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Chokri Ben Lamine: Cemdisiran in PNH – Why Combine Complement Therapies? 
Chokri Ben Lamine/LinkedIn
Sep 19, 2026, 01:23

Chokri Ben Lamine: Cemdisiran in PNH – Why Combine Complement Therapies? 

Chokri Ben Lamine, Hematologist at King Faisal Specialist Hospital and Research Center, shared a post on X:

“Cemdisiran in PNH: why combine complement therapies?

1.Mechanism

Cemdisiran is a GalNAc-conjugated small interfering RNA (siRNA) that silences hepatic C5 mRNA, leading to decreased C5 production and reduced terminal complement activity.

Despite more than 90% C5 reduction in early PNH studies, monotherapy did not adequately prevent hemolysis. Residual C5 activity matters!

Phase 1/2 study⁠

2.Cemdisiran with pozelimab

Two complementary mechanisms targeting C5:

  • Cemdisiran reduces C5 production.
  • Pozelimab blocks circulating C5.

The goal: sustained terminal complement suppression with less frequent dosing and fewer pharmacokinetic gaps.

Studied regimen: cemdisiran 200 mg SC with pozelimab 400 mg SC every 4 weeks. This is an investigational PNH regimen.

Phase 2 trial⁠

3.ACCESS-1: promising comparative data

Exploratory randomized cohort: 48 complement-inhibitor-naïve patients; combination versus ravulizumab.

Across weeks 8–26, average proportions achieving:

  • LDH less than or equal to 1.5 times ULN: 96% vs 80%
  • LDH normalization: 93% vs 65%

Small exploratory cohort: these results do not establish definitive superiority for thrombosis, survival or overall clinical benefit.

ACCESS-1 results, ASH 2024⁠

4.Cemdisiran with eculizumab

Early proof-of-concept work showed improved hemolysis control when eculizumab was added to cemdisiran.

Reducing the C5 pool may permit lower antibody exposure or longer intervals—but these findings do not justify empirically extending eculizumab dosing in routine practice.

Phase 1/2 study⁠

5.Dual C5 targeting has a biological limitation

Cemdisiran–pozelimab targets intravascular hemolysis.

Mechanistically, C3 opsonization can persist, leading to extravascular hemolysis (EVH). Therefore, LDH control does not guarantee Hb normalization. Persistent anemia also requires assessment for marrow failure and other causes.

Mechanism and residual anemia⁠

6.A different combination: danicopan with eculizumab or ravulizumab

Danicopan inhibits factor D, suppressing alternative-pathway amplification and C3-mediated EVH.

FDA-approved add-on for EVH in adults with PNH.

  • Start 150 mg orally TID; increase to 200 mg TID according to response.
  • Continue the C5 inhibitor: danicopan is not established as monotherapy.
  • Monitor liver enzymes, lipids and drug interactions.

FDA prescribing information⁠

7.Complement inhibition requires infection prevention

  • MenACWY with MenB vaccination, ideally completed ot updated 2 weeks or more before treatment.
  • Provide antibacterial prophylaxis when urgent initiation precedes adequate vaccination; consider ongoing prophylaxis according to protocol.
  • Vaccination does not eliminate meningococcal risk—fever or meningitic symptoms require immediate assessment.

CDC guidance⁠

8.Clinical distinction

  • Cemdisiran with anti-C5 antibody provides deeper, durable terminal blockade.
  • Danicopan with anti-C5 antibody provides proximal and terminal blockade to address EVH.

Cemdisiran combinations remain investigational for PNH. Its 2026 regulatory submission concerns generalized myasthenia gravis; this does not establish a PNH indication.

Regulatory update⁠”

Other posts featuring Chokri Ben Lamine on Hemostasis Today.

antibacterial prophylaxis Blood C3 opsonization Cemdisiran Chokri Ben Lamine Danicopan eculizumab EVH extravascular hemolysis Factor D GalNAc Hb Health Hematology hemolysis Hemostasis Hemostasis News Hemostasis Today hepatic C5 mRNA LDH Medicine myasthenia gravis PNH pozelimab Ravulizumab siRNA thrombosis
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