New study backs approved Voydeya dosing for PNH add-on treatment
Modeling shows doses achieve target complement pathway suppression
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The approved dosing regimens of Voydeya (danicopan) are supported for adults with paroxysmal nocturnal hemoglobinuria (PNH) receiving standard therapies and generally do not appear to require adjustment based on patient characteristics or food intake, according to a new analysis of clinical trial data.
Voydeya is an oral medication approved in the U.S. and other regions as an add-on treatment to Ultomiris (ravulizumab) or Soliris (eculizumab) for adults with PNH. The therapy is typically started at 150 mg three times daily, with the option to increase to 200 mg depending on a patient’s clinical response.
Approvals were primarily based on results from the Phase 3 ALPHA trial (NCT04469465), which evaluated the safety and efficacy of the therapy when added to Ultomiris or Soliris in adults with PNH.
Modeling supports approved Voydeya dosing in add-on PNH treatment
The new findings support that the approved dosing regimens achieve sufficient suppression of the alternative complement pathway involved in red blood cell destruction in PNH. Although factors such as body weight and sex influenced how the drug was processed in the body, and food intake affected how it was absorbed, these differences were not considered clinically meaningful.
“These findings support the approved 150 mg and 200 mg [three times daily] dosing regimens for [Voydeya] in patients with PNH,” the researchers wrote, adding that Voydeya “can be administered regardless of food status.”
The study, “Population PK–PD Modeling of Danicopan Add-On Therapy in Participants With Paroxysmal Nocturnal Hemoglobinuria Treated With Ravulizumab or Eculizumab,” was published in CPT: Pharmacometrics & Systems Pharmacology. The study was funded by Alexion, AstraZeneca Rare Disease, the company that markets Voydeya and also sells Ultomiris and Soliris.
PNH occurs when the complement system — part of the body’s immune defense — mistakenly attacks and breaks down red blood cells in a process known as hemolysis. This can lead to low levels of healthy red blood cells, known as anemia, and symptoms such as shortness of breath, weakness, and severe fatigue.
Standard PNH treatment includes Soliris and Ultomiris, which work by blocking C5, a key protein in the complement system. These therapies are effective at preventing intravascular hemolysis (IVH), the destruction of red blood cells within blood vessels. But they are less effective at controlling extravascular hemolysis (EVH), which occurs when red blood cells are destroyed in tissues outside blood vessels.
Voydeya targets factor D, a protein of the alternative complement pathway that acts upstream of C5 in the complement cascade. As such, Voydeya is expected to prevent EVH without interfering with the activity of Soliris or Ultomiris in controlling IVH.
ALPHA trial showed Voydeya improved anemia, reduced transfusions
Data from the ALPHA trial showed that treatment with Voydeya, given on top of Ultomiris or Soliris, outperformed placebo in controlling anemia and reducing the need for blood transfusions in 86 patients with clinically significant EVH despite treatment with Soliris or Ultomiris. Such benefits were sustained for up to 1.5 years of treatment.
To better understand how Voydeya behaves in the body and to support the approved dosing regimens, researchers built a mathematical model to examine its absorption, processing, and clearance, as well as how the amount of drug circulating in the blood affects its biological activity.
The model was developed using 7,491 blood samples, collected after dosing from 407 participants enrolled in 14 Voydeya trials, including 316 healthy volunteers and 91 people with PNH, along with 478 time-matched measurements of alternative complement pathway activity.
The analysis showed that higher doses of Voydeya led to higher blood drug levels, which, in turn, produced stronger inhibition of the alternative complement pathway. This effect increased with drug levels until it reached a maximum level of inhibition.
Model simulations predicted that both approved dosing regimens produce drug trough concentrations — the lowest drug level in the blood just before the next dose — above the threshold estimated to achieve 90% inhibition of the alternative complement pathway in patients with PNH receiving Soliris or Ultomiris.
Patient factors and food had limited impact on dosing needs
Several factors slightly influenced how the drug was processed in the body. For example, people with higher body weight tended to have lower drug exposure, meaning lower overall drug levels in the bloodstream over time. In contrast, women and people with severe kidney impairment cleared the drug more slowly, resulting in higher drug levels in the blood. Food intake also affected how quickly the drug was absorbed and its peak levels in the bloodstream.
However, the researchers found that none of these factors had a clinically meaningful effect on treatment, meaning they generally do not require dose adjustments, and that Voydeya can be taken regardless of food intake.
These findings “provide evidence to support the current 150mg and 200mg [three times daily] dosing regimens and the drug labeling for [Voydeya] in patients with PNH,” the researchers wrote.
