Oral therapy iptacopan eases anemia in CAD patients: Small trial
Meaningful improvements seen in markers of red blood cell destruction
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The oral medication iptacopan — approved for certain blood and complement-related conditions — helped alleviate anemia in most people with cold agglutinin disease (CAD) in a small Phase 2 clinical trial, according to study.
The complement cascade is a component of the immune system that contributes to the hemolysis, or destruction of red blood cells, that characterizes CAD.
“In this phase 2 … trial, iptacopan … showed encouraging efficacy in patients with CAD, with clinically meaningful improvements in hemoglobin, markers of hemolysis, and health-related quality of life,” researchers wrote.
They stressed, however, that larger studies are needed to further evaluate the safety and efficacy of iptacopan in people with CAD.
The trial results were described in the study, “Iptacopan for Immune Thrombocytopenia and Cold Agglutinin Disease: A Global Phase 2 Basket Clinical Trial,” published in the American Journal of Hematology.
The work was funded by Novartis, which markets iptacopan in the U.S. under the name Fabhalta to treat several disorders that are marked by abnormal activation of the immune complement cascade.
Iptacopan designed to block key complement factor
CAD is an autoimmune disorder marked by self-reactive antibodies that attack red blood cells at low temperatures. This leads to hemolysis and symptoms such as fatigue and anemia, or low levels of red blood cells or hemoglobin, the protein that red blood cells use to carry oxygen throughout the bloodstream.
When these abnormal antibodies bind to red blood cells, they activate the complement cascade, coating the cells with a complement protein called C3b that tags them for destruction.
Iptacopan is an oral therapy designed to block complement factor B, which helps prevent the formation of C3b. By suppressing this step, it can also prevent hemolysis, thereby representing a potential therapy for CAD.
Novartis launched a proof-of-concept Phase 2 clinical trial (NCT05086744) to test the therapy in adults with CAD or immune thrombocytopenia (ITP), an autoimmune disorder marked by self-reactive antibodies that attack platelets, or the cell fragments that help blood clot.
The multicenter study, conducted in the U.S., Europe, and Asia, involved 10 CAD patients and nine ITP patients. All participants were given 200 mg of iptacopan, administered twice daily, for 12 weeks, or aboutthree months.
Results from the CAD group showed that half of these participants experienced an increase in hemoglobin levels of at least 1.5 g/dL that was sustained for at least two weeks without any additional treatment — meeting the study’s main goal.
In addition to these five responders, a sixth patient experienced a similar increase in hemoglobin levels. However, this individual received a blood transfusion during the first days of the study and was therefore not considered a responder.
Overall, treatment was associated with an increase in hemoglobin levels and a reduction in the levels of hemolysis markers.
CAD patients reported improvements in measure of quality of life
Eight of the CAD patients — the five responders, plus three who were judged by their doctors to be benefiting from the treatment — entered into the study’s second part, where they received iptacopan treatment for a median of 11 months.
There was a gap between the two parts of the trial, of about a week on average, and during this time, patients’ hemoglobin levels “dropped rapidly,” the researchers wrote. However, once participants resumed iptacopan treatment, hemoglobin levels increased and generally remained stable with long-term therapy.
Reductions in hemolysis markers were also maintained in the study’s second part for most patients.
People with CAD also reported clinically meaningful improvements in the FACIT-Fatigue scale, a standardized assessment of self-reported fatigue that’s used as a proxy for quality of life.
We found that the prespecified criteria for positive efficacy were met in the CAD [group], but not in the ITP [group].
Specifically, scores increased by a mean of 8.8 points after three months of iptacopan treatment, reflecting less fatigue and improved quality of life. These benefits were sustained for most patients with long-term treatment.
Two people with CAD received a blood transfusion during the study’s second part, with one continuing with iptacopan and the other discontinuing the therapy due to lack of efficacy.
Safety data were in line with the therapy’s known profile, and no serious adverse events related to iptacopan were reported.
In contrast to the promising results seen in CAD, iptacopan led to essentially no benefit in people with ITP.
“We found that the prespecified criteria for positive efficacy were met in the CAD [group], but not in the ITP [group],” the researchers wrote. “The positive results in CAD are consistent with complement serving as the central [disease-causing] mechanism of red cell destruction in CAD. The results seen in patients with CAD are encouraging but require confirmation in a larger study.”
