Hemophilia A Replacement Therapy TQG202 Safely Controls Bleeds: Trial
Preventive treatment found to maintain low bleeding rate
Prophylactic, or preventive, treatment with an experimental replacement therapy called TQG202 safely maintained a low bleeding rate in people with severe hemophilia A.
That’s according to new data from a Phase 3 clinical trial reported in a recent study, which showed TQG202 worked to control bleeds in testing against an approved hemophilia replacement therapy.
“The promising efficacy and tolerability in the prophylactic treatment of severe hemophilia A patients support the use of TQG202 in clinical practice,” the researchers wrote.
The study, “Efficacy, safety and bioequivalence of the human-derived B-domain-deleted recombinant factor VIII TQG202 for prophylaxis in severe haemophilia A patients,” was published in the journal Haemophilia.
The work was funded by Chia Tai Tianqing Pharmaceutical Group, the company developing TQG202.
Hemophilia A is caused by the lack of a blood clotting protein, called factor VIII (FVIII). Replacement therapy is a standard treatment strategy that, as the term implies, involves administering a version of FVIII to replace the dysfunctional protein.
TQG202 is an investigational recombinant (lab-made) replacement therapy that is produced using a human cell line called HEK293.
Assessing TQG202 in trial
The first part of the Phase 3 trial (NCT04061109) aimed to assess the pharmacological properties of TQG202.
It also compared them with those of Xyntha, an approved replacement therapy sold by Pfizer that is produced using a Chinese hamster ovary (CHO) cell line.
This portion of the study enrolled 26 people with hemophilia — each of them male, and with a mean age of 30. The participants were divided into two groups, and given a single injection (50 international units per kilogram of body weight, IU/kg) of either TQG202 or Xyntha. After a four-day-long washout period, designed to remove all medication traces from the body, the participants received an injection of the other therapy. After both injections, blood samples were regularly collected.
Pharmacological analyses of these data broadly showed similar results for both TQG202 and Xyntha. This suggests that the two therapies are bioequivalent, or in other words, that both appear to have a comparable effect on the body.
In the second part of the study, 81 hemophilia A patients were given prophylactic treatment with TQG202, administered three times per week, or every other day, for 24 weeks, or about half a year. All of these patients were male, and had a mean age of 25.9 years.
The initial dose was 30 IU/kg. Dose adjustments were allowed if patients experienced bleeds. On-demand injections of TQG202 also were available to help control bleeding episodes.
During the study period, there were 69 bleeding events, equating to a mean annual bleeding rate of two bleeds per year. The mean rate of joint bleeds was 1.7 events per year.
The median number of bleeds and joint bleeds was zero, meaning the majority of participants did not experience any bleeds during the study.
Researchers noted these bleeding rates are overall “superior to or similar to the other recombinant FVIII products” that are currently used for hemophilia A replacement therapy.
For patients who experienced bleeds, most required either one (45.8%) or two (31.9%) injections of TQG202 to stop bleeding. The rest of the patients — 22.3% — required three or more injections. Three of these patients required more than four injections to stop bleeding.
As an on-demand treatment for bleeds, the majority of participants rated TQG202 as either “good” (65.2%) or “excellent” (18.8%).
Little preventive treatment in China
Over the course of the trial, the mean Hemophilia Joint Health Score (HJHS) decreased from 22.5 to 19.2, indicating an improvement in joint health. Mean scores on the EQ-5D, a measure of overall health status, also improved, increasing from 83.4 to 86.2.
“Use of TQG202 for prophylaxis not only reduce the risk of bleeding, but also further improve the joint function and health status of Chinese severe hemophilia A patients,” the researchers wrote.
Side effects related to the medication were reported in about 20% of the patients, with the most common being heart beat abnormalities. All side effects related to TQG202 were graded as mild or moderate in severity.
Overall, safety data “suggests that TQG202 is tolerable,” the researchers wrote.
The team noted that this study is limited by its relatively small size and short follow-up time. They also noted that all participants in the study had already been on therapy, so further research is needed to assess the safety and effectiveness of TQG202 in patients who have never been treated before.
“Further studies with larger sample size, longer follow-up time and wide population are warranted to support the clinical application of TQG202,” the scientists wrote.
Although several replacement therapies for hemophilia A are approved for use in China, fewer than one in five patients in the country are currently on prophylactic treatment, the researchers noted. This low rate was in part due to difficulties accessing treatments, the team said.
According to the researchers, using TQG202 in clinical practice “might help add treatment options for Chinese patients with severe haemophilia A, alleviating the current shortage of FVIII [replacement therapies] in China.”