Sarepta Therapeutics : P.104 Audhya et al. HRQoL with DMD Study Using HUI

BACKGROUND

METHODS, CONT.

RESULTS, CONT.

• ▪ DMD is a rare X-linked neuromuscular disorder caused by mutations in the gene for dystrophin.1,2

  • ▪ Progression in DMD leads to loss of ambulation (LOA) in the early teenage years, cardiomyopathy and respiratory insufficiency by early adulthood, and early mortality from late teens into the third decade of life.3-5

  • ▪ The HUI2 system includes seven attributes: sensation, mobility, emotion, cognition, selfcare, pain, and optionally, fertility (not assessed).

  Figure 1. Mean (SD) HUI3 and HUI2 utility by visit stratified by baseline age. Whiskers represent 95% confidence intervals.

  • ▪ Mean (SD) utility values from the exploratory analyses were:

    • ▪ In terms of analysis

      • ▪ Lowest among those in the lowest quartile of NSAA score (HUI3: 0.73 (0.28), HUI2: 0.78 (0.15)) and similar among patients in the higher quartiles.

        • ▪ Baseline characteristics of the sample were summarized.

• ▪ Due to its severity, it is not surprising that the progression of DMD dramatically affects the HRQoL of patients and their caregivers.

  • ▪ Mean (standard deviation [SD]) HUI3 and HUI2 utility values were calculated at baseline and 48 weeks; and presented according to ambulatory status and age.

    • ▪ Generally higher among those with higher (better) 10MWR grading codes or RFF grading codes.

    • DISCUSSION

• ▪ Utility scores, values anchored between 0 (dead) and 1 (full health), reflect preferences for the HRQoL implications of specific health states; these are required inputs in the cost-effectiveness evaluations of new therapies.

  • ▪ Among patients with LOA, mean (SD) utility values were calculated across patient-visits post-LOA

  • ▪ Factors associated with changes in utility were explored by comparing mean attribute scores at baseline vs. after LOA.

  • ▪ Among this sample with DMD, utility scores were higher for both ambulant and non-ambulant boys, compared to published HUI3 and HUI2 estimates; there was considerable variability in utility scores.

• ▪ Published utility values for DMD are relatively scarce and are available for only a few health states.6

  • ▪ Mean baseline utilities for ambulant boys were 0.82 (HUI3) and 0.87 (HUI2); and 0.35 (HUI3) and 0.52 (HUI2) after LOA;

• ▪ As existing utility data derive from cross-sectional surveys, longitudinal estimates from clinically well-characterized samples are unavailable.

  • ▪ Published estimates for ambulant boys range from 0.65-0.75; and for non- ambulant boys from 0.05 to 0.44.6

  • ▪ At baseline the mean (range) age of the 61 ambulant boys was 8.0 (5-16) years and mean (SD) NSAA score was 21 (8) (Table 1).

  • ▪ Baseline utility values tended to be higher among those with higher scores on functional assessments.

    Table 1. Characteristics for DMD population (n = 61)

    • ▪ Mean (SD) baseline HUI3 utility was 0.82 (0.19) and HUI2 utility was 0.87 (0.13); values were similar between younger and older boys (Figure 1).

      • ▪ The lack of a linear relationship between functional measures and utility suggests that additional drivers of utility exist beyond motor function.

    • ▪ At 48 weeks, mean (SD) HUI3 utility was 0.75 (0.22) and HUI2 utility was 0.81 (0.18); mean utility had dropped more among older vs. younger boys (Figure 1).

  • ▪ While the utility of younger boys remained relatively stable over time, older boys and those losing ambulation experienced important declines over follow-up.

    METHODS

    • ▪ Six boys (9.8%) lost ambulation over the 48-week period; the mean (SD) utility across patient-visits after LOA was 0.35 (0.15) for HUI3 and 0.52 (0.05) for HUI2, based on a mean decline in utility of 0.25 for HUI3 and 0.18 for HUI2.

  • ▪ Limitations include the small sample size, particularly of those experiencing LOA, and limited follow up over which to assess change in utility.

