Soliris was approved by the U.S. Food and Drug Administration (FDA) in 2011 for all aHUS patients. In the same year, the European Commission granted marketing authorization for Soliris to treat children and adults with aHUS.
How does Soliris work?
The complement pathway is a component of the body’s immune system that marks pathogens for targeting by immune cells. aHUS is a genetic disorder in which mutations in complement pathway genes such as CFH, MCP (CD46), and CFI cause the uncontrolled activation of the alternative complement pathway, leading to thrombotic microangiopathy (TMA) — clots in small blood vessels.
In the alternative complement pathway, the complement protein C5 is cleaved into two forms called C5a and C5b by the enzyme C5 convertase. While C5a is a pro-inflammatory molecule, C5b combines with other proteins to form the C5b-9 terminal membrane attack complex. C5b-9 is known to promote clotting within blood vessels via the aggregation, or bringing together, of platelets.
Soliris is a humanized monoclonal antibody that binds to C5 and prevents its cleavage into C5a and C5b. This prevents the formation of the terminal complement complex C5b-9 and stops clotting within blood vessels.
Soliris in clinical trials
Two open-label Phase 2 clinical trials, C08-002 and C08-003, assessed the safety and effectiveness of Soliris in aHUS patients. The trials involved a total of 37 patients — 17 in C08-002 and 20 in C08-003.
C08-002 (NCT00844545 and NCT00844844) tested Soliris in therapeutic plasma exchange-resistant adult and adolescent aHUS patients, respectively. These patients had thrombocytopenia (low platelet counts) and kidney damage.
C08-003 (NCT00838513 and NCT00844428) tested Soliris in therapeutic plasma exchange-sensitive adult and adolescent aHUS patients, respectively. These patients had kidney damage, but with no more than 25% decrease in their platelet count during prolonged plasma therapy (at least eight weeks).
The results showed Soliris could inhibit complement-mediated TMA and improve kidney function in aHUS patients.
C10-004, another open-label Phase 2 exploratory trial (NCT01194973), assessed the effectiveness of Soliris in adult aHUS patients. The results showed that sustained Soliris treatment reduced complement activation, inflammation, clot formation, blood vessel damage, and kidney injury.
An open-label Phase 2 trial (NCT01193348) assessed the safety and effectiveness of Soliris in 22 children with aHUS, ages 1 month to 18 years. The study showed that Soliris was well tolerated with no adverse side effects, and 64% of the treated patients showed complete response to treatment, which means the symptoms disappeared.
An open-label Phase 2 trial (NCT03518203) is underway to study the effects of early intervention with Soliris to treat TMA/aHUS-associated multi-organ dysfunction syndrome (MODS) in children and adults undergoing hematopoietic stem cell transplantation (HCT). The trial is currently recruiting about 21 patients in the U.S., and is expected to be completed in December 2023.
The recommended dose of Soliris is administered intravenously (injected into a vein) for about 35 minutes in adults and about one to four hours in children. Adults receive a weekly dose of Soliris once every five weeks and subsequently, once every two weeks.
Discontinuation or deviation from the recommended Soliris dosing schedule can put patients at risk of TMA-associated complications. If the treatment is discontinued, patients should be monitored for at least 12 weeks.
Patients on Soliris therapy are at an increased risk of acquiring life-threatening meningococcal infections and must be immunized at least two weeks before starting Soliris therapy.
Soliris is available only through the FDA’s risk evaluation and mitigation strategy, in which the clinician should evaluate if the potential benefits of Soliris therapy outweigh the risks of serious side effects.
Last updated: Feb. 3, 2020
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