Evidence review: Open Peptide Project (verified against primary PubMed, ClinicalTrials.gov & FDA records) · Last checked 2026-10-27. ← Back to Evidence Library

Pegcetacoplan (Empaveli, Syfovre, APL-2): what the evidence says

Name: Pegcetacoplan (Empaveli, Syfovre, APL-2)
Published: 2026-10-27

At a glance

What it is: a pegylated synthetic peptide that blocks complement protein C3. Injected under the skin as Empaveli (approved May 2021) for PNH and, per the current label, C3 glomerulopathy and IC-MPGN; injected into the eye as Syfovre (approved Feb 2023) for geographic atrophy. ^{R1, R2, R3, R4}

What the evidence says: Human in the PEGASUS phase 3 trial (80 adults with PNH), pegcetacoplan raised hemoglobin more than eculizumab, and 85% vs 15% no longer needed transfusions. ^R5

Biggest risks: boxed warning for life-threatening infections from encapsulated bacteria; available only through a REMS program. ^R3 Syfovre carries warnings for endophthalmitis, retinal vasculitis and retinal vascular occlusion. ^R4

Rating


Human Human evidence	Strong: PEGASUS RCT (n = 80) ^R5
Animal Animal / lab evidence	Not reviewed
Regulatory	FDA-approved ^R1 · not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page ^{R6, R7, R8} · not named by WADA ^R9
Established human dose	Yes, label dose (see Study details)

Evidence verdict: PNH: Strong (phase 3 RCT vs eculizumab) · Geographic atrophy: approved (trials not reviewed here)

This page reports what studies used. It is not dosing advice.

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

About the evidence: PEGASUS was open-label but used objective blood measures. The eye indication's trials were not reviewed for this page. UNVERIFIED geographic-atrophy trial results.

What is it?

Related pages: romiplostim, etelcalcetide.

Does it work?

Human PEGASUS: hemoglobin +3.84 g/dL vs eculizumab at 16 weeks. ^R5

Is it safe?

Human Injection-site reactions 37% and diarrhea 22%; no meningitis in the trial. ^R5
Boxed warning and REMS. ^R3

Gray-market vials: extra risks

A gray-market vial has no quality control and no guarantee of identity, strength or sterility. We test retail vials blind under the Open Peptide Standard; see /tests/. A passing test covers one batch on one date and does not mean the compound is safe.

Is it legal?

US: FDA-approved, prescription (Empaveli, Syfovre). ^{R1, R2}
Compounding: not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page. ^{R6, R7, R8}
Sport: not named on WADA's 2026 Prohibited List. ^R9

Study details

These are amounts researchers used, not recommendations.

Study	People / model	Route	Amount used	Follow-up	Reported	Citation
PEGASUS 2021	80 adults with PNH	SC	Per label/study	16 weeks	Hemoglobin +3.84 g/dL vs eculizumab	PMID 33730455

Full reference list (PubMed, CT.gov, FDA and WADA checked Oct 27, 2026)

^R1 Drugs@FDA, Empaveli (pegcetacoplan), application NDA215014 (openFDA drugsfda record checked Oct 27, 2026). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=NDA215014
^R2 Drugs@FDA, Syfovre (pegcetacoplan intravitreal), application NDA217171 (openFDA drugsfda record checked Oct 27, 2026). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=NDA217171
^R3 Empaveli prescribing information, label published Aug 21, 2026 (DailyMed, checked Oct 27, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c23d89e9-b00b-4520-e053-2995a90a95af
^R4 Syfovre prescribing information, label published Sep 16, 2025 (DailyMed, checked Oct 27, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b4434e61-9ec9-4e0e-bd60-45aaa0a87e64
^R5 Hillmen P, et al. N Engl J Med. 2021. PMID 33730455
^R6 FDA, 503A bulk drug substances categories list (updated May 14, 2026). https://www.fda.gov/media/94155/download
^R7 FDA, 503B bulk drug substances categories list (updated Mar 21, 2025). https://www.fda.gov/media/94164/download
^R8 FDA, Certain bulk drug substances for use in compounding that may present significant safety risks (content current Apr 22, 2026). https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
^R9 WADA. The 2026 Prohibited List, full list checked; compound not named. https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf

Disclaimer

This page is for education and harm reduction, not medical advice or a recommendation to use Pegcetacoplan (Empaveli, Syfovre, APL-2). This is a prescription medicine. Use it only under the care of a licensed clinician; do not buy it from research-chemical or gray-market sellers. Report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).