The del-zota phase 3 SAFARI44 clinical trial for Duchenne muscular dystrophy represents a major step toward developing targeted treatments for patients with exon-44–amenable genetic mutations in Duchenne Muscular Dystrophy. Learn More: Mutations and Deletions Amenable to Exon 44 Skipping Therapies
Presented at the Muscular Dystrophy Association Clinical & Scientific Conference, the SAFARI44 study evaluates the safety and effectiveness of del-zota, an investigational antibody-oligonucleotide conjugate (AOC) therapy developed by Avidity Biosciences.
The phase 3 clinical trial builds on encouraging early-stage data showing that del-zota may significantly improve dystrophin production and muscle function in patients with DMD caused by exon 44 mutations.
Table of Contents
What is SAFARI44 Phase 3 Clinical Trial
- Approximately 70 ambulatory patients aged 2 Years and older will participate.
- Participants will receive intravenous dosing every six weeks for 54 weeks.
- The clinical trial includes:
- Randomized double-blind treatment phase (54 weeks)
- Open-label extension (54 weeks)
- Safety follow-up (6 weeks)
- Participants will receive del-zota 5 mg/kg PMO (28 mg/kg total AOC weight) or placebo in a 1:1 randomization.
- A total of nine infusions will be administered during the blinded treatment period.
This design aims to determine whether del-zota can significantly improve muscle function and dystrophin production, key therapeutic targets for Duchenne muscular dystrophy.
Primary and Secondary Endpoints
The primary endpoint in the del-zota phase 3 SAFARI44 clinical trial is:
Change in time-to-rise velocity: a widely used functional measure reflecting lower-limb muscle strength.
Secondary outcome measures include:
- Creatine kinase (CK) levels
- 4-stair climb velocity
- 10-meter walk/run test
- SV95C stride velocity
- North Star Ambulatory Assessment (NSAA)
These metrics are commonly used in DMD clinical trials to evaluate disease progression and functional improvement. Learn More: Biomarkers in DMD
Mechanism of Del-Zota Therapy
Del-zota is an antibody-oligonucleotide conjugate (AOC) designed to deliver phosphorodiamidate morpholino oligomers (PMOs) directly to muscle tissue.
The therapy aims to:
- Skip exon 44 in the dystrophin gene
- Restore the reading frame of dystrophin mRNA
- Enable production of a shorter but functional dystrophin protein
This strategy may help stabilize muscle fibers and slow disease progression in patients whose mutations are amenable to exon-skipping therapies.
Earlier Clinical Data: EXPLORE44 Clinical Trial
The EXPLORE44 study builds on results from the EXPLORE44 phase 1/2 clinical trial, which included 26 participants with exon-44–amenable Duchenne muscular dystrophy.
Key Findings from EXPLORE44
Clinical data demonstrated:
- ~200 nM PMO concentrations in skeletal muscle
- ~25% of normal dystrophin levels
- 37% increase in exon-44 skipping
- >80% reduction in creatine kinase
Functional outcomes also showed encouraging results when compared with natural-history cohorts. Read More: Del-zota (EXPLORE44) Provides Nearly 30% Normal Dystrophin Production
Open-Label Extension (OLE) Results
Participants continuing treatment in the open-label extension experienced measurable functional benefits over 12–24 months.
Observed outcomes included:
- 4-stair climb test
- Improvement of 2.1 seconds
- Natural-history cohort declined by 2.7 seconds
- 10-meter walk/run
- 0.7-second improvement vs 1.5-second decline in untreated cohorts
- Time-to-rise from floor
- 3.2-second improvement vs 1.6-second decline
Additional findings included:
- Stable NSAA scores in treated patients
- 1.5-point improvement in Performance of Upper Limb (PUL) scores
These results suggest that del-zota may slow or stabilize functional decline, a major goal in Duchenne muscular dystrophy therapy.
Safety and Tolerability
Across early clinical studies, del-zota demonstrated a favorable safety profile:
- Most adverse events were mild to moderate
- No unexpected safety signals were reported
- Significant reductions in creatine kinase levels were observed
These findings support continued investigation in the phase 3 SAFARI44 clinical trial.
Why the SAFARI44 Clinical Trial Matters
The del-zota phase 3 SAFARI44 clinical trial for Duchenne muscular dystrophy could provide pivotal evidence supporting a new precision therapy for exon-44–amenable patients. Learn More: Upcoming Exon 44 Skipping Therapies for the Treatment of Duchenne
If successful, del-zota may:
- Increase dystrophin production
- Improve muscle function
- Delay disease progression
- Expand treatment options for the DMD community
In which countries will the Del-Zota Phase 3 SAFARI44 Clinical Trials begin?
The Phase 3 SAFARI44 clinical trial of del-zota is designed as a global clinical study, meaning recruitment will take place across multiple regions rather than a single country. The study is expected to enroll participants in several countries across Europe, Asia and other regions. Avidity Biosciences is expected to announce the countries where SAFARI44 will take place.
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