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Study in ASH Late-Breaking Abstracts session: Iptacopan Resolves Anemia in Phase III Trial for Paroxysmal Nocturnal Hemoglobinuria

LBA-2: Oral Monotherapy with Iptacopan, a Proximal Complement Inhibitor of Factor B, Has Superior Efficacy to Intravenous Terminal Complement Inhibition with Standard of Care Eculizumab or Ravulizumab and Favorable Safety in Patients with Paroxysmal Nocturnal Hemoglobinuria and Residual Anemia: Results from the Randomized, Active-Comparator-Controlled, Open-Label, Multicenter, Phase III Apply-PNH Study

The experimental oral medication iptacopan dramatically increased hemoglobin levels and reduced the need for blood transfusions among people with paroxysmal nocturnal hemoglobinuria (PNH) compared with the standard of care, according to the findings from a new phase III trial presented during the 64th American Society of Hematology (ASH) Annual Meeting and Exposition. At 24 weeks, almost all patients taking iptacopan saw an increase in hemoglobin (the protein that allows red blood cells to carry oxygen) of 2 grams per deciliter (g/dL) or higher without a blood transfusion, compared with zero patients in the standard of care arm.

PNH is a blood disease in which the immune system attacks blood cells, leading to severe anemia and fatigue as well as dangerous blood clots. It is a rare disease with about 10 to 20 cases per million people worldwide. If untreated, people with the condition face a high risk of death by early or mid-adulthood. In the past 15 years, intravenous monoclonal antibody treatments have significantly improved survival rates, although many patients experience residual anemia with available treatments. In the study, iptacopan boosted hemoglobin to nearly normal levels, while most patients receiving standard of care remained anemic.

“These results suggest iptacopan could be practice-changing for PNH and could essentially allow patients to live a normal life with just one pill each morning and night,” said Régis Peffault de Latour, MD, PhD, of Saint-Louis Hospital, Greater Paris University Hospitals. “This treatment represents a new class of agent that is not only more convenient, but offers a much better clinical response. It’s a huge step forward for treating this devastating disease.”

Iptacopan is designed to work through a different mechanism of action than existing therapies, interfering with a key biological cascade involved in PNH upstream of the mechanisms targeted by other medications. Researchers attribute the strength of the observed effect to the drug’s ability to stop this cascade early on, akin to closing a kind of (more effective) floodgate.

“The evidence suggests that this treatment is safe, and that it is simply better because of the biological pathway we are targeting, as predicted by robust preclinical observations,” Dr. Peffault de Latour said. “This means we can achieve better results without any increase in side effects or complications.”

The trial enrolled 97 people with PNH who experienced residual anemia despite treatment with standard of care medications eculizumab or ravulizumab. Approximately two-thirds of participants were randomly assigned to receive iptacopan and approximately one-third continued receiving their standard of care therapy. At 24 weeks, those taking iptacopan saw an average hemoglobin level increase of 3.59 g/dL, compared with an average decrease of 0.04 g/dL among those in the control arm. In addition, two-thirds of patients taking iptacopan and zero patients in the control arm achieved a hemoglobin level of 12 g/dL or higher without a blood transfusion; mean hemoglobin levels at 24 weeks irrespective of transfusions were 12.6 g/dL in those taking iptacopan and 9.2 g/dL in those on standard of care.

The need for blood transfusions was also markedly lower among patients taking iptacopan, with just two patients in the iptacopan arm and more than half of those in the control group requiring transfusions. Patients taking iptacopan also experienced significantly less fatigue. The most common adverse events related to iptacopan included headache and diarrhea. COVID-19 infections and breakthrough hemolysis were more common among those on standard of care regimens.

Researchers cautioned that these are early results, and more follow-up is needed to determine the long-term safety and efficacy.

Régis Peffault de Latour, Saint-Louis Hospital, Greater Paris University Hospitals, will present this study during an oral presentation on Tuesday, December 13, 2022, at 9:00 a.m. Central time in the Hall E.

Additional press briefings took place throughout the meeting on pediatric cancer care, advances in blood cancer research and care, novel drug development, and health equity. For the complete annual meeting program and abstracts visit www.hematology.org/annual-meeting. Follow ASH and #ASH22 on Twitter, Instagram, LinkedIn, and Facebook for the most up-to-date information about the 2022 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH’s flagship journal, Blood (www.bloodjournal.org), is the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), is the Society’s online, peer-reviewed open-access journal.


Leah Enser, ASH, [email protected]
Kira Sampson, ASH, [email protected]
Brianne Cannon, FleishmanHillard, [email protected]