New infusion therapy cuts need for blood transfusions in small PNH trial
Nearly 90% saw hemoglobin levels increase with no need for procedure
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Use of an experimental infusion therapy for paroxysmal nocturnal hemoglobinuria (PNH) helped increase the levels of hemoglobin — the oxygen-carrying protein in red blood cells — while reducing the need for blood transfusions among participants in a small trial.
Data show the mid-stage clinical trial testing HSK39297, in the pipeline at Haisco Pharmaceutical Group, met its primary goal, with nearly 90% of participants seeing an increase of at least 20 g/L in hemoglobin levels in the absence of blood transfusions. This was accompanied by improvements in several other blood parameters during the Phase 2 study, the researchers noted.
The team urged further clinical testing of the PNH therapy candidate, highlighting that “transfusion avoidance was achieved by 95.7%” of participants. That means that almost none of the patients needed a transfusion, a procedure in which blood or its components are delivered into the bloodstream.
“The consistent efficacy of HSK39297 across multiple endpoints and its favorable safety profile support its [Phase] 3 development,” the researchers wrote.
The study findings were detailed in a letter to the editor, titled “Efficacy and safety of HSK39297 monotherapy in patients with paroxysmal nocturnal hemoglobinuria,” published in the Chinese Medical Journal. Two of the authors are employees of Haisco, which funded the China-based study.
PNH is an acquired disease characterized by sudden bouts of red blood cell destruction, called hemolysis. As red blood cells break apart, they release hemoglobin. This leads to anemia, or a shortage of red blood cells and/or hemoglobin, which can cause fatigue and other symptoms.
The body’s complement system, a part of the immune system, helps drive hemolysis in PNH. As such, treatment often involves complement inhibitors, particularly those targeting a protein called C5. By targeting this protein to block complement activation, the approved antibody-based therapies Soliris (eculizumab), Ultomiris (ravulizumab-cwvz), and PiaSky (crovalimab-akkz) aim to reduce attacks on red blood cells and, in turn, ease PNH symptoms. These treatments, however, don’t always eliminate anemia.
“Although [C5-targeting antibody] therapies have improved outcomes, many patients remain anemic,” the researchers wrote. This is because of residual hemolysis happening inside blood vessels, as well as hemolysis occurring outside blood vessels. Hemolysis outside blood vessels is largely driven by C3, another complement protein that acts before C5 in the cascade of complement activation.
HSK39297 targets a different protein in the body
HSK39297 aims to avoid this problem by targeting factor B, a protein that regulates C3, and suppressing complement activation at an early point in the complement cascade. One approved medication, Fabhalta (iptacopan), also works this way.
To assess the safety and effectiveness of HSK39297 in people with PNH, Haisco sponsored an open-label, randomized, multicenter Phase 2 trial. In an open-label study, both participants and researchers know the treatment being given patients. The trial enrolled 47 individuals who had never been treated with complement inhibitors and were randomly assigned to receive HSK39297 in one of three possible dosing regimens — two twice-daily and one once-daily — for 24 weeks, or nearly six months.
Across the groups, 89% of participants met the trial’s main goal — an increase of at least 20 g/L in hemoglobin levels from the study’s start to weeks 4-24 in the absence of transfusions. The largest proportion of responders was in the once-daily dosing regimen. The mean change in hemoglobin levels ranged from 48.3 to 51.3 g/L, depending on the dosing regimen.
The team also assessed several secondary outcomes to get a clearer picture of the therapy’s effectiveness. The researchers found that, overall, 96% of participants entirely avoided blood transfusions during treatment with HSK39297. Additionally, participants experienced lower levels of fatigue while taking the medication.
The levels of several hemolysis markers also decreased over the course of the study, the team noted.
Best results seen in trial with once-daily regimen
No hemolysis events occurred during treatment, and no participants experienced blood clotting complications. The most common drug-related side effects were headaches, upper respiratory tract infections, nausea, bacteria in the urine, and increases in the levels of the enzyme alkaline phosphatase, which could indicate liver problems.
All but one of these side effects were mild or moderate. The only severe safety event that investigators deemed to be related to the medication was pneumonitis, a type of lung inflammation, which was resolved with antibiotics.
“Among the three [dosage groups], the … once-daily regimen resulted in the highest primary endpoint achievement, optimal secondary efficacy …, and the lowest incidences of [severe side effects and drug-related side effects], supporting its selection for [Phase] 3 trials,” the team wrote.
The results suggest that HSK39297 may, like Fabhalta, help prevent hemolysis occurring inside and outside blood vessels. However, Fabhalta requires twice-daily dosing. HSK39297’s potential once-daily dosage could “[improve] convenience and potentially [reduce] missed-dose risks,” the researchers suggested.
Still, the team noted that the trial was relatively short and involved a small group of participants, potentially limiting the analyses. Additionally, there was no control group, which makes it more difficult to definitively attribute changes to HSK39297.
Haisco sponsored two Phase 3 studies in China — NCT06799546 and NCT07052838 — to test HSK39297’s once-daily dosing regimen. Results from these studies, along with an ongoing open-label extension study (NCT06745622), are expected to provide more information about the effectiveness and safety of HSK39297 for PNH.
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