Soliris effective for PNH, even with bone marrow failure, study finds
Most Chinese patients in small study didn't need transfusions after 6 months
Most Chinese adults and adolescents with paroxysmal nocturnal hemoglobinuria (PNH) no longer require blood transfusions after a median of six months of treatment with Soliris (eculizumab).
That’s according to a small study at a single center in China, which also found the approved therapy to be safe and well tolerated.
Further, the researchers determined that Soliris effectively reduced the breakdown of red blood cells — a process known as hemolysis — both in patients with and without bone marrow failure. Such failure is a main cause of life-threatening complications and death in PNH.
“[Soliris] can effectively control the hemolytic symptoms of PNH with good tolerance for Chinese patients,” the researchers concluded.
Their study, “Eculizumab treatment for Chinese patients with hemolytic paroxysmal nocturnal hemoglobinuria (PNH): efficacy and safety – a single-center study,” was published in the journal Hematology.
Soliris was launched for PNH patients in China in 2022
In PNH, red blood cells break down as they are attacked by an overactive complement system — a group of proteins that normally work as part of the immune system to fight off infection. Hemolysis can occur inside or outside blood vessels, leading to many symptoms.
Soliris, the first treatment to receive widespread approval for PNH, works by blocking the activation of a complement protein called C5. By doing so, it prevents the complement system from attacking and destroying red blood cells inside blood vessels, easing symptoms.
“A substantial number of clinical trials and real-world studies have confirmed the efficacy and safety of [Soliris]. However, real-world data on the use of [Soliris] for PNH in China are relatively scarce, as the drug was launched in China by the end of 2022,” the researchers wrote.
To gain more insight into the effects of Soliris on Chinese people with PNH, the team reviewed the medical records of 48 patients, ages 12 to 78. All had started treatment with Soliris a median of 7.5 months after being diagnosed with PNH. Half of the patients had classic PNH, while the other 50% had PNH with bone marrow failure, which occurs when the bone marrow doesn’t produce enough blood cells.
Building on an earlier study with a smaller number of patients, “we expanded the sample size and extended the follow-up period by collecting data from a greater number of patients with longer follow-up periods,” the researchers wrote.
Overall, the patients were on Soliris for a median of six months, with treatment ranging from 3-15 months. Before Soliris, nearly half (48%) had received corticosteroids, and 40% — 19 patients — had been taking cyclosporine. One-third of the patients, or 16 in total, had received recombinant human erythropoietin, and nine (19%) had been given stanozolol.
More than one-third (37.5%) needed regular blood transfusions to make up for the lack of red blood cells. The most common symptom was fatigue, experienced by 92% of patients, followed by hemoglobinuria, which occurs when hemoglobin, the protein that carries oxygen in red blood cells, is present in the urine. Almost 80% of patients had experienced hemoglobinuria.
Patients with, without bone marrow failure saw reductions in fatigue
Over the course of treatment, Soliris significantly reduced the levels of lactate dehydrogenase, or LDH, an enzyme that’s released into the bloodstream when red blood cells are destroyed. More than half of the patients (58.3%) achieved normal levels within a median of one month, indicating that hemolysis was well under control.
Of the 18 patients who previously needed blood transfusions, 15 (83.3%) no longer required them after a median of one month on Soliris. At six months, one patient again needed a blood transfusion due to extravascular hemolysis, which is when hemolysis occurs outside blood vessels.
Before treatment, seven patients (14.6%) had chronic kidney disease. However, after up to three months on Soliris, the median levels of creatinine, a marker of kidney dysfunction, dropped significantly, indicating an improvement in kidney function, the researchers noted.
The findings … [demonstrate] the significant effectiveness of [Soliris], including sustained inhibition of intravascular hemolysis, improvement of anemia, and reduction of transfusion requirements.
Patients with or without bone marrow failure were similar in age and across a range of other characteristics. The exception was the levels of platelets, which were significantly lower in those with bone marrow failure. Platelets are small cell fragments that are produced in the bone marrow to help form blood clots to slow or stop bleeding.
The two groups responded similarly to Soliris, with both showing reductions in fatigue. This is important because “fatigue is commonly reported in patients with PNH and can impair their quality of life,” the researchers wrote.
Side effects were generally mild. Breakthrough hemolysis, which occurs when PNH symptoms suddenly come back despite treatment, occurred in eight patients (17.4%) and extravascular hemolysis in five (10.4%), indicating that some hemolysis persisted.
The team also looked at other research evaluating the use of Soliris for PNH patients, including “a Japanese study [that] found similar results.”
“The findings … are consistent with ours, demonstrating the significant effectiveness of [Soliris], including sustained inhibition of intravascular hemolysis, improvement of anemia, and reduction of transfusion requirements,” the researchers wrote. They noted, however, that “the follow-up period was not long enough to observe the long-term efficacy, side effects, and survival of patients.”
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