Platelet counts may predict long-term Ultomiris response in aHUS: Study
Platelet response in first 2 weeks tied to kidney recovery at 6 months
Changes in platelet counts over the first two weeks on Ultomiris (ravulizumab-cwvz) in people with atypical hemolytic uremic syndrome (aHUS) may help predict the patients’ long-term response to such treatment, according to a new study.
An analysis found that patients’ early platelet responses were linked to kidney improvements at the six-month mark of a Phase 3 clinical trial. While the researchers noted that most patients are on treatment for longer than 26 weeks, or six months, the team suggested that tracking platelet counts in the first weeks on Ultomiris may be a predictor of long-term response.
“This study demonstrated that the platelet response to [Ultomiris] in the early treatment period was associated with [the] achievement of renal [kidney] recovery within 26 weeks in patients with aHUS,” the researchers wrote.
The study, “Correlation between a 2-week change in platelet count and clinical outcomes after the initiation of ravulizumab treatment in adult patients with atypical hemolytic uremic syndrome: post-hoc analysis of the phase III trial,” was published in the Thrombosis Journal. The work was funded by Alexion AstraZeneca Rare Disease, the company that markets Ultomiris. The research team comprised one scientist from the company, three from Alexion Pharma, and two from two different universities in Japan.
Normal platelet counts seen for 85% of Ultomiris patients with renal recovery
aHUS is caused by the overactivity of part of the immune system called the complement cascade. Abnormal complement activation leads to the formation of blood clots inside small blood vessels, which causes damage to the body’s organs, especially the kidneys. This, along with hemolytic anemia — anemia driven by red blood cell destruction — and low platelet counts are the key hallmarks of thrombotic microangiopathy, or TMA, a group of conditions that also includes aHUS.
Ultomiris is an approved aHUS treatment that works to block complement activation. It has been shown to resolve complement-mediated TMA, and to improve kidney function in people with the disease.
However, not everyone with aHUS will respond to Ultomiris, and it can take some time to detect whether or not the therapy is having an impact on TMA or kidney health.
“It has been proposed to regularly monitor platelet counts as an early response to [Ultomiris],” the researchers wrote. They noted, however, that neither the timing nor exact platelet count levels associated with treatment response have been established.
Seeking to identify early markers of treatment response, the team of scientists now conducted an analysis of data from a Phase 3 clinical trial (NCT02949128), completed in early 2023, that helped prove the efficacy of Ultomiris in treating aHUS.
The analysis covered data from 56 adults with aHUS, all of whom were treated with Ultomiris. After six months on the therapy, 30 patients had achieved a complete TMA response — meaning they met prespecified thresholds for reductions in markers of kidney damage and red blood cell destruction, as well as normalization in platelet counts.
The results showed that 28 (93.3%) of the patients achieving a complete TMA response had experienced a normalization in platelet counts within the first two weeks of being on Ultomiris. In contrast, fewer than 27% of patients who didn’t have a complete TMA response had platelet normalization in the first two weeks of treatment.
Similar results were seen when looking at the endpoint of renal recovery, defined as an improvement in kidney function markers and/or discontinuation of dialysis. Dialysis is a type of treatment used to remove waste and excess fluids from the blood when the kidneys are no longer able to perform their normal function.
Platelet count normalization within the first 15 days of treatment was observed in 85.7% of patients achieving renal recovery and in 23.8% of those who failed to attain that milestone.
Although renal recovery in aHUS can often take much longer than the 26-week [six months] period analyzed in this study, our findings suggest that normalization of the platelet count … was associated with [the] achievement of renal recovery within the 26-week initial treatment period.
Statistical tests also showed that assessing if platelet counts normalized in the first two weeks of treatment could accurately predict whether or not patients would experience renal recovery in more than 80% of the cases, according to the researchers.
“Although renal recovery in aHUS can often take much longer than the 26-week period analyzed in this study, our findings suggest that normalization of the platelet count … was associated with [the] achievement of renal recovery within the 26-week initial treatment period,” the scientists wrote.
Based on these findings, the team argued that “monitoring of platelet counts during the early treatment period might be helpful to estimate the long-term response in complement inhibitor-naïve adults with aHUS.”
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