PMID- 37707673
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20240429
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Print)
IS  - 0741-238X (Linking)
VI  - 40
IP  - 11
DP  - 2023 Nov
TI  - Injection Site Reactions with Long-Term Pegcetacoplan Use in Patients with 
      Paroxysmal Nocturnal Hemoglobinuria: A Brief Report.
PG  - 5115-5129
LID - 10.1007/s12325-023-02653-4 [doi]
AB  - INTRODUCTION: Pegcetacoplan is a targeted complement component 3 (C3) therapy 
      approved for adults with paroxysmal nocturnal hemoglobinuria (PNH; US) or PNH 
      plus anemia despite C5-targeted therapy for >/= 3 months (EU). Patients with PNH 
      receiving pegcetacoplan in the phase 3 PEGASUS trial who experienced injection 
      site reactions (ISRs) mostly experienced mild events. We evaluated ISR incidence 
      and severity with longer-term treatment in the PEGASUS cohort of the Study 307 
      open-label extension (307 OLE). METHODS: Patients from PEGASUS enrolled in the 
      307 OLE continued pegcetacoplan subcutaneous self-administration twice or three 
      times weekly or every 3 days for an additional 48 weeks. ISRs were coded as 
      adverse events (AEs) or treatment-emergent AEs (TEAEs) and summarized by MedDRA 
      System Organ Class and Preferred Term. RESULTS: As of August 27, 2021, 58/64 
      patients from PEGASUS completed an additional 48 weeks of treatment in the 307 
      OLE (median treatment duration 337.0 [range 55-344] days); 95.3% (61/64) of 
      patients achieved compliance >/= 80%. ISRs occurred in 9/64 (14.1%) patients in the 
      307 OLE, which was lower than observed at PEGASUS completion (20/77; 26.0%). Most 
      patients with ISRs in the 307 OLE had events with a maximum severity of mild (7/9 
      patients; 77.8%). Injection site erythema and induration were the most common 
      overall (4/64 patients each; 6.3%) and pegcetacoplan-related (3/64 patients each; 
      4.7%) ISRs. The exposure-adjusted rates of these events were each 6.5 per 100 
      patient-years. No ISRs were classified as severe or serious TEAEs or led to drug 
      discontinuation. CONCLUSION: Though ISRs were common, most were mild, and the 
      percentage of patients reporting ISRs declined from PEGASUS through the 307 OLE. 
      Patient compliance remained high, and no patients discontinued because of ISRs, 
      suggesting that ISRs do not pose a barrier to long-term pegcetacoplan treatment. 
      TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03500549 (PEGASUS) and 
      NCT03531255 (307 OLE).
CI  - (c) 2023. The Author(s).
FAU - Sharma, Vivek
AU  - Sharma V
AUID- ORCID: 0000-0003-4871-2114
AD  - University of Louisville, Louisville, KY, USA. vivek.sharma@louisville.edu.
FAU - Koprivnikar, Jamie
AU  - Koprivnikar J
AD  - John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, 
      NJ, USA.
FAU - Drago, Kristen
AU  - Drago K
AD  - Apellis Pharmaceuticals, Inc, Waltham, MA, USA.
FAU - Savage, Jessica
AU  - Savage J
AD  - Apellis Pharmaceuticals, Inc, Waltham, MA, USA.
FAU - Bachelor, Allison
AU  - Bachelor A
AD  - Apellis Pharmaceuticals, Inc, Waltham, MA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03500549
SI  - ClinicalTrials.gov/NCT03531255
GR  - Apellis Pharmaceuticals/
GR  - Swedish Orphan Biovitrum/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230914
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - TO3JYR3BOU (pegcetacoplan)
MH  - Adult
MH  - Humans
MH  - *Hemoglobinuria, Paroxysmal/drug therapy
MH  - Injection Site Reaction
PMC - PMC10567944
OTO - NOTNLM
OT  - Clinical trial
OT  - Injection site reactions
OT  - Management
OT  - Paroxysmal nocturnal hemoglobinuria
OT  - Pegcetacoplan
COIS- KD, JS, and AB are employees of Apellis Pharmaceuticals, Inc and hold stock 
      options. VS is on the speaker's bureau for Alexion, Sanofi, and Novo Nordisk. JK: 
      is on the advisory board/consultant for Apellis, Novartis and Alexion, and is on 
      the speaker's bureau for Alexion, Apellis, Amgen, Jazz, CTI, BMS, and AbbVie.
EDAT- 2023/09/14 12:42
MHDA- 2023/11/27 12:42
PMCR- 2023/09/14
CRDT- 2023/09/14 11:11
PHST- 2023/07/06 00:00 [received]
PHST- 2023/08/16 00:00 [accepted]
PHST- 2023/11/27 12:42 [medline]
PHST- 2023/09/14 12:42 [pubmed]
PHST- 2023/09/14 11:11 [entrez]
PHST- 2023/09/14 00:00 [pmc-release]
AID - 10.1007/s12325-023-02653-4 [pii]
AID - 2653 [pii]
AID - 10.1007/s12325-023-02653-4 [doi]
PST - ppublish
SO  - Adv Ther. 2023 Nov;40(11):5115-5129. doi: 10.1007/s12325-023-02653-4. Epub 2023 
      Sep 14.