New data presented at ACMG 2026 show that Otsuka’s investigational therapy repinatrabit reduced blood phenylalanine levels by 67% in adolescents with phenylketonuria in an open-label extension study, while a global Phase 3 trial in adults is ongoing.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
Otsuka Pharmaceuticals reported new data showing that the investigational therapy repinatrabit (JNT-517) produced substantial reductions in blood phenylalanine (Phe) levels in adolescents with phenylketonuria (PKU). The findings were presented at the 2026 American College of Medical Genetics and Genomics (ACMG) meeting.
In the open-label extension of a Phase 2 adolescent study (NCT06637514), patients receiving repinatrabit 75 mg twice daily achieved a mean 67% reduction in blood Phe levels from baseline at the first evaluable time point (Day 56 / OLE Month 1). All participants in the cohort showed a clinical response, including adolescents previously treated with sapropterin as well as one sapropterin-naïve patient.
Repinatrabit was well tolerated, with a safety profile consistent with earlier adult Phase 2 findings. No new treatment-related adverse events or serious adverse events were reported. The adolescent study is ongoing, with additional participants advancing to evaluation of the 150 mg dose.
“These data mark an important milestone in our efforts to advance the understanding and treatment of PKU,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka, noting that maintaining control of blood Phe levels remains a major challenge for adolescents with the disorder.
Separately, Otsuka is conducting the global Phase 3 PheORD trial (NCT06971731) in adults with PKU. The randomized, double-blind, placebo-controlled study will enroll about 120 patients, who will receive repinatrabit 75 mg, 150 mg twice daily, or placebo for six weeks. The primary endpoint will evaluate mean reductions in blood Phe levels at Weeks 2, 4, and 6, followed by longer-term treatment and follow-up through 52 weeks. Primary endpoint results are expected in late 2026.
Repinatrabit is a selective small-molecule inhibitor of the phenylalanine transporter SLC6A19, designed to block kidney reabsorption of phenylalanine and lower circulating Phe levels. The therapy has received FDA orphan drug and rare pediatric disease designations for the treatment of PKU.
Phenylketonuria (PKU) is a genetic metabolic disorder caused by pathogenic variants in the phenylalanine hydroxylase (PAH) gene, which prevents the body from properly metabolizing phenylalanine. The resulting buildup of Phe can lead to toxic accumulation in the body, including the brain, potentially causing neurological and cognitive complications if not controlled.
Reference
Otsuka Unveils New Repinatrabit Open-Label Extension Data in Phenylketonuria (PKU) Signaling Efficacy in Adolescents at the 2026 American College of Medical Genetics and Genomics (ACMG) Meeting, 13 March 2026, Otsuka Unveils New Repinatrabit Open-Label Extension Data in Phenylketonuria (PKU) Signaling Efficacy in Adolescents at the 2026 American College of Medical Genetics and Genomics (ACMG) Meeting｜March 13, 2026｜News Releases | Otsuka Pharmaceutical Co., Ltd.
A Phase 2 Study of JNT-517 in Adolescent Participants with Phenylketonuria, ClinicalTrials.gov ID NCT06637514, https://clinicaltrials.gov/study/NCT06637514
About the Writer
Chikkula Pavan Kumar, PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.