Ultomiris (ravulizumab)

In PNH, red blood cells are missing protective proteins on their surface, and the complement system attacks them. The final step depends on a protein called C5 being split into C5a and C5b, which builds a pore called the membrane attack complex that bursts red cells inside blood vessels (intravascular hemolysis)^[2].

Ravulizumab is a lab-made antibody that binds C5 and stops it from being split, so the pore cannot form^[2]. It works on the same target as eculizumab (Soliris), but it lasts longer in the body, which is why maintenance doses are spaced 8 weeks apart for most people instead of 2. Like other C5 inhibitors, it does not stop red cells from being cleared in the spleen and liver (extravascular hemolysis). Danicopan (Voydeya) is an approved add-on pill for that problem in people who stay on Ultomiris^[4].

Ultomiris carries a boxed warning for serious meningococcal infections. It raises the risk of life-threatening or fatal infections caused by Neisseria meningitidis, even in people who have been vaccinated. Meningococcal vaccines for serogroups A, C, W, Y and B must be completed or updated at least 2 weeks before the first dose, unless waiting would be riskier. Ultomiris is available only through a restricted program called the ULTOMIRIS and SOLIRIS REMS, and patients carry a Patient Safety Card during treatment and for 8 months after the last dose^[2].

In the 2 adult PNH trials, which compared Ultomiris with eculizumab, the most common side effects on Ultomiris were upper respiratory tract infection (39% vs 39% on eculizumab) and headache (32% vs 26%). Diarrhea (9% vs 5%), nausea (9% vs 9%) and fever (7% vs 8%) were also reported. Serious side effects occurred in 6.8% of adults on Ultomiris, and 1 person died of sepsis. Infusion reactions occurred in about 1% of people with PNH^[2].

The label also warns about other serious infections, including from Streptococcus pneumoniae, Haemophilus influenzae and gonorrhea, and children should get pneumococcal and Hib vaccines. Stopping Ultomiris can bring hemolysis back, so the label calls for monitoring for at least 16 weeks after stopping. Breastfeeding should stop during treatment and for 8 months after the last dose^[2].

Ultomiris is given by IV infusion through a filter by a healthcare provider. The dose depends on body weight. Treatment starts with a loading dose, and the first maintenance dose comes 2 weeks later^[2].

Doses for PNH by body weight, loading then maintenance:

- 5 kg to under 10 kg: 600mg, then 300mg every 4 weeks

- 10 kg to under 20 kg: 600mg, then 600mg every 4 weeks

- 20 kg to under 30 kg: 900mg, then 2,100mg every 8 weeks

- 30 kg to under 40 kg: 1,200mg, then 2,700mg every 8 weeks

- 40 kg to under 60 kg: 2,400mg, then 3,000mg every 8 weeks

- 60 kg to under 100 kg: 2,700mg, then 3,300mg every 8 weeks

- 100 kg or more: 3,000mg, then 3,600mg every 8 weeks

The label sets minimum infusion times by weight. For adults 40 kg and over they range from 0.4 to 0.9 hours, and for the smallest children the loading dose takes at least 1.4 hours. Patients are watched for at least 1 hour after each infusion. A dose can occasionally move up to 7 days from the scheduled day, except the first maintenance dose. People switching from eculizumab get the Ultomiris loading dose when their next eculizumab dose would have been due^[2].

Every 8 weeks for people who weigh 20 kg or more, after a loading dose.

Starting: A weight-based loading dose, then the first maintenance dose 2 weeks later.

Smaller children: Every 4 weeks for children from 5 kg to under 20 kg.

Flexibility: A dose can occasionally move up to 7 days from the scheduled day, except the first maintenance dose.

Source: FDA label for Ultomiris, DailyMed, effective October 2025

Both block complement protein C5 and come from Alexion, but Ultomiris lasts longer, so doses are further apart.

Schedule: Ultomiris is every 8 weeks for most people. Soliris is every 2 weeks after 5 weekly starting doses.

Age: Ultomiris is approved for PNH from 1 month of age. The Soliris label gives PNH dosing for adults only.

Trial results: In 2 trials of 441 adults, Ultomiris was not worse than Soliris at controlling red cell destruction. The trials were not designed to show it was better.

Safety: Both carry the same meningococcal boxed warning and share 1 REMS program. The safety card period is 8 months after Ultomiris and 3 months after Soliris.

Source: FDA label for Ultomiris, DailyMed; FDA label for Soliris, DailyMed

Yes, the label gives a switching plan.

Timing: The Ultomiris loading dose is given when your next Soliris dose would have been due, and maintenance starts 2 weeks later.

Evidence: In Study 302, 195 adults stable on Soliris were randomly assigned to switch or stay. LDH and transfusion results were similar, and no one who switched had breakthrough hemolysis over 26 weeks, against 5.1% who stayed on Soliris.

Source: FDA label for Ultomiris, DailyMed, effective October 2025

Yes, for children 1 month and older who weigh at least 5 kg.

Approval: The FDA added children to the PNH approval on June 7, 2021.

Evidence: A trial of 13 children aged 9 to 17 found results similar to adults. Use in children under 9 and under 30 kg is based on drug-level and safety data from PNH and aHUS studies.

Vaccines: Children also need pneumococcal and Hib vaccines per ACIP.

Source: FDA label for Ultomiris, DailyMed; Drugs@FDA

Usually under 1 hour for adults, plus at least 1 hour of observation.

Adults: The label's minimum infusion times for people 40 kg and over range from 0.4 to 0.9 hours, depending on weight and whether it is a loading or maintenance dose.

Children: Small children need longer, up to at least 1.4 hours for a loading dose at 5 kg to under 10 kg.

Source: FDA label for Ultomiris, DailyMed, effective October 2025

The most common were upper respiratory tract infection and headache.

Adult trials: Upper respiratory infection 39% on Ultomiris and 39% on eculizumab; headache 32% vs 26%; diarrhea 9% vs 5%.

Serious: Serious side effects occurred in 6.8% of adults on Ultomiris, and 1 person died of sepsis.

Boxed warning: Serious meningococcal infections, which can be fatal even after vaccination.

After stopping: Monitoring for at least 16 weeks for returning hemolysis.

Source: FDA label for Ultomiris, DailyMed, effective October 2025

Yes, for people with commercial insurance.

Copay program: Alexion says eligible commercially insured patients enrolled in OneSource may pay as little as $0.

Not eligible: Medicare, Medicaid and other federal or state plans. OneSource says it can point those patients to third-party resources.

Contact: Alexion OneSource at 1-888-765-4747.

Source: Alexion OneSource, Ultomiris financial assistance