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IPIG 2025 | The role of ravulizumab in PNH and comparing this agent to eculizumab
Austin Kulasekararaj, MBBS, MD, MRCP, FRCPath, King’s College Hospital NHS Foundation Trust, London, UK, comments on the role of ravulizumab, a modified eculizumab, in the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). Dr Kulasekararaj highlights that ravulizumab offers a more convenient dosing schedule to eculizumab and has shown non-inferiority in clinical trials, while reducing the risk of pharmacokinetic breakthrough hemolysis. This interview took place at the 2nd International PNH Interest Group (IPIG) Conference in Paris, France.
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Transcript
Yes, so as PNH physicians we’ve been very much used to using C5 inhibition right from 2004 in clinical trials of using eculizumab, and subsequently, because it was two weekly infusions, there were issues from a patient perspective because two weekly is too frequent. So, ravulizumab in multiple clinical trials i.e., PNH 301 and 302, showed that ravulizumab, which is a modified eculizumab, can be given every eight weekly instead of every two weekly eculizumab and had a similar profile to eculizumab i...
Yes, so as PNH physicians we’ve been very much used to using C5 inhibition right from 2004 in clinical trials of using eculizumab, and subsequently, because it was two weekly infusions, there were issues from a patient perspective because two weekly is too frequent. So, ravulizumab in multiple clinical trials i.e., PNH 301 and 302, showed that ravulizumab, which is a modified eculizumab, can be given every eight weekly instead of every two weekly eculizumab and had a similar profile to eculizumab i.e, showed non-inferiority to eculizumab. It was fantastic for patient benefits as well, and also avoided this issue of pharmacokinetic breakthrough hemolysis, which was seen in eculizumab in 20 to 25 percent of patients. So it was definitely a step up from pre-existing eculizumab, and nowadays the standard of care C5 inhibition is mostly ravulizumab in countries with approval of this drug. So again it is very reassuring to note this long-term data which was up to six years that the benefits of ravulizumab in these patients were on clinical trial continued and persisted as compared to patients on the PNH registry and since it was six-year data, we could look at things like breakthrough, long-term survival, thrombosis risk as well, which was all very reassuring.
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Disclosures
Research support (to institution): Celgene/BMS, Novartis; Consultant: Samsung, Novo Nordisk, Alexion/AstraZeneca, Arrowhead Pharmaceuticals, Silence Therapeutics, AdaRx, Ono Pharma; Speaker’s fees: Alexion/AstraZeneca, Amgen, Celgene/BMS, Pfizer, Novartis, Ra Pharmaceuticals/UCB, Roche, Sobi, Janssen; Scientific advisory board/data monitoring committee: Alexion/Astra Zeneca, Apellis, Amgen, Agios, BioCryst, Celgene/BMS, Geron, Novartis, Pfizer, Regeneron, Roche, Sobi, Janssen, Samsung.
