Paroxysmal Nocturnal Hemoglobinuria (PNH)


Soliris® was developed by Alexion Pharmaceuticals and was the first drug to be approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) by the US Food and Drug Administration (FDA), in 2007.1,2 Soliris is also approved for treatment of PNH in the European Union and Japan.2

Indications

Soliris is indicated for the reduction of hemolysis in patients with PNH,3 a rare blood disease in which defective blood cells that develop from abnormal hematopoietic stem cells are targeted by the complement system.2 Hemolysis and thrombosis are characteristic of PNH.1 

Get full prescribing information for Soliris at MPR

Mechanism of Action 

The active ingredient of Soliris is the complement inhibitor eculizumab, which is a recombinant humanized monoclonal antibody.3 Eculizumab binds specifically and with high affinity to C5 complement protein,3 thereby preventing C5 from being cleaved into C5a and C5b and limiting production of the terminal complement complex C5b-9. In PNH, eculizumab inhibits terminal complement-mediated intravascular hemolysis.3

Read more about PNH pathophysiology

Administration

The recommended dose of Soliris in adults with PNH is 600 mg every week for 4 weeks, followed by 900 mg in week 5 and then 900 mg every 2 weeks after the fifth dose.3 Soliris is supplied in 30 mL single-dose vials and is a colorless, clear, and sterile 10-mg/mL solution for intravenous use.3

Adverse Effects

The most frequently reported adverse reactions following the administration of Soliris to patients with PNH include headache, nasopharyngitis, back pain, and nausea.3

Read more about PNH complications

Warnings and Precautions

Soliris is available to patients only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) because of the risk for life-threatening infections that have been associated with its administration.3 Soliris can increase patients’ susceptibility to serious meningococcal infections (septicemia and/or meningitis), and although the risk for infection is reduced by vaccination, it is not eliminated.3 Patients should receive the meningococcal vaccine at least 2 weeks before the first dose is administered.3

Soliris is contraindicated for patients presenting with unresolved serious Neisseria meningitidis infection and/or for patients without current vaccination against N. meningitidis unless it has been determined that the risk of delaying Soliris treatment outweighs the risk for the development of a meningococcal infection.3 

Read more about PNH prognosis

Safety and Efficacy in Trials

The safety and efficacy of Soliris have been evaluated in a 26-week phase 3 clinical trial (NCT00122330).4 In this randomized, double-blind, placebo-controlled study, which included 87 transfusion-dependent patients with PNH, 43 were randomized to receive Soliris and 44 were randomized to placebo.5 The safety of the drug was also evaluated over a period of 52 weeks in a multicenter, single-arm phase 3 trial that enrolled 97 patients who had received at least one transfusion in the 24 months preceding the trial (NCT00122304),6 and in a long-term phase 3 extension study (NCT00122317)7 of 187 patients who were followed for between 10 and 54 months.2

Patients in the 3 trials received meningococcal vaccine before treatment, after which Soliris was administered intravenously at doses of 600 mg every 7 ± 2 days for 4 weeks, 900 mg 7 ± 2 days later, then 900 mg every 14 ± 2 days for the remainder of the study.3 

In the first trial, a significant reduction in hemolysis was observed in the patients who received Soliris vs those who received placebo; treatment with Soliris led to a decrease in the severity of anemia, stabilization of the hemoglobin levels, and a decreased need for transfusions in comparison with placebo.5 Additionally, clinically significant improvements were observed in the treated patients’ quality of life.5 The second trial reported a reduction in intravascular hemolysis that was sustained during the treatment period and led to a reduced need for transfusions, as well as less fatigue. In the extension study, intravascular hemolysis was reduced during the administration of Soliris and fewer thrombotic events were reported, even though most of the patients were receiving anticoagulants.3,8 

Read more about PNH clinical trials

References

1. Paroxysmal nocturnal hemoglobinuria. NORD (National Organization for Rare Disorders). Accessed November 19, 2022.

2. SOLIRIS® (eculizumab). Alexion AstraZeneca Rare Disease. Accessed November 19, 2022.

3. Soliris® (eculizumab). Prescribing information. Alexion Pharmaceuticals; revised November 2020.

4. Study using eculizumab in transfusion dependent paroxysmal nocturnal hemoglobinuria (PNH) patients. ClinicalTrials.gov. July 22, 2005. Updated December 4, 2006. Accessed November 19, 2022.

5. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355(12):1233-1243. doi:10.1056/NEJMoa061648

6. Study of safety in hemolytic paroxysmal nocturnal hemoglobinuria (pnh) patients treated with eculizumab. ClinicalTrials.gov. July 22, 2005. Updated February 21, 2007. Accessed November 19, 2022.

7. Extension study of eculizumab in patients with transfusion dependent paroxysmal nocturnal hemoglobinuria (PNH). ClinicalTrials.gov. July 22, 2005. Updated March 13, 2018. Accessed November 19, 2022.

8. Hillmen P, Muus P, Dührsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007;110(12):4123-4128. doi:10.1182/blood-2007-06-095646

Reviewed by Kyle Habet, MD, on 11/29/2022.

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