DELOS
(2015)Objective
To evaluate the efficacy of idebenone on respiratory function in DMD patients not using glucocorticoids
Study Summary
• Idebenone 900 mg/day significantly reduced the loss of peak expiratory flow vs placebo
• Consistent benefit across multiple respiratory measures including FVC and FEV1
• Consistent benefit across multiple respiratory measures including FVC and FEV1
Intervention
Idebenone 300 mg three times daily (900 mg/day) vs placebo
Inclusion Criteria
DMD patients aged 10-18 years not using concomitant glucocorticoids
Study Design
Arms: Idebenone 900 mg/day, Placebo
Patients per Arm: 31 idebenone, 33 placebo (ITT)
Outcome
• PEF %predicted: idebenone -2.57%p vs placebo -8.84%p, difference 6.27%p (95% CI 0.61-11.93, p=0.031)
• Significant benefits also seen in FVC and FEV1
• Well tolerated; diarrhea more common with idebenone (25% vs 12%) but transient
• Significant benefits also seen in FVC and FEV1
• Well tolerated; diarrhea more common with idebenone (25% vs 12%) but transient
Bottom Line
Idebenone 900 mg/day significantly reduced decline in peak expiratory flow and other respiratory measures over 52 weeks in non-steroid DMD patients.
Major Points
- Idebenone (synthetic CoQ10 analogue) slowed decline in respiratory function in DMD not on corticosteroids.
- Peak expiratory flow (PEF) % predicted: -2.57% (idebenone) vs -6.02% (placebo) at 52 weeks; P=0.031.
- FVC % predicted: also showed less decline with idebenone (P=0.055, borderline).
- 64 DMD patients (ages 10-18) NOT on glucocorticoids. 52-week, double-blind, placebo-controlled.
- Idebenone 900 mg/day (300mg TID). Santhera Pharmaceuticals.
- First positive respiratory outcome trial in glucocorticoid-naïve DMD.
- AEs: gastrointestinal (diarrhea, abdominal pain) most common. Generally well tolerated.
- Published Lancet 2015 (Buyse et al.). European multicenter.
- EMA refused approval citing limited population (non-steroid users are minority of DMD).
- Demonstrated respiratory function as a viable DMD trial endpoint.
Study Design
- Study Type
- Phase 3 randomized controlled trial
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 64
- Follow-up
- 52 weeks
- Countries
- Belgium, Germany, Netherlands, Switzerland, France, Sweden, Austria, Italy, Spain, USA
Primary Outcome
Definition: Change in peak expiratory flow as %predicted from baseline to week 52
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| -8.84%p (p<0.0001) | -2.57%p (p=0.215) | - (Difference: 6.27%p (95% CI 0.61-11.93)) | 0.031 (ITT); 0.044 (mITT) |
Limitations & Criticisms
- Small sample size (64 patients; mITT only 57)
- Only studied patients NOT using glucocorticoids, limiting generalizability to the majority of DMD patients who are on steroids
- Respiratory endpoints only -- no motor function endpoints assessed
- 52-week duration; long-term respiratory benefit unknown
- Manufacturer-funded (Santhera Pharmaceuticals)
Citation
Buyse GM et al. Lancet. 2015 May 2;385(9979):1748-1757. DOI: 10.1016/S0140-6736(15)60025-3. PMID: 25907158. NCT01027884