PNH treatment Fabhalta resolved extravascular hemolysis: Report
Woman's hemoglobin levels increased; immature red blood cells declined
A 43-year-old woman with paroxysmal nocturnal hemoglobinuria (PNH) who experienced extravascular hemolysis — which occurs when red blood cells are destroyed or broken down outside of the blood vessels — despite previous treatment saw her condition significantly improve after initiating treatment with Fabhalta (iptacopan), according to a case report.
Fabhalta increased the levels of hemoglobin, the protein that carries oxygen in red blood cells, while reducing the count of immature red blood cells, known as reticulocytes. Both low levels of hemoglobin and high reticulocyte number are indicative of hemolysis.
The report, “Resolution of extravascular hemolysis with oral iptacopan monotherapy in a patient with treatment experienced paroxysmal nocturnal hemoglobinuria (PNH),” was published in The Central European Journal of Medicine.
PNH is characterized by red blood cell destruction, called hemolysis, occurring both inside (intravascular) and outside (extravascular) blood vessels, mainly in the liver and spleen. This destruction is caused by an abnormal activation of the complement cascade, a part of the immune system. The underlying cause of this red blood cell destruction is the abnormal activation of the complement cascade, a part of the immune system.
Treatment targets
Intravascular hemolysis involves the complement protein C5, which can be targeted by therapies such as Soliris (eculizumab) and Ultomiris (ravulizumab). On the other hand, extravascular hemolysis is linked to C3, a protein positioned upstream of C5 in the complement cascade.
Fabhalta, which is approved for PNH patients in the U.S., works by suppressing factor B, a protein of the complement system that is involved in C3 activation, which ultimately leads to C5 activation. The therapy is designed to prevent both intra- and extravascular hemolysis.
Researchers at the Medical University of Vienna, Austria, described the case of a woman with PNH previously treated with Ultomiris who participated in trials investigating BXC9930, an experimental therapy for PNH. After the trial was discontinued, she resumed treatment with Ultomiris. However, she continued to experience persistent anemia, characterized by low levels of red blood cells and hemoglobin.
Further analysis indicated that she probably had extravascular hemolysis. She began taking Fabhalta under an individually managed access program at an oral dose of 200 mg, twice daily. This new therapeutic intervention was initiated 41 days after her last dose of Ultomiris. She was vaccinated against infections by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenza.
After three weeks of treatment with Fabhalta, the patient saw an improvement in her hemoglobin levels, which increased to within the normal range. Her reticulocyte count decreased to normal levels within two weeks.
The patient’s haptoglobin levels remained undetectable both before and after the initiation of Fabhalta treatment. Haptoglobin is a protein that binds to free hemoglobin, and its levels are typically decreased in disorders associated with red blood cell destruction, such as anemia.
The patient’s fatigue, a common symptom of PNH, was comparable to healthy subjects, both before and after initiating treatment.
Following a peak at four weeks, hemoglobin levels slightly decreased, while reticulocyte counts increased, possibly indicating mild hemolysis. Since the patient was receiving regular blood transfusions before starting Fabhalta, she had a moderate increase in the levels of ferritin, an iron-binding protein, at baseline, which decreased within one week of treatment.
After about four months of treatment, the woman’s levels of hemoglobin and reticulocytes remained within the normal range, while fatigue levels remained stable.
The woman tolerated Fabhalta well. Adverse effects included chills without fever, mild muscle pain, and minor flush symptoms, which subsided during follow-up. No episodes of reoccurring hemolysis or infections were recorded.
“Together, [Fabhalta] monotherapy has the potential to normalize hemoglobin levels and reticulocyte counts in PNH patients with [extravascular hemolysis],” the researchers wrote.
About the Author
