Alexion's Ultomiris Gains aHUS Indication in Japan

Alexion’s follow-on ravulizumab product (Ultomiris) has received marketing authorization from Japan’s Ministry of Health Labor and Welfare for treatment of adults and children with atypical hemolytic uremic syndrome (aHUS).

Ultomiris is Alexion’s advance on its reference eculizumab (Soliris) product, which faces biosimilar competition. The company is currently awaiting final authorization from the European Commission for a new formulation of Ultomiris that received a recommendation earlier this month from Europe’s Committee for Medicinal Products for Human Use (CHMP).

aHUS is a very rare disease that causes progressive harm to the kidneys and other vital organs by damaging blood vessel walls and causing blood clots. Ultomiris is a long-acting C5 inhibitor that is administered every 2 months for adults and children weighing at least 20 kg. The C5 protein is part of the body’s complement system, which stimulates the clearance of microbes and damaged cells from the body. Excess C5 activation can lead to damaging inflammation.

Nature of aHUS

“The goal of aHUS treatment is to prevent the body from attacking its own immune system through inhibition of uncontrolled C5 complement activation,” Shoichi Maruyama, director of the Department of Nephrology, Nagoya University Hospital, Japan, said in a statement. “Importantly, Ultomiris demonstrated good control, while also offering more time between infusions, which provides a relevant difference to patients and providers.”

Many patients present with aHUS in the hospital setting and require supportive care, including dialysis, in the intensive care center. The prognosis for these patients is often poor, and with supportive care alone, 56% of adults and 29% of children will develop end-stage renal disease or die within a year of disease diagnosis, so a timely and accurate diagnosis in addition to treatment, is critical to improving patient outcomes. In 2 single-arm, open-label studies, ravulizumab demonstrated improved kidney function and normalization of hematologic measures including platelet count and lactate dehydrogenase (LDH).

In initial treatment periods (26 weeks), 54% of adults and 77.8% of children demonstrated complete thrombotic microangiopathy (TMA) response. Normalization of LDH was recorded in 77% of adults and 90% of children. Platelet count normalized in 84% of adults and 94% of children. Improved kidney function was observed in 59% of adults and 83% of children.

In the 52-week follow-up, an additional 4 adults and 3 pediatric patients had a complete, confirmed TMA response. The overall complete TMA response was 61% for adults and 94% for children.

Alexion also reported that a cohort of 10 pediatric patients with a history of eculizumab treatment experienced disease control with ravulizumab, demonstrating that switching from eculizumab “maintained disease control as evidenced by stable hematologic and renal parameters, with no apparent impact on safety.”

Adverse events of highest frequency noted were upper respiratory tract infection, diarrhea, nausea, fatigue, headache, nasopharyngitis, and pyrexia.