Currently Enrolling Trials
Ultomiris (ravulizumab-cwvz) is a humanized monoclonal antibody.
Ultomiris is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria.
Ultomiris is supplied as an injection for intravenous administration. Due to the risk of meningococcal infections/sepsis associated with the use of Ultomiris, patients should be vaccinated for meningococcal disease according to current ACIP guidelines to reduce the risk of serious infection. Provide two weeks of antibacterial drug prophylaxis to patients if Ultomiris must be initiated immediately and vaccines are administered less than 2 weeks before starting Ultomiris therapy. The recommended dosing regimen for adult patients (≥ 18 years of age) with PNH consists of a loading dose followed by maintenance dosing, administered by intravenous infusion. Administer the doses based on the patient’s body weight, as shown below. Starting 2 weeks after the loading dose administration, begin maintenance doses at a once every 8-week interval. The dosing schedule is allowed to occasionally vary within 7 days of the scheduled infusion day (except for the first maintenance dose of Ultomiris) but the subsequent dose should be administered according to the original schedule. For patients switching from eculizumab to Ultomiris, administer the loading dose of Ultomiris 2 weeks after the last eculizumab infusion, and then administer maintenance doses once every 8 weeks, starting 2 weeks after loading dose administration.
Body Weight Range (kg): greater than or equal to 40 to less than 60; Loading Dose (mg): 2,400; Maintenance Dose (mg): 3,000
Body Weight Range (kg): greater than or equal to 60 to less than 100; Loading Dose (mg): 2,700; Maintenance Dose (mg): 3,300
Body Weight Range (kg): greater than or equal to 100; Loading Dose (mg): 3,000; Maintenance Dose (mg): 3,600
Ultomiris is specifically indicated for the treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA) for adult and pediatric (one month of age and older) patients.
Ultomiris is supplied as an injection for intravenous infusion. The recommended dosing regimen in adult and pediatric patients one month of age and older with aHUS weighing 5 kg or greater, consists of a loading dose followed by maintenance dosing, administered by intravenous infusion. Administer the doses based on the patient’s body weight, as shown in the table in the drug's prescription label. Starting 2 weeks after the loading dose administration, begin maintenance doses once every 8 weeks or every 4 weeks (depending on body weight). The dosing schedule is allowed to occasionally vary within 7 days of the scheduled infusion day (except for the first maintenance dose of ULTOMIRIS); but the subsequent doses should be administered according to the original schedule.
PNH: The FDA approval of Ultomiris was based on two open-label, randomized, active controlled, non-inferiority Phase III studies: PNH Study 301 and PNH Study 302. Study 301 enrolled patients with PNH who were complement inhibitor naïve and had active hemolysis. Study 302 enrolled patients with PNH who were clinically stable after having been treated with eculizumab for at least the past 6 months. In both studies, Ultomiris was dosed intravenously in accordance with the weight-based dosing (4 infusions of Ultomiris over 26 weeks). Eculizumab was administered on Days 1, 8, 15, and 22, followed by maintenance treatment with 900 mg of eculizumab on Day 29 and every 2 weeks (q2w) thereafter for a total of 26 weeks of treatment, according to the approved dosing regimen of eculizumab which was the standard-of-care for PNH at the time of studies. In both trials results demonstrated that Ultomiris had similar results to eculizumab (non-inferiority achieved): patients did not receive a transfusion and had similar incidence of hemolysis measured by the normalization of lactate dehydrogenase (LDH) levels in patients’ blood (LDH is an enzyme required during the process of turning sugar into energy in the body’s cells).
aHUS: The FDA approval of Ultomiris for atypical hemolytic uremic syndrome (aHUS) was based on data from two global, single-arm open-label studies – one in adults and one in children, referred to as pediatrics in the study – with aHUS. The pediatric study is ongoing and a total of 14 out of 16 children were enrolled and included in the interim analysis. Efficacy evaluation of Complete TMA Response was defined by hematologic normalization parameters (platelet count and LDH) and improved kidney function (as measured by ≥ 25 percent improvement in serum creatinine from baseline). In the initial 26-week treatment periods, 54 percent of adults and 71 percent (interim data) of children demonstrated Complete TMA Response. Treatment with Ultomiris resulted in reduced thrombocytopenia (low blood platelet count) in 84 percent of adults and 93 percent of children, reduced hemolysis (the destruction of red blood cells) in 77 percent of adults and 86 percent of children, and improved kidney function in 59 percent of adults and 79 percent (interim data) of children (for patients on dialysis at enrollment, baseline was established after they had come off dialysis).
Adverse effects associated with the use of Ultomiris for PNH may include, but are not limited to, the following:
- upper respiratory infection
Adverse reactions associated with the use of Ultomiris for aHUS may include, but are not limited to, the following:
- upper respiratory tract infection
The Ultomiris drug label comes with the following Black Box Warning: Life-threatening meningococcal infections/sepsis have occurred in patients treated with Ultomiris and may become rapidly life-threatening or fatal if not recognized and treated early. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies. Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Ultomiris, unless the risks of delaying Ultomiris therapy outweigh the risks of developing a meningococcal infection. Vaccination reduces, but does not eliminate, the risk of meningococcal infection. Monitor patients for early signs of meningococcal infections, and evaluate immediately if infection is suspected. Ultomiris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Ultomiris REMS, prescribers must enroll in the program.
Mechanism of Action
Ultomiris (ravulizumab-cwvz) is a terminal complement inhibitor that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a (the proinflammatory anaphylatoxin) and C5b (the initiating subunit of the terminal complement complex [C5b-9]) and preventing the generation of the terminal complement complex C5b9. Ultomiris inhibits terminal complement-mediated intravascular hemolysis in patients with PNH.
For additional information regarding Ultomiris or paroxysmal nocturnal hemoglobinuria, please visit https://www.ultomiris.com/