Crovalimab for paroxysmal nocturnal hemoglobinuria
Last updated March 20, 2024, by Marisa Wexler, MS
Fact-checked by Patrícia Silva, PhD
What is crovalimab for PNH?
Crovalimab is a subcutaneous (under-the-skin) injection therapy that Roche’s subsidiary Genentech is developing to treat paroxysmal nocturnal hemoglobinuria (PNH). The therapy seeks to reduce the destruction of red blood cells in people with PNH.
Crovalimab was approved to treat PNH in China in February 2024. It is being reviewed by the U.S. Food and Drug Administration, with a decision expected in the summer 2024. Applications also are being reviewed in Japan and the European Union.
Therapy snapshot
Treatment name: | Crovalimab |
Administration: | Subcutaneous injection |
Clinical testing: | Has completed Phase 3 testing, applications seeking approval in the U.S. and elsewhere currently under review |
How does crovalimab work in PNH?
In PNH, blood cells are produced that lack certain proteins on their surface. As a result, a part of the immune system called the complement system becomes abnormally activated and destroys blood cells, driving disease symptoms.
Crovalimab is designed to stop blood cell destruction — a process called hemolysis — by blocking the activation of the complement system. The therapy specifically inhibits a complement protein called C5.
Two approved PNH therapies — Soliris (eculizumab) and Ultomiris (ravulizumab), both marketed by AstraZeneca — also target C5. Genentech is developing crovalimab to provide a more convenient dosing regimen than either Soliris, which is given by infusion into the bloodstream every other week, or Ultomiris, which is given by infusion every other month or by subcutaneous injection once weekly.
How will crovalimab be administered in PNH?
In clinical trials, a first loading dose of crovalimab was given by injection into the bloodstream, or intravenous infusion, at a dose of 1,000 mg for patients weighing between 40 and 100 kg (about 88 to 220 pounds) or 1,500 mg for patients 100 kg or heavier.
Starting the day after the loading dose, the next four doses were given by subcutaneous injection at a dose of 340 mg once weekly. Thereafter, injections were administered every four weeks at 680 mg for patients weighing 40 to 100 kg, or 1,020 mg for patients 100 kg or heavier.
Crovalimab subcutaneous injections can be done at home by patients or caregivers.
Crovalimab in PNH clinical trials
The Phase 1/2 COMPOSER trial (NCT03157635) tested the safety and pharmacological properties of crovalimab in healthy volunteers. Results showed no serious side effects.
The second part of the study tested crovalimab in 29 people with PNH, 19 who’d previously been on other complement-blocking therapies and 10 who hadn’t been treated before. Treatment with crovalimab reduced C5 activation and hemolysis, the findings suggested.
Long-term findings from COMPOSER’s open-label extension suggested these effects were generally maintained with long-term treatment, and most patients did not need blood transfusions with long-term crovalimab. Over a median of three years of follow-up, five patients each had one instance of breakthrough hemolysis, or new hemolysis that had previously been controlled, which in all cases resolved with continuous treatment.
Phase 3 COMMODORE 2 trial
The Phase 3 COMMODORE 2 trial (NCT04434092) enrolled 204 people with PNH who hadn’t before received disease-specific treatment. The study was open to patients of any age who weighed at least 40 kg (about 88 pounds). The participants were randomly assigned to treatment with crovalimab or with Soliris for about six months.
The study’s main goal was to test whether crovalimab was non-inferior to Soliris at preventing the need for blood transfusions. Results showed about two-thirds of patients on either therapy didn’t require transfusions during the trial (65.7% with crovalimab, 68.1% with Soliris). In both treatment groups, just under 80% of patients had no hemolysis during the trial. Both therapies led to clinically significant decreases in patient-reported measures of fatigue, and rates of side effects also were comparable, with no serious safety issues related to either therapy reported.
Phase 3 COMMODORE 3 trial in China
The Phase 3 trial COMMODORE 3 (NCT04654468) enrolled 51 people with PNH, ages 12 and older, at several centers in China. Results showed that, over about six months on crovalimab, 78.7% of patients had hemolysis control, with just one instance of breakthrough hemolysis. More than half were free from blood transfusions, and patient-reported fatigue eased meaningfully for most participants. The therapy was generally well tolerated; there was one serious infection deemed a treatment-related side effect.
Ongoing trials
An ongoing Phase 3 trial called COMMODORE 1 (NCT04432584) is testing crovalimab against Soliris in people with PNH who have previously been on a stable regimen of Soliris. As of March 2024, the trial was still recruiting participants at more than 100 sites worldwide. The study is open to patients of any age who weigh at least 40 kg.
An interim analysis from COMMODORE 1, announced in 2023, indicated similar efficacy for both crovalimab and Soliris. About three-quarters of patients on either therapy were free from blood transfusions over the available follow-up.
Common side effects of crovalimab
Side effects related to crovalimab reported in clinical trials include:
- headache
- rash
- upper respiratory infection
- weight gain.
Since crovalimab is designed to block part of the immune system, it may increase the risk of infections.
PNH News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
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