Real-world analysis supports effectiveness, safety of Ultomiris

As part of study, researchers analyzed safety data from 218 people in Japan

Marisa Wexler MS avatar

by Marisa Wexler MS |

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A person sits on a hospital bed whil receiving an intravenous infusion, which hangs on a pole nearby.

When used in real-world practice to treat paroxysmal nocturnal hemoglobinuria (PNH), the safety and effectiveness of Ultomiris (ravulizumab-cwvz) is similar to what’s been reported in clinical trials, according to a recent study from Japan.

“These real-world data support the safety and effectiveness of [Ultomiris] treatment in Japanese patients,” the researchers wrote in “Interim analysis of post-marketing surveillance of ravulizumab for paroxysmal nocturnal hemoglobinuria in Japan,” which was published in the International Journal of Hematology. The study was sponsored by Alexion Pharmaceuticals, a subsidiary of AstraZeneca, which markets Ultomiris.

The therapy is approved for PNH and works by blocking the activation of the complement system, a group of immune proteins whose overactivation destroys blood cells. It works virtually the same as Soliris (eculizumab), another approved PNH treatment also developed by Alexion. Ultomiris is designed to be more stable and last longer in the body, however, enabling it to be given less frequently. Ultomiris maintenance infusions are typically given once every two months. Soliris must be infused every two weeks.

Ultomiris was approved for PNH in Japan in 2019. As mandated by regulators, a postmarketing surveillance program has been collecting data on people treated with Ultomiris since its approval. In this study, scientists reported data collected by the surveillance program between 2019-2021. The analysis included safety data on 218 people with PNH who’d been treated with Ultomiris. Most had switched from Soliris to Ultomiris.

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Side effects, safety findings of Ultomiris

Over a median follow-up of 74.4 weeks (about 1.5 years), 193 side effects were reported in 66 (30.3%) patients. Anemia and fever were each observed in 3.7% of patients.

The real-world safety findings for Ultomiris were generally consistent with what’s been reported in clinical trials. Infections, a known risk with medicines like Ultomiris that work by lowering immune system activity, were reported in 8.7% of the patients, but most weren’t serious.

In clinical trials, the most common side effect was headache, but only one patient reported a headache in this analysis. This might be because some patients had a mild headache that wasn’t recorded by the surveillance study or it might be because headache usually occurs when patients are first starting complement-blocking treatment, which was not the case here, as most had already been taking Soliris before switching.

Four deaths were recorded during the study. Two were conclusively determined to be unrelated to Ultomiris. In the other two cases, a possible role of the medication “could not be ruled out.” Both deaths occurred in elderly patients who had multiple co-occurring health problems. One died from an infection (pneumonia) and the other from worsening PNH and kidney problems.

“The [adverse events] observed in this study were consistent with those reported in the clinical trials and the overall safety profile was acceptable,” the researchers wrote.

Data from those who switched from Soliris to Ultomiris showed the levels of lactate dehydrogenase (LDH), a marker of blood cell destruction, were generally stable over the switch and with continued treatment. Hemoglobin, the protein that red blood cells use to carry oxygen through the body, was also stable.

In the dozen or so patients who started Ultomiris without previous treatment, LDH levels decreased and hemoglobin levels increased, consistent with the therapy’s ability to prevent blood cell destruction.

In the 185 patients with a history of blood transfusions, most (79.5%) didn’t require a transfusion over six months with Ultomiris. Patients with bone marrow failure, meaning bone marrow can’t produce enough new blood cells, were more likely to require transfusions even while on Ultomiris.

The effectiveness data from the real-world analysis was also consistent with the clinical trial findings, the researchers said.

“Further follow-up data from this [postmarketing surveillance program] will help to elucidate the long-term clinical safety and effectiveness of [Ultomiris] for treating PNH,” they wrote.