Ultomiris Found to Be Safe, Effective for Pregnancy-related aHUS

Ultomiris (ravulizumab) can safely and effectively treat women with atypical hemolytic uremic syndrome (aHUS) whose symptoms are triggered by pregnancy, a Phase 3 clinical trial analysis reveals. 

The study, “Efficacy and safety of the long-acting C5 inhibitor ravulizumab in patients with atypical hemolytic uremic syndrome triggered by pregnancy: a subgroup analysis,” was published in the journal BMC Nephrology.

aHUS is caused by the abnormal activation of the complement system, a part of the immune system, resulting in the progressive destruction of red blood cells. It frequently leads to kidney problems, most notably thrombotic microangiopathy (TMA) — when the small blood vessels inside the kidneys become clogged, which can result in kidney failure.

While aHUS is a genetic disease, most patients only experience symptoms after a triggering event, such as pregnancy, which is reported as a trigger in 4% of cases. Pregnancy-related aHUS is a medical emergency requiring hospitalization and prompt treatment.

Ultomiris, developed by Alexion Pharmaceuticals, works by blocking the activity of the C5 complement protein, thereby blocking the over-activation of the complement system.

It is approved to treat adults and children with aHUS in the U.S., European Union, and Japan. Its use is supported by the Phase 3 clinical trials aHUS-311 (NCT02949128) and aHUS-312 (NCT03131219), which demonstrated efficacy and safety in children and adults with aHUS.

In the new analysis, investigators based at the University Duisburg-Essen in Germany, with colleagues at sites in Italy, Spain, Russia, and South Korea, and scientists at Alexion, examined outcomes in a group of eight participants from the aHUS-311 trial who developed aHUS postpartum and received Ultomiris.

The eight women ranged from 22 to 45 years old, with a median average age of 37.7 years. They also had never been treated with a C5 inhibitor.

Before treatment (baseline), all of the women experienced an acute, severe medical emergency associated with pregnancy or delivery, all had complicated deliveries, and most had complications before delivery. Five patients underwent emergency cesarean section. 

The primary endpoint, or targeted measure, was a complete TMA response after an initial evaluation period of 183 days, defined as the normalization of platelet count and lactate dehydrogenase (LDH), a marker for red blood cell destruction, and a 25% or greater improvement in serum creatinine, a marker for kidney function.

The analysis showed that seven of the eight postpartum patients (87.5%) met that goal. One patient did not achieve a TMA response, as she did not show the required reduction in creatinine, but had rapid normalization of both platelets and LDH.

The median time to a complete TMA response was 31.5 days, ranging from nine to 46 days, in which all patients demonstrated a rapid normalization of platelet count and LDH levels. The estimated glomerular filtration rate, a kidney function test, also improved from baseline to day 183. 

Finally, all participants initially on dialysis were able to discontinue it within 21 days of starting Ultomiris. 

Headache and fever were the most commonly reported adverse events occurring in at least two of the eight participants. Two patients each reported constipation, urinary tract infection, common cold, hair loss, high blood pressure, joint pain, and increased liver enzymes.

The investigators also determined three possible treatment-related side effects in two patients: non-severe common cold, joint pain, and urinary tract infection, with both patients recovering. One serious event was noted but was unrelated to treatment. No deaths or bacterial infections were reported. 

“In this first prospective interventional trial assessing the efficacy and safety of the long-acting C5 inhibitor [Ultomiris], TMA caused by aHUS was rapidly resolved in the subset of postpartum patients, with continued improvement over time and an acceptable safety profile,” the investigators concluded.

“The results from this subset analysis suggest that [Ultomiris] is effective with a favorable safety profile in women presenting with aHUS postpartum.”