Abstracts

Skinner M, Chen E, Kucher A, Germini F, Karimi M, Clearfield E , O’Mahony B , Jain M. Initial results of the impact of valoctocogene roxaparvovec on pain occurrence and interference: Insights from PROBE. (2023), CCS_Book of abstracts. Haemophilia, 29: 3-53. https://doi.org/10.1111/hae.14781

Introduction

People with severe haemophilia A (PwSHA) commonly present with intramuscular bleeding and hemarthrosis, leading to acute and chronic pain with an overall reduction in health-related quality of life. Here, we report the occurrence of pain in PwSHA before and 2 years after administration of valoctocogene roxaparvovec, and its interference on daily life.

Methods

The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire was included in the phase 3, open-label, single-arm study (GENEr8-1) as a tertiary endpoint to assess the effect of a single 6 × 10¹³ vg/kg dose of valoctocogene roxaparvovec on patient-reported health and life experiences. While further validation to understand the performance of PROBE in this context of use is ongoing, this study summarized pain-related outcomes collected within the PROBE questionnaire. This analysis evaluated PROBE completions at baseline and 104 weeks post gene therapy, including any occurrence of acute and chronic pain (recall: 12 months) and during eight activities (walking, stair climbing, nighttime, resting, weight bearing, playing, after falling/trauma, other). Participants also reported pain interference in 11 aspects of life (general activity, mood, walking ability, normal work, attending school, relations with others, sleep, enjoyment of life, playing/participating in sports/exercising, lifting, other). Descriptive statistics including 95% confidence intervals (CI) were presented at baseline and Week 104.

Results

Data were available for 124 participants at baseline and 129 at 104 weeks. Median age was 34 (range 21−73 years). Reporting of acute and chronic pain was reduced post gene therapy (acute pain: 60.5% to 41.9%, chronic pain: 65.3% to 57.0%). At 104 weeks, the aggregate instances of self-reported acute pain occurrence decreased from 151 (15.2%) to 113 (10.9%) across the 8 activities (including ‘Other’) [Table 1]. Chronic pain reduced from 238 (24.0%) to 216 (20.9%) [Table 2]. At 104 weeks, the aggregate instances of self-reported acute pain interference decreased from 294 (21.4%) to 204 (14.4%) across the 11 activities (including ‘Other’) [Table 3]. Chronic pain interference was reduced from 332 (24.3%) to 262 (18.5%) [Table 3 and 4].

Conclusions

Initial analysis of PROBE data demonstrates that gene therapy may be associated with a decrease in self-reported acute and chronic pain occurrence and interference with daily life in the study cohort.  Pain is one of the core outcomes of importance to people with haemophilia. The impact of gene therapy on pain, particularly chronic pain as demonstrated from PROBE, a haemophilia-specific tool, has important implications on treatment decision-making and continued disease management.

Disclosures

Er Chen: Bio Marin Pharmaceutical Inc.; Federico Germini: Bayer Bio Marin Pharmaceutical Inc., Novo Nordisk, Pfizer, Roche, Takeda; Mohit Jain: Bio Marin Pharmaceutical Inc.; Milad Karimi: Bio Marin Pharmaceutical Inc.;

Brian O’Mahony BioMarin Pharmaceutical Inc.CSL Behring; Mark Skinner: Bayer, Bio Marin Pharmaceutical Inc., Blue Cross Blue Shield, ICERMASACNHFNORD, Novo Nordisk, Pfizer, Roche/Genentech, Spark, Takeda, WFH, USA

Oral Presentation: HERE