  CONCLUSIONS

• ▪ Data from placebo-treated ambulant boys with DMD with exon 51 skip amenable mutations, recruited under NCT01254019 (provided by BioMarin Pharmaceuticals Inc), were included.

  • ▪ Change in ambulation levels explained 88% of the drop in HUI3 utility after LOA, while change in emotional status explained 11%.

  6MWD = six-minute walk distance; NSAA = North Star Ambulatory Assessment; RFF = rise from floor; SD = standard deviation. The NSAA is a 17-item instrument with potential scores ranging from 0-34; lower scores indicate a higher degree of functional impairment.

  *n=55

  • ▪ Exploratory analyses were conducted to understand the impact of other patient characteristics on utility at baseline (Figure 2).

  Figure 2. Mean (SD) HUI3 and HUI2 utility at baseline by (a) NSAA score, (b) 10MWR grading code, and (c) RFF grading code. Whiskers represent 95% confidence intervals.

• ▪ Patients were followed over 48 weeks and North Star Ambulatory Assessment (NSAA), timed rising from floor (RFF) and 10-meter walk/run (10MWR) tests were performed at baseline and every 12 weeks.

  Findings from this study help identify potential factors that may impact health state utility in DMD. In addition to motor function, other aspects of HRQoL that may also be important include dexterity, ability for self-care, and pain. These data also help add to the growing body of evidence, by better defining utility values for ambulant boys with DMD.

  • 1. Wein et. al., Pediatr Clin N Am. 2015;62(3):723-742.

    • 4. Yiu et. al., J Paediatr Child Health 2015;51(8):759-764.

• ▪ Family members serving as proxy respondents also completed the 15-item HUI questionnaire, a preference-based utility measure, at baseline, week 24, and week 48.

  • 2. Crisafulli et al., Orphanet J Rare Dis. 2020;15(1):141.

    • 5. McDonald et al., Muscle Nerve. 2013;48(1):32-54.

  • 3. Birnkrant et al., Lancet Neurol. 2018;17(3):251-267.

  • 6. Szabo et al., Qual Life Res. 2020;29(3):593-605.

  ACKNOWLEDGEMENTS & DISCLOSURES

  • ▪ The HUI3 system considers eight attributes: vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain.

*10MWR grading codes range from 1 (Unable to walk independently) to 6 (Runs and gets off both feet off the ground [with no double stance phase]); RFF grading codes range from 1 (Unable to stand from supine, even with use of a chair) to 6 (Stands up without rolling over or using hands]); NSAA scores range from 0 to 34 and are calculated as a sum of 17 activity grades, each ranging from 0 (Unable to achieve independently) to 2 (Normal - no obvious modification of activity).

This study was funded by Sarepta Therapeutics. IA and KG are employees of Sarepta. SMS and BR are employees of Broadstreet HEOR, which received funds from Sarepta to conduct this study. DF received consulting fees related to this work and has a proprietary interest in Health Utilities Incorporated, Dundas, Ontario, Canada. HUInc. distributes copyrighted Health Utilities Index (HUI) materials and provides methodological advice on the use of HUI. Contact:[e-mail]

CONFIDENTIAL - FOR INTERNAL USE ONLY

Presented at the MDA 2021 Virtual Congress March 15 - 21, 2021

Health-related quality of life (HRQoL) associated with Duchenne muscular dystrophy (DMD): A study using the Health Utilities Index (HUI)

Audhya I,1 Rogula B,2 Szabo SM,2 Feeny D,3 Gooch KL1

1Sarepta Therapeutics, 215 First St, Cambridge MA 02142 USA; 2Broadstreet HEOR, 201 - 343 Railway St, Vancouver BC Canada; 3McMaster University and Health Utilities Inc., Hamilton, ON Canada

Mean (SD)
Age, years	8.0 (2.4)
NSAA total score	21.0 (8.1)
6MWD (m)	348 (92)
Timed 10m walk test (s)*	7.5 (3.6)
Timed RFF (s)*	13.4 (15.9)
Unable to RFF, even with use of a chair, n (%)	6 (10)
Unable to RFF independently, n (%)	19 (31)