FDA approves therapy for pediatric patients with serious rare blood disease

FDA has approved Ultomiris (ravulizumab-cwvz) injection to treat patients aged one month and older with paroxysmal nocturnal hemoglobinuria (PNH), a rare, life-threatening blood disease.

PNH is characterized by red blood cell destruction, anemia (red blood cells unable to carry enough oxygen to tissues), blood clots, and impaired bone marrow function (not making enough blood cells). The disease affects 1-1.5 people per million. Approximately 10% of cases are among pediatric patients. PNH can be serious, with median survival of 10 years after diagnosis. However, some patients live for decades with only minor symptoms.

PNH is caused by gene mutations that affect red blood cells. Red blood cells in people with these mutations are defective and can be destroyed by the immune system, which causes anemia.

The effectiveness of Ultomiris was evaluated in a 26-week study enrolling 13 pediatric patients aged 9-17 years with PNH. Five of the 13 patients had never been treated with complement inhibitors and eight patients had been treated with eculizumab, another PNH therapy. Patients received a first dose of Ultomiris and a maintenance treatment after 15 days. Then, patients weighing 20 kg (44 lbs) or more received treatment every eight weeks while patients weighing less than 20 kg received treatment every four weeks.

The primary endpoints for this study were pharmacokinetic (movement of the drug within the body) and pharmacodynamic (biochemical and physiologic effects of the drug) parameters. There were several secondary endpoints, including avoiding blood transfusions. After the 26-week study, 60% of patients who had not previously received complement inhibitors avoided a transfusion and all patients who had received prior eculizumab treatment avoided a transfusion.

Ultomiris is available only through a restricted program under a risk evaluation and mitigation strategy. Meningococcal (a type of bacteria) infections/sepsis can occur in patients taking Ultomiris and can become life-threatening or fatal if not recognized and treated early. Patients with unresolved Neisseria Meningitidis infection or who are not vaccinated against this infection should not take Ultomiris unless the risks of delaying treatment outweigh the risks of developing a meningococcal infection. Other infections can occur as well. Patients also should be monitored for infusion-related reactions. The effect of withdrawal of anticoagulant therapy during Ultomiris treatment has not been established. The most common side effects of Ultomiris for patients with PNH are upper respiratory tract infection and headache.

Ultomiris received priority review and orphan drug designation for the pediatric PNH indication.

Ultomiris was originally approved in 2018 and is also indicated to treat adults with PNH and adult and pediatric patients with atypical hemolytic uremic syndrome.