Roche halts development of satralizumab for DMD bone health
Feasibility of achieving regulatory requirements among concerns behind decision
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Roche has decided to stop developing satralizumab for bone health in Duchenne muscular dystrophy (DMD), the company announced in a community letter.
Patients already enrolled in the SHIELD DMD Phase 2 trial (NCT06450639) may continue on the study until the six-month bone mineral density collection, expected in the second half of the year. Those currently in screening who are deemed eligible may still join the trial until that same time point.
“While we will not be advancing satralizumab in bone health, we are committed to sharing the interim study data with the research and family communities to help advance the understanding of Duchenne,” the company stated. “We are profoundly grateful to all patients, families, healthcare providers, study sites and research partners who contributed to this research.”
According to the company, the decision concerns whether it was feasible to achieve regulatory requirements and meet timelines for patient recruitment and trial completion. Based on these issues, the company stated it no longer sees a viable path forward to develop satralizumab in DMD.
“Without a realistic path to approval, continuing the study for longer would place an undue burden on trial families, sites and the broader community,” Roche stated. The company noted that the decision was not related to unexpected safety issues or new efficacy data.
Satralizumab blocks key protein receptor
DMD is caused by mutations in the DMD gene that result in a complete lack of functional dystrophin, a protein that helps protect muscles from damage during movement. The loss of dystrophin leads to progressive muscle weakness and wasting.
Chronic inflammation and treatment with corticosteroids to reduce inflammation may reduce bone mineral density, the amount of calcium and other minerals in the bones. More minerals mean denser and stronger bones that are less likely to break.
Preclinical findings in DMD mouse models have suggested that blocking interleukin (IL)-6 signaling may be an effective way to treat bone loss in DMD.
Satralizumab is an antibody-based therapy that blocks the IL-6 protein receptor. IL-6 is a molecule involved in muscle repair and regeneration. However, IL-6 levels are high in people with DMD, contributing to inflammatory responses and repeated cycles of muscle degeneration.
The Phase 2 trial, running in the U.S, Denmark, Italy, Poland, Spain, and Ukraine, aimed to enroll 50 boys with DMD, ages 8 to 17 years, who were taking corticosteroids. Participants received satralizumab via subcutaneous (under the skin) injection on day one, in weeks two and four (loading doses), and then once every four weeks as maintenance doses.
There are times when our assessment results in difficult decisions that affect an ongoing clinical study. These decisions are never taken lightly and are made with thoughtful consideration, guided by a systematic evaluative framework. We recognise that these decisions are never easy because they impact people.
The trial’s main goal was to assess the treatment’s effect on bone mineral density after one year. Secondary goals included evaluating bone density at other time points (six months and two years), changes in bone metabolism biomarkers, and the occurrence of new bone fractures.
“We are communicating with health authorities and investigators about this closure, transition plans, and support for sites and participants,” Roche stated. “SHIELD DMD has less than 30 participants enrolled and our priority is supporting transition for them and those in the screening process.”
The news was met with disappointment at Parent Project Muscular Dystrophy.
“Bone health remains a critical component of comprehensive Duchenne care,” the organization said in a press release. “We will continue to work with partners across research and care to address unmet needs and ensure families are informed and supported as the field moves forward.”
Roche said a lot of thought went into the decision.
“There are times when our assessment results in difficult decisions that affect an ongoing clinical study. These decisions are never taken lightly and are made with thoughtful consideration, guided by a systematic evaluative framework,” Roche added. “We recognise that these decisions are never easy because they impact people.”
Satralizumab is approved under the brand name Enspryng for certain patients with neuromyelitis optica spectrum disorder, an autoimmune disease caused by inflammation and damage to the nervous system.
