Phase 1/2 Trial Tested Use of Losartan Repurposed for RDEB
In RDEB, mutations in the COL7A1 gene lead to a faulty or missing C7 protein, crucial for connecting skin layers. This results in symptoms like blisters and scar tissue formation, affecting not just the skin but also other body parts such as the digestive tract, kidneys, mouth, and eyes. Chronic itch and pain associated with RDEB significantly limit patient quality of life.
Losartan, a medication used to treat high blood pressure, was repurposed for this trial based on previous studies showing its potential to reduce inflammation and scar tissue formation in RDEB mouse models.
The REFLECT trial, an open-label Phase 1/2 clinical trial, evaluated losartan in 29 children aged 2-14 with moderate or severe RDEB. Over 10 months, children received increasing doses of oral losartan, followed by a period of dose reduction and a three-month follow-up without the drug.
Greatest Benefits Seen Among Patients with Severe Disease
At week 40, nearly half of the patients (46.4%) saw a clinically meaningful reduction in disease activity, with the overall mean drop being 7.36 EBDASI activity points. Greater reductions were observed in patients with severe RDEB compared to those with moderate RDEB.
Losartan treatment led to improvements in skin involvement, with fewer skin lesions and less redness. Benefits were also seen in patient-reported pain, itch, and quality of life, alongside significantly decreased levels of TNF, a protein marker for inflammation.
Losartan was well tolerated, with no treatment-related severe complications or serious safety concerns, including effects on blood pressure. The researchers concluded that losartan may reduce disease burden in children with RDEB, emphasizing the need for further research with larger sample sizes and longer durations to establish long-term efficacy and safety.
