Phase 2a study of readthrough therapy in nonsense mutation Alport syndrome.

Daily subcutaneous exaluren (0.75 mg/kg) for 8 weeks in three adolescents with autosomal recessive Alport syndrome with COL4A4 nonsense mutations increased collagen α3(IV), α4(IV), and α5(IV) abundance.

• Why it matters: Nonsense mutation Alport syndrome has a particularly poor prognosis and no approved therapies, creating an unmet need for treatments that can restore full-length collagen IV production.
• What they did: In a proof-of-mechanism phase 2a study, three patients aged 12–18 received daily exaluren for 8 weeks, with safety assessed and kidney biopsies compared before versus after treatment.
• The result: No new safety signals emerged, and biopsy findings showed readthrough-linked collagen IV changes and partially improved podocyte morphology in all participants, supporting further trials despite inconsistent proteinuria and persistent hematuria.

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