Sarepta Therapeutics : P.113 Szabo et al. NSAA & HUI Scores Weakly Correlated Among Boys with DMD

• ▪ DMD is a rare, progressive 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) (a) utility and (b) NSAA total score by visit. Whiskers represent 95% confidence intervals.

  Figure 3. Correlation of NSAA scores with particular HUI attribute scores across all visits

  • ▪ Analyses

    • ▪ Baseline characteristics of the sample were summarized.

• ▪ There are numerous measures to quantify disease progression in DMD, including the NSAA, a 14-point functional assessment scale that documents performance on activities such as walking, running, and stair climbing.

  • ▪ Mean baseline and change over time scores were computed and the correlation between HUI2 and HUI3 utility, and NSAA, at baseline and 48 weeks was calculated using Spearman's coefficient. 6

    • ▪ These relationships were also explored visually.

• ▪ The relentless, progressive functional loss in DMD dramatically affects health-related quality-of-life (HRQoL).

  • ▪ The analyses were also conducted for each HUI attribute individually with NSAA score.

• ▪ 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 cost-effectiveness evaluations of new therapies.

  • ▪ 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).

    • ▪ Among this sample of ambulatory boys with DMD, NSAA is not strongly correlated with overall HUI utility.

      • ▪ However, data on utility scores in DMD are limited, and the relationship between function and utility is unclear.

  • ▪ Mean (SD) baseline HUI3 utility was 0.82 (0.19) and HUI2 utility was 0.87 (0.13).

    • ▪ Visual inspection of scatterplots revealed potentially inconsistent combinations of scores which would have impacted the correlation between the two measures:

  • ▪ Mean change over 48 weeks (Figure 1) was -0.06 (0.19; HUI3, n=57), -0.05 (0.14; HUI2, n=54), and -2.9 (4.7; NSAA, n=58).

  • ▪ Patients with high HUI scores and low levels of function, and

    • ▪ Visual inspection of the relationships between NSAA and HUI scores demonstrates the presence of outliers; individuals with low levels of function but with high utility, and individuals with good physical functioning but low utility.

  • ▪ Patients with large variability in utility at the same levels of NSAA function.

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

  • ▪ For example, 4 patients with relatively stable NSAA had large changes in utility due to deteriorations in emotion (1 patient dropped 2 levels), pain (3 patients dropped 1 level), cognition (1 patient dropped 2 levels and another, 3 levels), vision (1 patient dropped 3 levels), and speech (1 patient dropped 1 level).

  • ▪ It is important to note that there were stronger correlations with individual domains including ambulation, mobility, and ability for self-care.

  • ▪ Limitations include the small sample size and limited follow up over which to assess change in utility and functional status.

  CONCLUSIONS

  Figure 2. Scatterplots of change (week 48 - baseline) in NSAA score vs change in HUI utility with a best-fit line

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

  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.

  While NSAA score is correlated with the ambulatory components of the HUI, additional important drivers of utility exist. Functional status alone cannot explain HUI utility estimates in ambulatory DMD patients. In clinical trials, it is therefore important to consider both measures as they evaluate different and meaningful concepts.

• ▪ Patients were followed over 48 weeks and NSAA, timed rising from floor (RFF) and 10-meter walk/run (10MWR) tests were assessed at baseline and every 12 weeks by trained assessors.

  *n=55

• ▪ 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.

  • ▪ Weak positive correlations were observed between baseline NSAA score and utility (HUI3: r=0.17; HUI2: r=0.29), and over 48 weeks (HUI3: r=0.15, HUI2: r=0.16; Figure 2)

    • 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.

    • 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. Cohen, Statistical Power Analysis for the Behavioral Sciences,

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

• ▪ Moderate positive correlations were observed between NSAA score and the HUI3 ambulation (r=0.41), HUI2 mobility (n=0.41), and HUI2 self-care (r=0.42) scores; NSAA scores were weakly correlated with HUI3 pain (r=-0.20; Figure 3).

• 2nd Ed. 1988.

ACKNOWLEDGEMENTS & DISCLOSURES

This study was funded by Sarepta Therapeutics. IA and KG are employees of Sarepta. SMS, BR, and KJ 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

Correlation analysis between Health Utilities Index (HUI) and the North Start Ambulatory Assessment (NSAA) scores in Duchenne muscular

Dystrophy

Szabo SM,1 Audhya I,2 Rogula B,1 Feeny D,3 Johnston K,1 Gooch KL.2

1Broadstreet HEOR, 201 - 343 Railway St, Vancouver BC Canada; 2Sarepta Therapeutics, 215 First St, Cambridge MA 02142 USA; 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)