Biogen to acquire Apellis in $5.6 billion deal

Biogen has announced a definitive agreement to acquire Apellis Pharmaceuticals for approximately $5.6 billion, a move that would expand its presence in complement-mediated diseases, including geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and rare renal disorders. The transaction, expected to close in the second quarter of 2026 pending regulatory approvals, would bring pegcetacoplan-based therapies into Biogen’s commercial portfolio.

For ophthalmologists and retina specialists, the acquisition is notable primarily for its implications around pegcetacoplan intravitreal therapy (SYFOVRE), one of the first approved treatments for GA, a late-stage manifestation of AMD characterized by progressive and irreversible retinal degeneration. The deal may influence long-term commercialization, access strategies, and ongoing development programs in a therapeutic area with limited treatment options.

Apellis’ portfolio includes 2 complement C3 inhibitors: pegcetacoplan for intravitreal use in GA and systemic pegcetacoplan (EMPAVELI) for hematologic and renal indications. Both agents target complement component 3, a central protein in the complement cascade implicated in inflammatory and degenerative processes across multiple organ systems.

Trial evidence and clinical data

SYFOVRE was approved by the US Food and Drug Administration (FDA) in 2023 based on results from the phase 3 OAKS and DERBY trials, which evaluated intravitreal pegcetacoplan in patients with GA secondary to AMD. In these randomized, sham-controlled studies, treatment reduced the rate of GA lesion growth compared with sham, with increasing treatment effect over time. At 24 months, monthly dosing demonstrated up to a 36% reduction in lesion growth in DERBY, while OAKS showed statistically significant reductions at earlier time points.¹,²

However, the magnitude of benefit has been interpreted cautiously in clinical practice, given the absence of demonstrated improvement in visual acuity and the modest absolute differences in lesion progression. Additionally, postmarketing safety signals—including reports of intraocular inflammation and rare cases of occlusive retinal vasculitis—have prompted ongoing pharmacovigilance and updates to prescribing information.³

Long-term data from the GALE open-label extension study suggest a sustained effect on lesion growth over several years, although these findings are based on post hoc analyses and nonrandomized comparisons, limiting interpretability.

EMPAVELI (systemic pegcetacoplan) has also demonstrated efficacy in complement-mediated renal disease. In the phase 3 VALIANT study, pegcetacoplan reduced proteinuria and stabilized kidney function in patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), rare conditions with limited approved therapies. At present, full peer-reviewed publication of VALIANT results remains limited, and detailed efficacy and safety outcomes should be interpreted in that context.

Clinical context

Geographic atrophy affects an estimated 1 million individuals in the United States and represents a major cause of irreversible vision loss in older adults. Until recently, management was limited to supportive care, including low-vision rehabilitation and risk factor modification. The introduction of complement inhibitors such as pegcetacoplan and avacincaptad pegol has marked a shift toward disease-modifying approaches, although treatment burden and safety considerations remain key challenges.⁴

Complement dysregulation has also been implicated in a range of systemic diseases, including paroxysmal nocturnal hemoglobinuria (PNH) and C3G, supporting the broader therapeutic rationale for C3 inhibition. Pegcetacoplan’s mechanism—targeting C3 upstream in the cascade—differs from C5 inhibitors such as eculizumab, potentially offering broader complement suppression but also raising theoretical risks related to infection and immune modulation.

Strategic and clinical implications

From a clinical perspective, the acquisition is unlikely to immediately alter prescribing patterns but may affect future development pathways, including device innovations such as prefilled syringes and potential label expansions. Biogen’s existing infrastructure in neurology and immunology could also shape lifecycle management strategies for pegcetacoplan across indications.

Nevertheless, uncertainties remain. The long-term safety profile of intravitreal complement inhibition continues to be defined, and real-world effectiveness data are still emerging. Additionally, cost, injection frequency, and patient selection criteria remain areas of active discussion within the retina community.

Limitations and next steps

Key limitations in the available evidence include the modest effect size observed in GA trials, lack of visual acuity benefit, and reliance on surrogate endpoints such as lesion growth. For renal indications, peer-reviewed data are still limited for some late-stage trials, underscoring the need for full publication and independent validation.

Future research directions include head-to-head comparisons among complement inhibitors, optimization of dosing intervals, and identification of biomarkers to guide treatment selection. Regulatory review of additional delivery formats, such as prefilled syringes, is anticipated.

References

1. Liao DS, Grossi FV, El Mehdi D, et al. Complement C3 inhibitor pegcetacoplan for geographic atrophy secondary to age-related macular degeneration: results from the OAKS and DERBY trials. Ophthalmology. 2023. https://doi.org/10.1016/j.ophtha.2023.03.001

2. ClinicalTrials.gov. Study of intravitreal APL-2 therapy in patients with geographic atrophy (DERBY). https://clinicaltrials.gov/study/NCT03525600

3. US Food and Drug Administration. SYFOVRE (pegcetacoplan injection) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217171s000lbl.pdf

4. Fleckenstein M, Mitchell P, Freund KB, et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125(3):369-390. https://doi.org/10.1016/j.ophtha.2017.08.038