SHIELD-DMD to Evaluate Therapeutic Potential of IL-6 Receptor Satralizumab in Duchenne Muscular Dystrophy

Crystal Proud, MD

(Credit: Children’s Hospital of the King’s Daughters)

A new phase 2 clinical trial, dubbed SHIELD-DMD (NCT06450639), is evaluating satralizumab (Enspryng; Roche), a monoclonal antibody targeting the interleukin-6 receptor (IL-6R), for its potential to improve bone strength and muscle function in boys with Duchenne muscular dystrophy (DMD). SHIELD-DMD is the first trial in DMD to explore IL-6R inhibition as a strategy for improving bone health and muscle function, and if successful, could support a new therapeutic approach to managing skeletal complications associated with DMD and long-term corticosteroid use.

The design of the trial was recently presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 16-19 in Dallas, Texas, by lead author Crystal Proud, MD, director of neurology and neuromuscular medicine at the Children’s Hospital of the King’s Daughters.¹SHIELD-DMD is an open-label trial enrolling boys with DMD who are receiving daily corticosteroids. Participants are divided into 2 groups based on age and fracture history: Group 1 includes boys aged 8 to 16 years with prior low-trauma fractures, and Group 2 consists of fracture-naïve ambulatory boys aged 8 to 12 years. Initially, nonambulatory boys aged 12 years and older will be included in Group 1, pending interim safety and pharmacokinetics (PK) data.

Participants receive weight-based fixed doses of subcutaneous satralizumab at baseline, Week 2, Week 4, and then every 4 weeks for up to 2 years. The study’s primary end point is the change in lumbar spine bone mineral density (BMD) Z-score from baseline to Week 52 in fracture-naïve patients, with adjustments for bone size. Additional endpoints include changes in BMD Z-score and bone turnover markers across all patients, fracture incidence, and functional measures such as rise-from-the-floor velocity. Safety, PK, and immunogenicity will also be evaluated.

DMD is characterized by progressive muscle atrophy, chronic inflammation, and reduced bone mass, leading to increased fracture risk—an issue further exacerbated by long-term corticosteroid use. Elevated IL-6 levels have been linked to muscle atrophy, inflammation, and increased bone resorption in DMD, while IL-6R concentration correlates negatively with total body less head BMD Z-scores. Given its role in other inflammatory conditions, IL-6R inhibition may provide a novel approach to mitigating these issues in DMD.

READ MORE: Ifetroban Shows Promise in Slowing Cardiac Decline in Duchenne Muscular Dystrophy

In August 2020, the FDA approved satralizumab for use in adult patients with aquaporin-4-IgG-seropositive (AQP4 IgG+) neuromyelitis optica spectrum disorder (NMOSD) which is the third targeted treatment for this population and the first eligible for at-home administration.² The approval was based on robust data from the phase 3 SAkuraStar (NCT02073279) and SAkuraSky (NCT02028884) clinical trials, which combined included more than 170 patients who were randomly assigned to receive satralizumab 120 mg or placebo. In SAkuraSky, patients added treatment to baseline immunosuppressive therapy.

All patients received a loading dose of the study drug at baseline, week 2, and week 4, followed by 4-week treatment intervals. The primary end point in both studies was time to protocol-defined relapse. Notably, both studies included a population of patients who were AQP4-IgG antibody positive and negative to accurately reflect clinical practice.

In SAkuraStar, 30% of patients treated with satralizumab monotherapy experienced relapse compared with 50% of those who received placebo (HR 0.45; 95% CI, 0.23—0.89; P =.018).³ Among those who were AQP4-IgG antibody positive, a 74% reduction in relapse risk was observed. In the overall satralizumab-treated population, 76.1% and 72.1% were relapse-free at 48 and 96 weeks, respectively, compared with 61.9% and 51.2% with placebo. Data from the AQP4-IgG seropositive subgroup showed that 82.9% and 76.5% were relapse-free at 48 and 96 weeks compared with 55.4% and 41.1% with placebo, respectively.

In total, 92% (n = 58) of those in the satralizumab group experienced an adverse event compared with 75% (n = 24) of the placebo group. Serious AEs were similar between groups; only 1 event led to study drug discontinuation in the treatment group.

In SAkuraSky, the overall population saw a 62% reduction in the risk of relapse (HR 0.38, 95% CI, 0.16-0.88; P =.0184), while the group of AQP4-IgG seropositive patients experienced a 79% reduction in relapse risk (HR 0.21, 95% CI, 0.06-0.75; P =.0086).⁴ Results showed 88.9% and 77.6% of patients in the total population were relapse-free at 48 and 96 weeks, respectively, compared with 66% and 58.7% of patients in the placebo group. Among AQP4-IgG seropositive patients, 91.5% treated with satralizumab were relapse-free at 48 and 96 weeks compared with 59.9% and 53.3% of patients in the placebo group. The most common AEs observed were upper respiratory tract infection, nasopharyngitis, and headache.

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REFERENCES
1. Proud C, De Ford C, Guridi M, et al. Impact of satralizumab on bone strength and muscle function in Duchenne muscular dystrophy (DMD): design of the SHIELD-DMD study. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-19. Dallas, TX. Abstract P82
2. FDA approves Genentech’s Enspryng for neuromyelitis optica spectrum disorder. News release. Genentech. August 14, 2020. Accessed March 18, 2025. https://www.businesswire.com/news/home/20200814005501/en/ADDING-MULTIMEDIA%C2%A0FDA-Approves-Genentech%E2%80%99s-Enspryng-Neuromyelitis-Optica
3. Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomized, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402­-412. doi: 10.1016/S1474-4422(20)30078-8
5. Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019; 381:2114-2124. doi:10.1056/NEJMoa1901747