Switch to Deflazacort Improves Disease Progression in Patients With Dystrophinopathies

Susan Apkon, MD

PTC Therapeutics has announced results from their real-world study of patients with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) who switched from prednisone to deflazacort (Emflaza) treatment.¹

The study found that during the average 6-month follow-up after switching, in patients in which Clinical Global Impression (CGI) scores were available, most disease progression improved or stabilized during steroid treatment, with a shift toward improvement after switching.

"Results from the real-world chart review presented today support the potential of Emflaza to alter the natural history of Duchenne muscular dystrophy, demonstrating its capability to slow progression of the disease and improve benefit-risk," said Susan Apkon, MD, investigator, chief, Pediatric Rehabilitation, vice-chair, Department of Physical Medicine and Rehabilitation, Fischahs Chair in Pediatric Rehabilitation, Children's Hospital of Colorado. "We believe that Emflaza will continue to provide DMD patients a safe and effective treatment option."

Real-World Study of Prednisone to Deflazacort Switch

Results of the real-world study were presented at the Muscular Dystrophy Association’s (MDA) Clinical and Scientific Conference, March 15-18, by Jessica Marden, MPH, PhD, manager, Analysis Group. “Following the approval of deflazacort by the United States Food and Drug Administration for treatment of DMD, an improved understanding of current corticosteroid switching and outcomes in the real-world is needed,” Marden and colleagues wrote.²

Marden and colleagues conducted a chart review that analyzed patients’ characteristics and reasons for switching between February 2017 and December 2018. Altogether, they analyzed data from a cohort including 92 male patients from 55 physicians. 

READ MORE: Ataluren Delays Loss of Ambulation in Patients With Nonsense Mutation DMD

Of these patients, 62 had DMD with a mean age of 6.2 years at switch and an average treatment duration of 2.66 years (standard deviation [SD], 3.2) with prednisone and 6 months with deflazacort prior to chart review. Thirty patients had BMD with a mean age of 20.1 years at switch and an average treatment duration of 5.26 years (SD, 5.0) with prednisone and 6 months with deflazacort prior to chart review.

The average age of symptom onset was 4.1 years in patients with DMD and 8.3 years in patients with BMD. Patients with DMD more commonly experienced loss of ambulation (24%) at a mean age of 9 years compared to those with BMD (17%; 18 years).

Marden and colleagues found that the primary reason for switch was “desire to slow disease progression” in 83% of patients with DMD and 79% of patients with BMD, followed by “tolerability issues” in 67% of patients with DMD and 47% of patients with BMD. Switching was reported by 95% of patients with DMD and 90% of patients with BMD as “very” or “somewhat” effective at addressing these reasons.

Overall, during the average 6-month follow-up after switching, in patients in which Clinical Global Impression (CGI) scores were available, most disease progression improved or stabilized during steroid treatment, with a shift toward improvement after switching.

Commonly recorded adverse events (AEs) during prednisone and deflazacort treatment included weight gain, Cushingoid appearance, increased appetite, central obesity, and fluid retention, although the occurrence of AEs was lower during the deflazacort period for DMD patients. Patterns were similar for BMD patients.

“Future real-world studies with longer follow-up times on deflazacort are needed to comprehensively characterize the impact of switching from prednisone to deflazacort on dystrophinopathy patients,” Marden and colleagues concluded.

Deflazacort for Treatment of DMD 

Deflazacort was approved for the treatment of DMD in patients 5 years of age and older in February 2017. This approval was later extended to include patients between 2 and 5 years of age.^3,4 

The original approval was based on data from a phase 3, randomized, double-blind, placebo-controlled study of 196 patients with DMD aged 5 to 15 over a 52-week period that compared treatment with deflazacort with prednisone and placebo.

During an initial 12-week treatment period, muscle strength was significantly greater in the deflazacort group versus placebo. This treatment effect was continuously observed through week 52. Measures of motor function also favored deflazacort versus placebo.

"We're encouraged by the clinical benefit exhibited by patients taking EMFLAZA in this real-world analysis," said Stuart W. Peltz, PhD, chief executive officer, PTC Therapeutics, on the results of the real-world study. "This data supports the results that we saw in patients on corticosteroids in the placebo arms of multiple Duchenne clinical trials and what we have heard from the Duchenne community. We are committed to providing access to clinically differentiated treatments for patients with high unmet need."

For more coverage of MDA 2021, click here.

REFERENCES

1. PTC presents results from a real-world study of steroid switching in the treatment of patients with dystrophinopathies. News release. PTC Therapeutics. Published online March 15, 2021. https://ir.ptcbio.com/news-releases/news-release-details/ptc-presents-results-real-world-study-steroid-switching
2. Marden J, Santos C, Pfister B, et al. Steroid switching in the treatment of dystrophinopathies in the US: A nationwide chart review of patient characteristics and clinical outcomes. Presented at MDA Clinical and Scientific Conference 2021; March 15–18.
3. FDA approves drug to treat Duchenne muscular dystrophy. News release. US Food and Drug Administration. Published online February 9, 2017. www.fda.gov/news-events/press-announcements/fda-approves-drug-treat-duchenne-muscular-dystrophy.
4. PTC Therapeutics receives FDA approval for the expansion of the Emflaza® (deflazacort) labeling to include patients 2-5 years of age. News release. PTC Therapeutics. Published online June 7, 2019. www.prnewswire.com/news-releases/ptc-therapeutics-receives-fda-approval-for-the-expansion-of-the-emflaza-deflazacort-labeling-to-include-patients-2-5-years-of-age-300863988.html.