PNH patients on Soliris or Ultomiris rarely die from disease itself: Study

Bone marrow failure is major cause of life-threatening health problems

Marisa Wexler MS avatar

by Marisa Wexler MS |

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Treatment with Soliris (eculizumab) or Ultomiris (ravulizumab) can substantially reduce the likelihood of death as a direct result of paroxysmal nocturnal hemoglobinuria (PNH), a new study found.

While the findings showed that PNH itself is rarely fatal for people taking these therapies, co-occurring bone marrow failure remains a major cause of life-threatening health problems for many patients with the rare acquired disease.

Overall, the researchers noted that Soliris and Ultomiris are “effective, well-tolerated therapies for patients with PNH, and the risks of complications are low.”

Their study, “Treatment outcomes of complement protein C5 inhibition in 509 UK patients with paroxysmal nocturnal hemoglobinuria,” was published in the journal Blood.

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Real-world analysis supports effectiveness, safety of Ultomiris

About half of Soliris patients switched to Ultomiris after therapy’s approval

Soliris was the first therapy for PNH to win widespread approval. Ultomiris is a newer treatment that works similarly, but is administered less frequently — every one or two months instead of every other week.

Both medications work by targeting C5, a protein that’s part of the complement cascade — a series of immune proteins whose activation drives blood cell destruction in PNH.

Soliris and Ultomiris are both marketed by Alexion, AstraZeneca Rare Disease, the group within AstraZeneca focused on rare disorders. It was created in 2021 after the company acquired Alexion Pharmaceuticals.

In this study, a team of scientists that included several consultants for AstraZeneca/Alexion reviewed the outcomes of 509 people with PNH in the U.K. who received treatment with Soliris and/or Ultomiris during the two decades between May 2002 and July 2022.

“To our knowledge, this retrospective study is the largest analysis of patients receiving [Soliris and/or Ultomiris] over a prolonged period of time in this ultrarare condition,” the researchers wrote.

For all patients, the median time from first experiencing PNH symptoms to receiving a correct diagnosis was about five months. The researchers noted, however, that more than 1 in 3 patients waited more than a year before getting a proper diagnosis. Moreover, more than 1 in 10 were misdiagnosed with other disorders before being correctly diagnosed with PNH.

About half of the patients in the analysis had a history of bone marrow failure, which occurs when the bone marrow isn’t able to produce enough new blood cells.

Additionally, more than a quarter of the patients had experienced thrombotic events before starting treatment with Soliris and/or Ultomiris. Thrombotic events are caused by blood clots that obstruct blood flow, and historically have been a leading cause of fatal complications in people with PNH.

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Soliris, Ultomiris treatment fails most PNH patients in real world

Infection was leading cause of death among PNH patients in study

More than 90% of the patients started treatment with Soliris, and about half of these switched to Ultomiris when the newer medicine became available in the U.K. There also were a handful of recently diagnosed patients who were started on Ultomiris without ever taking Soliris.

Over the course of the study period, 91 patients died. The leading cause of death was infection, which accounted for more than one-third of these deaths. Meanwhile, four patients died due to thrombosis while on Soliris and/or Ultomiris.

This data show that, although life-threatening thrombotic events can still occur in patients taking these medications, “for the most part, patients are no longer dying from their PNH,” the researchers wrote.

For the most part, patients are no longer dying from their PNH.

Survival data showed that, compared with the general U.K. population, people with PNH on Soliris and/or Ultomiris had a significantly lower likelihood of survival at 10 or 20 years after starting treatment.

However, these differences weren’t significant when researchers excluded patients with bone marrow failure from the analysis. This suggests that other PNH-associated complications, and not PNH itself, may be linked to the reduced likelihood of survival in patients on these therapies.

“Although the [overall survival] of all the patients treated over the 20-year period was not equal to that of age- and sex-matched controls, we believe the difference in [overall survival] is due to the underlying [bone marrow failure],” the researchers wrote.

The team noted that “when patients with either progression of their [bone marrow failure] or those receiving treatment for their [bone marrow failure] are excluded, the [overall survival] is not significantly different from that of age- and sex-matched controls.”

Based on these findings, the team highlighted the need for further studies focused on how best to improve care specifically in patients with PNH who have bone marrow failure.

“Further study into patients who are symptomatic from both PNH and [bone marrow failure] is needed, because the major cause of mortality was related to underlying [bone marrow failure] and not PNH,” the researchers wrote.