Soliris in aHUS Patients with Progressing TMA Despite Intensive PE/PI
In an oral presentation today, researchers presented two-year follow-up data from a prospective, open-label, single-arm phase 2 study in 17 adult and adolescent patients with aHUS who had presented with progressive clinical TMA complications despite intensive plasma exchange or plasma infusion (PE/PI). Patients had been diagnosed with aHUS for a median of 10 months before the start of the study, and 71% had severe renal impairment, with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m
at baseline. Seventeen patients were enrolled in the initial study and received Soliris for 26 weeks. Thirteen of the 17 patients continued into a long-term extension phase. Patients were evaluated for a median duration of 100 weeks. Data for all 17 patients were analyzed using repeated measures models and response through data cutoff for each patient.
The study achieved its primary endpoint, as mean platelet count improved from baseline at 26 weeks (p=0.0001). Additionally, the improved platelet count continued over two years (p<0.001), indicating sustained inhibition of complement-mediated TMA with ongoing eculizumab treatment. Platelet normalization (≥150x10
/L) was achieved in 13 of 15 patients (87%) who had low platelets at baseline by 26 weeks and was maintained through two years for 12 of the 13 patients. TMA event-free status (at least 12 consecutive weeks of stable platelet count, no PE/PI, and no new dialysis) was also achieved rapidly and maintained through two years. Specifically, 15 of 17 (88%) Soliris-treated patients achieved TMA event-free status through each data cut-off point (26 weeks, one year, and two years), and TMA event-free status was achieved regardless of the identification of a genetic complement mutation. Hematologic normalization also improved with chronic Soliris treatment over two years: 13 of 17 (76%) Soliris-treated patients achieved and maintained hematologic normalization through 26 weeks, and 15 of 17 (88%) Soliris-treated patients achieved and maintained hematologic normalization through one year and two years.
Investigators also observed that chronic Soliris treatment was associated with a sustained improvement in eGFR with a mean change from baseline of 32.0 mL/min/1.73m
through 26 weeks (p=0.001) and 35.2 mL/min/1.73m
through two years (p=0.0005). Improvement in eGFR was rapid over the first 4 weeks (positive rate of change p<0.0001), and continued to improve with further Soliris treatment from week 4 through two years (p=0.03). Chronic kidney disease (CKD) improvement of at least one stage was reported in 10 patients (59%) at 26 weeks and in 12 patients (71%) at two years. A serum creatinine improvement of at least 25% was observed in 11 patients (65%) at 26 weeks and in 13 patients (76%) at two years. Soliris treatment also eliminated the need for dialysis in four of five patients receiving dialysis at baseline. The researchers also observed that earlier intervention with Soliris was associated with greater increases in eGFR (p<0.01). In addition, Soliris significantly improved quality of life over two years (p<0.0001).
“The two-year data show that longer Soliris treatment led to continued improvements and better outcomes for patients with aHUS, including sustained inhibition of complement-mediated TMA, a reduced burden of TMA interventions, and markedly improved renal function,” said Christophe Legendre, M.D., Professor of Nephrology at the University of Paris Descartes and Hôpital Necker in Paris, France, who presented the data at ASN. “Moreover, earlier treatment was associated with better renal outcomes. No deaths were reported during the two-year study, providing further evidence of the long-term benefits of Soliris in this devastating and life-threatening disease.”