As of June 7, 2021, an injectable treatment is now available for patients aged 1 month+ with paroxysmal nocturnal hemoglobinuria. The FDA recently approved Ultomiris (ravulizumab-cwvz) for these patients. Previously, Ultomiris was approved for adults with PNH, and both adults and pediatric patients with atypical hemolytic uremic syndrome (aHUS). Now, the therapy will benefit pediatric patients with PNH moving forward.
According to drug developer Alexion Pharmaceuticals (“Alexion”), Ultomiris is:
the first and only long-acting C5 inhibitor administered every 8 weeks…in maintenance dosing, ULTOMIRIS works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system.
Researchers evaluated the safety, tolerability, and efficacy of Ultomiris in pediatric patients with PNH within a 26-week (6~ month) study. In this case, the patient ages ranged from 9 to 17. Altogether, 13 patients enrolled. Of these, 5 had previously never been treated with any form of complement inhibitors, while the remaining patients had been treated with eculizumab.
During the trial, patients received an initial dose followed by maintenance treatment 15 days later. Patients weighing over 44 pounds were given treatment every 8 weeks, while those under that weight were treated every 4 weeks. Ultimately, researchers determined that:
- 60% (3 patients) who had never been previously treated did not need a transfusion.
- Alternately, 100% (8 patients) who had been previously treated did not need a transfusion.
- While Ultomiris is relatively safe and well-tolerated, there are some safety considerations. For example, some patients may experience adverse reactions such as headaches, infusion site reactions, or upper respiratory tract infections.
Additionally, Ultomiris was granted Priority Review and Orphan Drug designations. Although the treatment is currently only available through a restricted program, it will possibly be more accessible in the future.
Paroxysmal Nocturnal Hemoglobinuria (PNH)
PIGA gene mutations cause paroxysmal nocturnal hemoglobinuria (PNH), an acquired hematopoietic stem cell (HSC) disorder. In this rare blood disease, these gene mutations cause the production of rapidly multiplying PNH cells, or defective blood cells. When the immune system attacks, it often attacks the stem cells, causing issues with blood cell production and hemolysis, or the breaking apart of red blood cells. The bone marrow fails to produce enough red or white blood cells or platelets. Altogether, this leads to a variety of health issues. For example, the condition is usually characterized by hemolytic anemia, blood clots, and poor bone marrow function.
In mild cases, patients may survive for decades after diagnosis. However, the typical survival rate following a PNH diagnosis is around 10 years. Both males and females are equally affected. Typically, PNH affects younger adults, with symptom onset appearing between ages 35-40. Additionally, around 30% of PNH cases result from aplastic anemia treatment.
- Significant fatigue or general malaise
- Chest or back pain
- Difficulty swallowing
- Frequent infections
- Easy bruising and bleeding
- Extremely pale skin
- Dark and/or bloody urine
- Sexual dysfunction
- Note: This specific symptom is typically found in males with PNH.
- Shortness of breath and/or difficulty breathing
- Severe headache
- Jaundice (yellowing of the skin and eyes)
- High heart rate
- Abdominal contractions
- Kidney disease