A subset of patients with hemophilia A who received gene therapy with dirloctocogene samoparvovec in a phase 1/2 trial demonstrated signs of improved joint health. In addition, some patients reported better function and resolution of target joint support, according to data presented at the International Society of Thrombosis and Haemostasis (ISTH) 2023 Congress.

The phase 1 portion of the trial evaluated 4 dose levels of a single infusion of dirloctocogene samoparvovec in 24 patients with moderate or severe hemophilia A (ClinicalTrials.gov Identifiers: NCT03003533, NCT03432520).

It was previously reported that dirloctocogene samoparvovec reduced the annual bleeding rate by 82% for patients receiving FVIII prophylaxis and 99% for patients receiving on-demand therapy. This report was of an exploratory analysis of joint health.

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Joint health was evaluated at baseline and multiple times throughout the study using the Hemophilia Joint Health Score (HJHH) v2.1 in the knees, ankles, and elbows. Self-perceived function was measured by the Hemophilia Activities List (HAL) score, which included domains of function of extremities, and the ability to do household tasks, leisure activities and sports, changing body position, self-care, and use of transportation.

At baseline, the median age of the patients was 33.5, with 91.7% who were White and 8.3% were Black/African American. There were 91.7% of patients with severe hemophilia, and 79.2% of patients were taking FVIII prophylaxis with the remaining using on-demand therapy. There were 29.2% of patients with at least 1 target joint, which was defined as a single major joint with a minimum of 3 spontaneous bleeds that occurred within 6 months.

Of the 5 patients with a target joint and sufficient follow-up, all had resolved such that there were 2 or fewer bleeds in the joint during the period of 1 year. There were no new target joints during the study.

Dirloctocogene samoparvovec resulted in what was considered a clinically meaningful improvement in HJHS scores from baseline, with a mean improvement of 4.1 and 6.4 in year 2 and 3, respectively. HJHS score improvement occurred among patients with or without a target joint at baseline.

Of the joints evaluated for joint pain, the elbow showed modest to no improvement in self-reported pain by year 3. Ankles showed modest improvement, whereas knees showed the most improvement.

Self-perceived function, as indicated by HAL score, also improved with dirloctocogene samoparvovec, with most patients demonstrating an improvement by year 1 that was maintained through year 3.

“Based on these exploratory analyses, clinically meaningful improvements in joint health were observed in a subset of people with hemophilia A,” the study’s presenter concluded.

Disclosures: This research was supported by Spark Therapeutics, Inc. Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.


Samelson-Jones B, Cygan P, Croteau S, et al. Improved joint health after gene therapy with dirloctocogene samoparvovec (SPK-8011) in people with hemophilia A. ISTH 2023 Congress. June 24-28, 2023. Abstract OC 20.3.