Individually dosed Empaveli more convenient, less costly in PNH

Regimen may allow a larger interval between doses in about 30% of adults

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Individualized dosing of Empaveli (pegcetacoplan) may allow for a larger interval between doses in about 30% of adults with paroxysmal nocturnal hemoglobinuria (PNH), while cutting costs by about 8%, according to a study that simulated a clinical trial.

The study, “Development of a target concentration intervention to individualize paroxysmal nocturnal hemoglobinuria treatment with pegcetacoplan,” was published in Annals of Hematology by researchers in the Netherlands.

Complement proteins act in a cascade, where one protein activates the next, to help the immune system fight off infection. In PNH, they become overactive, driving the destruction of red blood cells.

Empaveli, an inhibitor of the C3 complement protein that’s sold as Aspaveli in Europe, is approved in the U.S. for adults with PNH who’ve never been treated before or are switching from Soliris (eculizumab) or Ultomiris (ravulizumab). Both medicines are approved PNH treatments that target C5, another complement protein.

In Europe, Aspaveli is approved for adults with PNH who continue to have anemia, or low levels of red blood cells, despite treatment with a C5 inhibitor for at least three months. Inhibiting C3 should prevent red blood cells from breaking down, easing PNH symptoms.

While Empaveli isn’t as expensive as Soliris or Ultomiris, it still comes with an estimated price of nearly $500,000 per patient per year at the recommended dose of 1,080 mg twice weekly.

“An individualized dosing strategy might be useful to improve patient-friendliness and cost-effectiveness,” wrote the researchers, who developed a model based on how the medication works and how it’s processed in the body to try to come up with such a strategy.

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Proposing a new dosing regimen

In a simulation, they compared the approved 1,080 mg, twice weekly dose with an individualized regimen based on an algorithm for reaching the best, or target, dose in patients who’d never been treated or were switching from Soliris. The simulation was based on data from 1,171 adults with PNH and considered that a Empaveli concentration between 396 and 597 micrograms per milliliter of blood would have a therapeutic effect.

The relationship between the Empaveli concentration and hemoglobin, the protein that carries oxygen in red blood cells, was modeled based on how the medication would work after 16 weeks and how it would move into, through, and out of the body.

For those who’d never been treated with Soliris, trough concentration, or the concentration of Empaveli reached immediately before the next dose was given, varied widely for the approved dose. The individualized regimen only moderately reduced this variability.

While fewer patients would reach a sub-therapeutic concentration of Empaveli with the individualized regimen (3% vs. 1%), median hemoglobin was comparable in both regimens, with a similar proportion of patients having normal-range hemoglobin (45.6% vs. 44.4%).

Similar findings were obtained for lactate dehydrogenase (LDH), a marker of cell and tissue injury. Median LDH was comparable between the two regimens, with about half reaching a normal range LDH concentration.

Individualized dosing would make the interval between doses shorter for 2.3% of patients and longer for 28.2%. Assuming a cost of $4,404 per injection, a dose reduction would cut annual costs by about 4.7%, from $458,000 to $436,358.

Similar results were seen in those who’d been treated with Soliris. The interval between doses would be shorter for 1.4% of patients and longer for 36.7%, and the yearly costs would fall $420,626, an 8.2% reduction.

Individualized dosing based on target concentration could offer benefits, such as improving patient convenience and possibly lowering costs, the study suggests.

The simulation was based on data from patients “with restrictive eligibility criteria and might not entirely be illustrative for the real-world population,” wrote the researchers, who recommended evaluating their proposal in a real-world setting.