National Stroke Foundation

Ultomiris (ravulizumab-cwvz)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

Approved December 2018

Specific Treatments:

paroxysmal nocturnal hemoglobinuria

Therapeutic Areas

General Information

Ultomiris (ravulizumab-cwvz) is a humanized monoclonal antibody. PNH is a rare acquired disorder that leads to the rupture or destruction of red blood cells (hemolysis). Ultomiris is a long-acting complement inhibitor that prevents hemolysis.

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

Clinical Results

FDA Approval

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).

Side Effects

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

upper respiratory infection

headache

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. 

Additional Information

For additional information regarding Ultomiris or paroxysmal nocturnal hemoglobinuria, please visit https://www.ultomiris.com/