Ultomiris (ravulizumab-cwvz) - 3 indications

Scroll down for more information on each indication:

• for the treatment of patients >1 month of age with paroxysmal nocturnal hemoglobinuria; approved December 2018
• for the treatment of patients >1 month of age with atypical hemolytic uremic syndrome; approved October 2019
• for the treatment of AChR-Positive Generalized Myasthenia Gravis; approved April of 2022

General Information

Ultomiris (ravulizumab-cwvz) is a humanized monoclonal antibody. 

Ultomiris is indicated for the the following:

• for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria.
• the treatment of adults and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA)
• for the treatment of AChR-Positive Generalized Myasthenia Gravis

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 in adult and pediatric patients, one month of age or older weighing 5 kg or greater, with PNH and aHUS consists of a loading dose followed by maintenance dosing, administered by intravenous infusion. The dosing is based on the patient’s body weight, as shown in the table below. Starting 2 weeks after the loading dose administration, begin maintenance doses once every 4 or 8 weeks (q4w or q8w), based 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); but the subsequent doses should be administered according to the original schedule.

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. 

Side Effects

Adverse effects associated with the use of Ultomiris for PNH may include, but are not limited to, the following:

• upper respiratory infection
• headache

Adverse reactions associated with the use of Ultomiris for aHUS may include, but are not limited to, the following:

• upper respiratory tract infection
• diarrhea
• nausea
• vomiting
• headache
• hypertension
• pyrexia

Adverse reactions associated with the use of Ultomiris for gMG may include, but are not limited to, the following:

• diarrhea
• 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.

Indication 1 - for the treatment of patients >1 month of age with paroxysmal nocturnal hemoglobinuria

approved December 2018

Clinical Trial Results

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).

Indication 2- for the treatment of patients >1 month of age with atypical hemolytic uremic syndrome

approved October 2019

Clinical Trial Results

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).

Indication 3 - AChR-Positive Generalized Myasthenia Gravis

approved April 2022

Clinical Trial Results

FDA approval was based on results from the global, randomized, double-blind, placebo-controlled, multicenter 26-week CHAMPION-MG trial.  Ultomiris was superior to placebo in the primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 26, a patient-reported scale that assesses patients’ abilities to perform daily activities.