completed a clinical study under Apellis, with a regulatory submission to the FDA anticipated in the near term.¹¹ If approved, the device change could modestly affect injection workflow in clinical practice. Additionally, biomarker-driven patient selection strategies—aimed at identifying individuals most likely to derive benefit from complement inhibition—remain an active area of investigation, though no validated prospective selection tools have reached clinical practice.

The broader portfolio context is also pertinent. Biogen's pipeline includes felzartamab, an anti-CD38 monoclonal antibody in phase 3 development for antibody-mediated rejection in kidney transplant recipients, with a first readout expected in the first half of 2027.¹ While this program is outside ophthalmology, Apellis' established nephrology infrastructure—built partly around EMPAVELI's expanded kidney indications—is expected to accelerate Biogen's commercial readiness for felzartamab.¹ The broader complement franchise thus connects retinal and renal disease under a single scientific and commercial umbrella, a strategic consolidation whose downstream effects on resource allocation and complement research priorities remain to be seen.

References

1. Biogen Inc. Biogen completes acquisition of Apellis Pharmaceuticals. Press release. May 14, 2026. https://investors.biogen.com/news-releases/news-release-details/biogen-completes-acquisition-apellis-pharmaceuticals

2. Bhutto I, Lutty G. Understanding age-related macular degeneration (AMD): relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. Mol Aspects Med. 2012;33(4):295-317. doi:10.1016/j.mam.2012.04.005 https://pubmed.ncbi.nlm.nih.gov/22542780/

3. Lindblad AS, Lloyd PC, Clemons TE, et al. Change in area of geographic atrophy in the Age-Related Eye Disease Study: AREDS Report Number 26. Arch Ophthalmol. 2009;127(9):1168-1174. doi:10.1001/archophthalmol.2009.198 https://pubmed.ncbi.nlm.nih.gov/19752426/

4. Fleckenstein M, Schmitz-Valckenberg S, Martens C, et al. The pathophysiology of geographic atrophy secondary to age-related macular degeneration and the complement pathway as a therapeutic target. Retina. 2022;42(1):1-19. doi:10.1097/IAE.0000000000003270 https://journals.lww.com/retinajournal/Fulltext/2017/05000/THE_PATHOPHYSIOLOGY_OF_GEOGRAPHIC_ATROPHY.2.aspx

5. Apellis Pharmaceuticals Inc. FDA approves SYFOVRE™ (pegcetacoplan injection) as the first and only treatment for geographic atrophy. Press release. February 17, 2023. https://investors.apellis.com/news-releases/news-release-details/fda-approves-syfovretm-pegcetacoplan-injection-first-and-only

6. Khanani AM, Patel SS, Staurenghi G, et al. Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial. Lancet. 2023;402(10411):1449-1458. doi:10.1016/S0140-6736(23)01583-0 https://pubmed.ncbi.nlm.nih.gov/37837986/

7. SYFOVRE® (pegcetacoplan injection) [prescribing information]. Apellis Pharmaceuticals Inc.; February 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217171s000lbl.pdf

8. Lad EM, Boulanger-Scemama E, Francois C, et al. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials. Lancet. 2023;402(10411):1434-1448. doi:10.1016/S0140-6736(23)01520-9 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01520-9/abstract

9. Dhoot DS, Wykoff CC, Ou WC, et al. Pegcetacoplan preserves visual function at 36 months in patients with geographic atrophy: GALE long-term extension data [presented at Clinical Trials at the Summit]. June 2024. As reported by Ophthalmology Times: https://www.ophthalmologytimes.com/view/pegcetacoplan-injection-preserves-visual-function-at-36-weeks-in-patients-with-geographic-atrophy (Full peer-reviewed publication not confirmed at time of this article; link directs to conference news report.)

10. Witkin AJ, Hahn P, Murray TG, et al; ASRS Research and Safety in Therapeutics (ReST) Committee. Retinal vasculitis after intravitreal pegcetacoplan: report from the ASRS Research and Safety in Therapeutics (ReST) Committee. J VitreoRetinal Dis. 2023;7(6):465-472. doi:10.1177/24741264231212229 https://pmc.ncbi.nlm.nih.gov/articles/PMC10786078/

11. Biogen Inc. Biogen to acquire Apellis, enhancing the company's growth portfolio in immunology and rare disease. Press release. March 31, 2026. https://investors.biogen.com/news-releases/news-release-details/biogen-acquire-apellis-enhancing-companys-growth-portfolio