The US Food and Drug Administration (FDA) has approved ravulizumab (Ultomiris, Alexion Pharmaceuticals) to inhibit complement-mediated thrombotic microangiopathy (TMA) in adults and children age 1 month or older with atypical hemolytic uremic syndrome (aHUS), an ultra-rare blood disease.
This is the first pediatric approval for the long-acting C5 complement inhibitor.
In 2018, the FDA approved ravulizumab for adults with paroxysmal nocturnal hemoglobinuria (PNH), another rare blood disorder, as reported by Medscape Medical News.
Ravulizumab Has Longer Half-Life Than Existing Treatment
Atypical HUS is extremely rare and affects both children and adults. Many patients present in a critical condition, often requiring supportive care, including dialysis, in an intensive care unit. The prognosis of aHUS can be poor in many cases, so a timely and accurate diagnosis — in addition to treatment — is critical to improving patient outcomes.
The disease is characterized by inflammation and TMA mediated by chronic, uncontrolled activation of the complement system, which is part of the body's immune system.
This leads to microthrombi in various small blood vessels of the body, which can reduce or prevent proper blood flow to various organs (notably the kidney), leading to potentially irreversible damage, sudden or progressive kidney failure, and early death. It's estimated to affect 1 in 500,000 people in the US.
Eculizumab (Soliris, Alexion Pharmaceuticals) is also a C5 inhibitor approved for aHUS in adults in the US and EU since 2011, but ravulizumab has a half-life that is three to four times longer than that of eculizumab.
The FDA approved ravulizumab for aHUS based on data from two single-arm, open-label studies, one in adults and one in children. The pediatric study is ongoing and a total of 14 out of 16 children were enrolled and included in the interim analysis.
Ravulizumab is administered intravenously every 8 weeks (or every 4 weeks for pediatric patients weighing less than 20 kg), following a loading dose.
Efficacy evaluation of complete TMA response was defined by hematologic normalization parameters (platelet count and lactate dehydrogenase) and improved kidney function (as measured by ≥ 25% improvement in serum creatinine from baseline.
At 26 weeks, complete TMA response was achieved in 54% of adults and 71% of children (interim data on 14 of 16 children) treated with ravulizumab, the company said.
Treatment with ravulizumab also resulted in reduced thrombocytopenia (low blood platelet count) in 84% of adults and 93% of children, reduced hemolysis (destruction of red blood cells) in 77% of adults and 86% of children, and improved kidney function in 59% of adults and 79% of children.
"Clinical study results showed adult and pediatric patients had complete C5 inhibition following the first dose of ravulizumab. C5 inhibition was sustained over time with only six or seven infusions a year in adults — and that is important to consider for my patients," commented Spero Cataland, MD, professor of clinical internal medicine at Ohio State University College of Medicine's Wexner Medical Center, in a press release issued by Alexion.
The most common side effects were upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension, and pyrexia (fever).
Boxed Warning on Meningococcal Infection, Only Available With REMS
Ravulizumab includes a boxed warning about the risk of life-threatening meningococcal infections and sepsis. Patients should be immunized with meningococcal vaccines at least 2 weeks prior to administering the first dose of ravulizumab, unless the risks of delaying treatment outweigh the risks of developing a meningococcal infection. Vaccination reduces, but does not eliminate, the risk of meningococcal infection, the FDA said, and patients should be monitored for early signs of meningococcal infections and evaluated immediately if infection is suspected.
Ravulizumab is available only in conjunction with a Risk Evaluation and Mitigation Strategy (REMS) program and must be given with a patient medication guide that describes the drug's uses and risks. Full prescribing information is available online.
Cite this: FDA Clears Ravulizumab for Atypical Hemolytic Uremic Syndrome - Medscape - Oct 21, 2019.