Criteria for Gene Therapy Trials Can Exclude Many With Severe Hemophilia

Aisha I Abdullah PhD avatar

by Aisha I Abdullah PhD |

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gene therapy trials and participation

Screening for clinical trials in gene therapy can exclude the vast majority — 92% — of severe hemophilia patients, for reasons too often due to potentially modifiable factors such as socioeconomic status and location, a study of patients at a treatment center in Belgium reported.

Patients’ unwillingness to take part in a gene therapy study was also a factor, but individual hesitancy and trial eligibility criteria should change as gene therapies become more widely accepted, and possibly enter commercial use, its researchers noted.

“Our study demonstrates that in a fairly large cohort of individuals with severe hemophilia, [less than] 10% were motivated and eligible to participate in a clinical gene therapy study,” the team wrote, emphasizing that “hematologists should individually assess gene therapy benefits for each patient and regularly inform them about advances in gene therapy.”

The study, “Patient selection for hemophilia gene therapy: Real‐life data from a single-center,” was published in Research and Practice in Thrombosis and Haemostasis.  

Several clinical trials are currently underway into potential gene therapies for hemophilia. These therapies work to induce the production of coagulation factors VIII and IX, which promotes normal blood clotting and are deficient in hemophilia A and hemophilia B, respectively.

Patient eligibility for gene therapy trials is based on rigorous screening criteria that can exclude potential participants for a variety of factors, including age, sex, and comorbid conditions (other health conditions apart from hemophilia). Other criteria, such as lack of motivation to participate in a trial or fear, location, and socioeconomic barriers, might also be overcome or modified to improve participation.

Researchers assessed gene therapy trial eligibility in a group of people with severe hemophilia being treated at a large hemophilia center in Brussels to determine if and why they may be excluded from the studies. 

A total of 87 adults were included in the analysis — 75 with severe hemophilia A and 12 with severe hemophilia B.

Of those, 11 patients (12.6%) who were 65 or older were excluded due to their age, and two female patients (2.3%) were excluded due to their sex. The presence of antibodies that attack coagulation factors VIII or IX prevented another six (6.9%) from taking part, while another patient (1.1%) lacked sufficient exposure to coagulation factor VIII.

Five other patients (5.7%) were excluded because of uncontrolled comorbidities (such as heart disease), one (1.1%) for active hepatitis C infection, and two (2.3%) for alcohol abuse.

Of those remaining, seven (8%) patients were also excluded due to distance from the trial site, language barriers, socioeconomic issues, or major disability making study participation burdensome.

Of the initial 87 patients, 50 (57.5%) were interviewed about potential participation in a gene therapy trial. Fourteen (16.1%) agreed to enter the screening process, while 29 (33.3%) declined, and seven (8%) were excluded due to cognitive difficulties, unreliability, unwillingness to participate, or socioeconomic issues and travel distance.

Nearly half of all patients analyzed (43 people, 49.4%) were excluded from participating in a gene therapy trial due to potentially modifiable factors, the study noted.

“The majority of individuals with severe hemophilia could not be enrolled in gene therapy trials, almost half of them because of partly modifiable psychosocial reasons,” the researchers wrote.

Of the 14 patients who agreed to be screened for the gene therapy, six had neutralizing antibodies that would negatively affect gene therapy delivery, and one had signs of liver fibrosis. 

In total, 8% of the initial patient group — seven out of 87 — were eligible for a gene therapy trial. 

Without the strict screening criteria for clinical trial participation, an estimated 41.4% (36 out of 87 patients) would have accepted gene therapy.

“Although the vast majority of individuals with hemophilia with severe disease at our [center] could not be enrolled in gene therapy trials, the proportion of individuals who may actually undergo gene therapy is likely to significantly increase in the future, given that eligibility criteria will change upon commercialization of products,” the researchers wrote.

“We emphasize that almost half of our patient cohort was excluded primarily due to psychosocial factors, some of which are clearly modifiable, thus constituting leverage points that are able to increase gene therapy adoption. Solid scientific evidence on long‐term gene therapy efficacy and safety is urgently needed to extend its availability and adoption to a broader population of individuals with hemophilia,” the team concluded.