Functional Outcomes in Patients with Thymidine Kinase 2 Deficiency Aged ≤12 Years at Symptom Onset Who Received Pyrimidine Nucleos(t)ide Therapy

Topic:

Clinical Trials

Poster Number: P255

Author(s):

Caterina Garone, MD, PhD, University of Bologna and IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy, Michio Hirano, MD, Columbia University Irving Medical Center, New York, NY, USA, Richard Haas, MB, BChir, MRCP, University of California and Rady Children's Hospital, San Diego, CA, USA, Carmen Paradas, MD, Hospital Universitario Virgen del Rocío, Seville, Spain; CIBERNED, ISCIII, Madrid, Spain, Fernando Scaglia, MD, Baylor College of Medicine and Texas Children’s Hospital, TX, USA; CUHK-BCM Joint Centre, Hong Kong, Cynthia Beller, UCB, Morrisville, NC, USA, Carl Chiang, PhD, UCB, Morrisville, NC, USA, Anny-Odile Colson, PhD, UCB, Colombes, France, Susan VanMeter, MD, UCB, Cristina Domínguez-González, MD, PhD, Hospital Universitario 12 de Octubre Research Institute and CIBERER, ISCIII, Madrid, Spain

Thymidine kinase 2 deficiency (TK2d) is an ultra-rare, autosomal recessive, mitochondrial disease associated with progressive, life-threatening proximal myopathy. Early age at symptom onset is associated with rapid disease progression. No treatments are approved; however, pyrimidine nucleoside therapy with doxecitine and doxribtimine is in development. We assessed functional outcomes and safety in patients with an age of TK2d symptom onset ≤12 years who received pyrimidine nucleos(t)ides.

Patients treated with pyrimidine nucleos(t)ides were pooled from retrospective (NCT03701568, NCT05017818) and prospective (NCT03845712) sources and a company-supported expanded access program (EAP; functional outcome data not collected). Developmental motor milestone profiles and use of ventilatory and feeding support were compared pre- and post-treatment.

Overall, 82 patients with an age of TK2d symptom onset ≤12 years were treated with pyrimidine nucleos(t)ides (median [Q1, Q3] treatment duration: 54.8 [15.2, 78.4] months). Pre-treatment, 83.7% of patients (41/49) lost ≥1 motor milestone and 40.8% (20/49) lost ≥4 (missing/not-at-risk=33); 4.9% of patients (2/41) regained ≥1 previously lost motor milestone (missing/not-at-risk=41). Post-treatment, 21.7% of patients (10/46) lost ≥1 motor milestone and 2.2% (1/46) lost ≥4 (missing/not-at-risk=36); 75.0% (30/40) regained ≥1 previously lost motor milestone, and 22.5% (9/40) regained ≥4 (missing/not-at-risk=42). Of 31 patients (37.8%) using ventilatory support at treatment initiation (missing=29), 16.1% (5/31) reduced hours of use and 16.1% (5/31) discontinued support post-treatment. Of 19 patients (23.2%) using feeding support at treatment initiation (missing=30), few (2/19 [10.5%]) discontinued support post-treatment. In the safety population (n=50; EAP not included), two patients (4.0%) experienced TEAEs leading to treatment discontinuation; among those with available data, the most common TEAE was diarrhea (33/39 [84.6%]).

In patients with an age of TK2d symptom onset ≤12 years, pyrimidine nucleos(t)ide therapy is well tolerated and may improve functional outcomes, including retaining or regaining motor milestones and stabilizing ventilatory and feeding support use.

Studies funded by UCB.