Ultomiris (ravulizumab-cwvz)

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

Approval Status:

Approved October 2019

Specific Treatments:

atypical hemolytic uremic syndrome in adults and pediatrics

Therapeutic Areas

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General Information

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

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.

Clinical Results

FDA Approval

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).

Side Effects

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

upper respiratory tract infection

diarrhea

nausea

vomiting

headache

hypertension

pyrexia

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 humanized monoclonal antibody. 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 and complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS.

Additional Information

For additional information regarding Ultomiris or aHUS, please visit the Ultomiris web page.