Soliris (eculizumab) maintenance treatment given every three weeks — instead of the standard two weeks — was sufficient to achieve therapeutic blood levels and prevent disease relapse for at least four years in a 2-year-old girl with atypical hemolytic uremic syndrome (aHUS), a case study shows.
Soliris’ optimized regimen was based on its pharmacokinetics (uptake, distribution, and elimination in the body) and pharmacodynamics (effects on the body) in the girl, and the researchers suggested their method be used in aHUS patients to reduce their treatment burden and costs.
The case report, “Pharmacokinetics and Pharmacodynamics Estimation of Eculizumab in a 2-Year-Old Girl With Atypical Hemolytic Uremic Syndrome: A Case Report With 4-Year Follow-Up,” was published in the journal Frontiers in Pediatrics.
Soliris, developed and marketed by Alexion, is an approved first-line treatment for aHUS. It works by specifically targeting a component (the C5 protein) of the complement system — a part of the immune system chronically and uncontrollably activated in aHUS patients.
By blocking the activity of the C5 protein, Soliris prevents small blood vessel destruction, formation of blood clots, and consequent organ damage — all hallmark features of this rare disease.
The therapy is administered intravenously (directly into the bloodstream) and involves a first induction phase followed by a maintenance phase of biweekly doses.
Soliris’ recommended maintenance regimen for aHUS children weighing less than 10 kilograms (about 22 pounds) is 300 mg every three weeks, which is shortened to 300 mg every two weeks when children weigh between 10 and 20 kg (about 44 pounds).
While Soliris has significantly improved the lives of aHUS patients, its high cost (more than $6,500 for a 300 mg vial) and need for biweekly intravenous administration — potentially for a lifetime — are a huge financial burden for patients and caregivers.
“Therefore, a personalized dosing regimen seems to be a viable solution for reducing the burden,” the researchers wrote.
Researchers in Japan, along with colleagues in the U.S., reported the case of a 2-year-old girl with aHUS whose disease was successfully controlled with a personalized, effective, Soliris maintenance treatment for at least four years.
The girl developed aHUS when she was 5 months old and due to a mutation in the C3 gene, which contains instructions to produce the C3 complement protein. She was successfully treated with Soliris’ recommended regimen following three days of hemodialysis and three plasma exchanges.
When she was 2 years old and weighing 14 kg (nearly 31 pounds), the researchers analyzed her Soliris blood levels as well as Soliris’ pharmacokinetics and pharmacodynamics to optimize her treatment regimen.
Pharmacokinetics analysis showed that Soliris was cleared by the girl’s body at a rate 40% lower than the reported aHUS population value. A pharmacokinetic simulation of Soliris blood levels when given at every two-, three-, and four-week intervals showed that the two- and three-week regimens were sufficient to achieve efficient Soliris trough levels (at least 100 μg/mL).
Notably, trough levels are the lowest therapy levels before the next dose is administered.
Based on those results, researchers decided to continue Soliris treatment at 300 mg every three weeks, instead of the two-week interval period recommended for her weight.
Two years of follow-up showed the girl (now weighing 17.5 kg, or about 38.5 pounds) had no disease recurrence, her blood tests were normal, and she had low or undetectable total complement activity (called CH50), suggesting that the personalized Soliris regimen was effective.
By that time, another pharmacokinetic simulation was conducted, which still suggested that the three-week interval regimen would remain effective, and treatment regimen was unchanged. At the latest follow-up date, the 6-year-old girl continued to show no signs of disease relapse, and her CH50 levels were maintained constantly at undetectably low levels. Soliris treatment at every three weeks is ongoing.
“This method allows for personalized treatment of patients, and reduces the patients’ burden and high medical costs,” the researchers wrote, adding that with the three-week regimen “the patient could skip 35 hospital visits and save $200,000 in medical costs”.
The team hopes that this case report “will facilitate [pharmacokinetics/pharmacodynamics]-based [Soliris] precision dosing in a larger number of patients to minimize their physical and economical burdens.”
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