Voydeya safe, effective as single therapy or add-on PNH treatment
Analysis of 4 global trials adds to 'growing body of data' supporting its use
Voydeya (danicopan) — whether given as a single therapy or as an add-on to standard treatment — is safe and effective in treating people with paroxysmal nocturnal hemoglobinuria (PNH).
That’s according to a systematic review and meta-analysis of data from four international clinical trials that tested the PNH treatment in more than 75 people with the rare acquired disease, which is marked by the destruction of blood cells.
The analysis found that treatment with Voydeya increased levels of hemoglobin — the protein that transports oxygen in red blood cells — in patients, and reduced both the levels of reticulocyte, or immature red blood cells, and the need for blood transfusions.
“Our findings provide vital insights into the growing body of data supporting [Voydeya’s] involvement in PNH therapy,” the researchers wrote, noting “there was no evidence of increased infection rates associated with the use of [Voydeya].”
The study, “Safety and efficacy of danicopan in patients with paroxysmal nocturnal hemoglobinuria: a systematic review and meta-analysis,” was published in the journal Expert Review in Hematology.
Voydeya approved in US, Europe this year as PNH treatment
PNH is caused mainly by mutations in the PIGA gene in hematopoietic stem cells — the cells in the bone marrow that are responsible for producing new blood cells. These mutations result in low levels of proteins that normally tag blood cells in a way that the immune system recognizes them as a healthy part of the body.
Without these proteins, a part of the immune system called the complement cascade is abnormally activated and leads to the destruction of red blood cells, a process known as hemolysis. PNH symptoms include anemia — low levels of red blood cells or of hemoglobin — blood in the urine, and fatigue.
Voydeya was approved earlier this year, both in the U.S. and in the European Union, as an add-on treatment to standard PNH therapies to help control extracellular hemolysis, which occurs outside blood vessels. Specifically, the treatment was approved for use with the approved therapies Soliris (eculizumab) and Ultomiris (ravulizumab).
While all three therapies target the complement cascade, Voydeya suppresses a complement protein, called factor D, that acts upstream of Soliris’ and Ultomiris’ target in the cascade of complement activation.
By blocking this protein, the therapy can reduce extracellular hemolysis without interfering with the activity of Soliris or Ultomiris, which are particularly effective at controlling hemolysis within blood vessels.
To learn more about Voydeya’s safety and efficacy in PNH patients, a team of researchers in Turkey systematically reviewed studies published through January of this year. A total of four global clinical trials — three Phase 2 studies and one Phase 3 trial — were used in the analysis.
The studies enrolled a total of 79 patients, 58.2% of whom were women.
One Phase 2 study, ACH471-100 (NCT03053102), evaluated the safety and efficacy of Voydeya as a single therapy for 84 days in 10 untreated patients. That trial’s extension Phase 2 study (NCT03181633) is assessing the therapy’s long-term effects in eight of those patients for about three years.
Another Phase 2 trial, ACH471-101 (NCT03472885), tested Voydeya, given for six months, in 12 patients previously treated with Soliris.
In the Phase 3 trial, dubbed ALPHA (NCT04469465), a total of 73 patients already being treated with Soliris or Ultomiris were randomly assigned to receive either Voydeya or a placebo for 12 weeks, or about three months. Voydeya was given to 49 participants, while the other 24 received the placebo.
2 of 4 studies showed therapy reduced need for blood transfusions
Pooled data from all four studies showed that Voydeya significantly increased blood hemoglobin levels after 12 weeks of treatment, with a high variability across studies in terms of the effect size. Meanwhile, blood levels of reticulocytes, or immature red blood cells, were consistently and significantly decreased, indicating reduced hemolysis.
Results from three studies demonstrated that blood levels of bilirubin, a marker of hemolysis, were significantly decreased after Voydeya treatment. However, blood levels of another hemolysis marker, lactate dehydrogenase — which was assessed in all of the studies — showed no significant differences after the 12 weeks.
Data from the four studies showed that treatment with Voydeya significantly eased fatigue, as assessed by the patient-reported Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue Scale.
Finally, two studies demonstrated that treatment reduced the need for blood transfusions. Specifically, in the Phase 3 trial, 83% of the patients receiving Voydeya remained free from blood transfusions, compared with 38% of those in the placebo group.
A total of 64 adverse events were identified across the studies, with an estimated occurrence rate of 90.4%. The majority were minor, including cough, headache, common cold, fatigue, abdominal pain, and nausea. Seven serious adverse events occurred, but all were deemed unrelated to treatment.
“There was no evidence of increased infection rates associated with the use of [Voydeya],” the researchers wrote.
Our systematic review and meta-analysis support the potential of [Voydeya] as a viable therapy for PNH patients.
Voydeya “was mainly studied in three studies as an add-on therapy to [Soliris] or [Ultomiris], however, one study investigated its effectiveness as a monotherapy [or single therapy] treatment,” and it “demonstrated adequate safety and comparable efficacy when used as a monotherapy,” the team wrote.
Overall, according to the researchers, “our systematic review and meta-analysis support the potential of [Voydeya] as a viable therapy for PNH patients.”
The team called for additional studies to further test Voydeya in PNH patients.
“Future research should focus on larger, longer-term trials to establish the efficacy and safety of [Voydeya], potentially increasing its therapeutic relevance and impact on patient outcomes in the treatment of PNH,” the researchers wrote.
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