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Positive Phase 1/2 Clinical Trial Results of Genethon’s Gene Therapy for Crigler-Najjar Syndrome, a Rare Liver Disease, Published in The New England Journal of Medicine

Results represent the first clinical demonstration of the efficacy of gene therapy in a metabolic disease of the liver

PARIS–(BUSINESS WIRE)–Genethon, a pioneer and leader in gene therapy research and development for rare genetic diseases, announced today positive Phase 1/2 clinical trial results of its gene therapy, GNT-0003, for Crigler-Najjar syndrome were published in The New England Journal of Medicine. The data demonstrate the possibility of restoring expression of liver enzyme UGT1A1 by using gene therapy in cases of Crigler-Najjar syndrome.

Crigler-Najjar is characterized by hyperbilirubinemia and caused by a deficiency in the enzyme UGT1A1. If not treated quickly, the build-up of bilirubin can cause significant neurological damage and become fatal. The only current treatments are phototherapy of up to 12 hours per day or a liver transplant. GNT-0003 combines an AAV8 vector with a normal copy of gene UGT1A1 coding for the bilirubin metabolizing enzyme.

The Phase 1/2 trial results published in an article titled, “Gene Therapy in Patients with the Crigler-Najjar Syndrome,” showed GNT-0003 lowered bilirubin levels below the toxic threshold with a single intravenous injection. The data also confirmed the safety and tolerance of the treatment for all patients in the study. Three patients, treated with the highest dose, have been able to stop using phototherapy for the last 18 months or more. This is the first proof of the efficacy of a gene therapy in a metabolic disease of the liver.

A pivotal study of GNT-0003 is underway to confirm the Phase 1/2 results in a larger number of patients including children aged 10 years and older.

“If the results of the pivotal part confirm the efficacy of our gene therapy for Crigler-Najjar syndrome, we will be able to move on to a product license application, making the treatment available to patients and providing them with significantly improved quality of life,” said Genethon CEO Frederic Revah.

The Crigler-Najjar clinical trial is being conducted with the European consortium CureCN. It started in 2017 in four centers in Europe: France (Prof. Phillipe Labrune – Hôpital Béclère in Clamart); Italy (Prof. Lorenzo d’Antiga – Azienda Ospedaliera Papa Giovanni XXIII in Bergamo along with Prof. Brunetti-Pierri – Hôpital Federico II); and Netherlands (Prof. Ulrich Beuers – Academic Medical Center in Amsterdam).

Professor Labrune said, “As the PI of this trial, I consider these first results to be exciting, encouraging, and even moving. We are confident the results of the pivotal part will confirm the efficacy of this gene therapy. Providing a treatment for Crigler-Najjar disease could be the beginning of new adventures for other hepatic metabolic diseases.”

Professor D’Antiga added, “After haemophilia, Crigler-Najjar syndrome is the next liver disease treated by gene therapy. In this trial we managed to restore the synthesis of a non-secreted protein whose deficiency causes severe jaundice in affected patients.”

Professor Beuers observed, “We are most grateful to our participating patients and the whole group of contributors who made these first promising clinical results possible. Piter Bosma in our group started experimental work on this topic 20 years ago. This proves that creativity, dedication and persistence of the whole team may pay off for our patients’ well-being.”

About Genethon

As a pioneer in the discovery and development of gene therapies for rare diseases, Genethon is a non-profit laboratory that was established by AFM-Telethon. A first gene therapy for spinal muscular atrophy to which Genethon contributed has obtained a product license. With more than 200 scientists and professional staff, Genethon is pursuing its aim to develop therapies which change the lives of patients suffering from rare genetic diseases. Thirteen products developed by Genethon are in clinical trial for diseases of the liver, blood, immune system, muscles and eyes. Seven other products could enter clinical trials over the next five years. More information at


US Contact:

Charles Craig

Opus Biotech Communications

EU Contacts:

Stéphanie Bardon, Marion Delbouis

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