Introduction
Fordadistrogene movaparvovec (FM) (PF-06939926) is an investigational product being developed for Duchenne muscular dystrophy (DMD), a recessive disease with progressive loss of muscle mass and function. The objective was to characterize natural disease progression and treatment effects of FM in ambulatory DMD participants using North Star Ambulatory Assessment (NSAA) total scores (TS). The influence of potential covariates on disease progression was also evaluated.
Materials & Methods
Data from four studies (NCT00468832; NCT03760029, NCT02310763, NCT01865084) were used to describe natural disease progression and treatment effects were evaluated using data from an open-label FM study (NCT03362502). A modified, indirect response disease progression model as a function of age with kin and kout terms to describe the upward and downward trajectory of NSAA TS was developed. The magnitude of treatment effect was estimated as a fraction of kout. The influence of covariates on disease progression was evaluated using stepwise covariate modeling. Simulations were performed to compare change from baseline (CFB) at 1 year with and without FM treatment.
Results
The model adequately described the data with a shallower slope for NSAA TS after FM administration compared with natural disease progression (Treatment was 87.5% of kout Control). Mean (±SD) CFB in NSAA TS at 1 year was 0.464±8.13 for control vs. 2.69±4.62 for FM for baseline age 6-<8 years and -2.07±8.51 for control vs. -0.268±5.48 for FM for baseline age ≥ 8 years. Baseline 10-meter run/walk velocity was a significant covariate on kout and kin. Median simulated CFB at 1 year was greater following FM administration compared with natural disease progression, and higher for younger (6 - < 8 years old) than older (≥ 8 years old) baseline ages.
Conclusion
The indirect response model described the data well, predicting slower disease progression following FM treatment particularly for younger participants.