Long-term Ultomiris continues to control aHUS in adults, children: New data
Patients of all ages see benefits with treatment up to 2 years in trials
Long-term treatment with Ultomiris (ravulizumab) led to sustained clinical improvements for adults and children with atypical hemolytic uremic syndrome (aHUS), according to new two-year data from a pair of clinical trials.
Patients in both age groups saw improvements in blood-related health factors and kidney function, and experienced less fatigue than they had before treatment started.
“These results from a 2-year analysis of Phase 3 trial data demonstrated that the improved clinical outcomes and quality of life benefits achieved in adult and pediatric patients with aHUS treated with [Ultomiris] are maintained long-term,” the researchers wrote, noting that treatment was given “over 2 years with maintenance dosing every 4-8 weeks.”
Overall, “we found that treating patients for 2 years with [Ultomiris] was associated with improved blood health, kidney function, and quality of life and was well tolerated,” the team wrote.
The study, “Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials,” was published in the journal Kidney Medicine. The work was funded by Alexion, Astrazeneca Rare Disease, which markets Ultomiris and Soliris (eculizumab), another approved aHUS therapy.
Safety, efficacy of Ultomiris investigated in 2 Phase 3 trials
In aHUS, abnormal activation of the immune system’s complement cascade causes blood clots to form in the body’s small blood vessels, driving damage to the kidneys and other organs.
aHUS is a type of thrombotic microangiopathy, or TMA, disorders in which small blood vessel damage is associated with three core symptoms: red blood cell destruction, known as hemolysis, low blood platelet counts, and kidney damage.
Both Ultomiris and Soliris work to block complement activation by targeting a protein called C5, thereby easing the symptoms of aHUS. Ultomiris is designed to last longer in the bloodstream and requires less frequent dosing than the older medication.
To know more about the safety and efficacy of Ultomiris, a pair of open-label Phase 3 clinical trials evaluated the therapy in either adults or children with aHUS. One trial (NCT02949128) enrolled 58 adults who had never been on a C5 inhibitor. The other trial (NCT03131219) recruited 34 children, 24 of whom were C5 inhibitor-naïve and 10 who switched from Soliris.
In both trials, participants received infusions of Ultomiris into the bloodstream every one or two months at a weight-based dose after an initial loading dose. After the first six months of treatment, patients could continue on for up to 4.5 years or until the therapy’s regulatory approval.
Among C5 inhibitor-naïve patients, the main goal was to evaluate the proportion of those who achieved a complete TMA response after six months. That was defined as achieving normalized platelet counts, and blood levels of lactate dehydrogenase, or LDH, a hemolysis marker, as well as a minimum 25% improvement in blood creatinine concentrations, a kidney damage marker, relative to the study’s start, or baseline. This response had to be seen at two consecutive assessments taken at least a month apart.
The results showed that this goal was met by more than 50% of adults and by more than 70% of C5 inhibitor-naïve children after six months. Children who had switched from Soliris continued to have stable blood and kidney measurements after starting Ultomiris.
New analysis looks at trial data after 2 years
Now, the scientists are reporting two-year follow-up findings from both studies, which generally indicated that the benefits of treatment had been sustained and that the proportion of treatment responders slightly increased over time.
Specifically, 61% of adults and 90% of inhibitor-naïve children had achieved a complete TMA response at the two-year mark.
In the adult group, 86% achieved platelet normalization, 88% achieved LDH normalization, and 63% saw at least a 25% improvement in creatinine. For children, LDH and platelet normalization occurred in 95%, while creatinine improvements occurred in 90%.
Improvements in kidney function that had been observed after six months were also generally maintained at the two-year follow-up mark. More than half of adults who required dialysis to support kidney function at baseline were able to discontinue it. All inhibitor-naïve children who required dialysis at the study’s start were able to stop such treatment over the course of two years.
For children who switched from Soliris, improvements in kidney function seen with that medication were generally maintained after starting Ultomiris.
Reductions in fatigue were observed as soon as six months after starting treatment and were also maintained over the two-year period.
C5 levels, which had been rapidly reduced once Ultomiris was started, also remained low over time in all groups.
These 2-year data support the favorable benefit/risk profile of [Ultomiris] and its long-term use in all patients with aHUS.
The treatment was generally well tolerated, with a safety profile similar to previous reports and with most side effects occurring during the first six months of treatment.
Overall, “long-term treatment with [Ultomiris] was well tolerated and associated with continual improvement in TMA response and kidney function in adults and pediatric patients with aHUS,” the team wrote.
“These 2-year data support the favorable benefit/risk profile of [Ultomiris] and its long-term use in all patients with aHUS,” the researchers wrote.
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