European Commission approves Kygevvi (doxecitine and doxribtimine) as first and only treatment for thymidine kinase 2 deficiency (TK2d) – UCB
UCB announced that the European Commission (EC) has granted marketing authorization under exceptional circumstances for Kygevvi (doxecitine and doxribtimine) for the treatment of paediatric and adult patients with genetically confirmed thymidine kinase 2 deficiency (TK2d) with an age of symptom onset on or before 12 years. It is the first and only approved treatment for TK2d.
“The European Commission’s approval of Kygevvi marks a historic milestone for the TK2d community. For the first time, people across Europe living with this ultra-rare, life-threatening mitochondrial disease have access to an approved treatment beyond supportive care,” said Donatello Crocetta, Chief Medical Officer at UCB. “Kygevvi is designed to support mitochondrial DNA maintenance in skeletal muscle, addressing a key biological driver of TK2d. We are deeply grateful to the patients, families, advocates, investigators, and clinical trial teams whose partnership, trust, and resilience made this achievement possible.”
“TK2d has a profound impact on people living with the condition and their families and, until now, they have faced a heavy burden of unmet treatment need with incredible resilience,” said Caterina Garone, Associate Professor of Medical Genetics, University of Bologna, Italy. “The TK2d community has waited a long time for this moment which brings them new hope and marks an important step forward in how clinicians can manage this devastating disease.”
Clinical efficacy
Supporting data for EC approval came from pooled data from two studies of treatment with Kygevvi (doxecitine and doxribtimine) in patients with genetically confirmed TK2d with age of symptom onset ≤12 years. These studies investigated the impact of treatment on functional outcomes (i.e. motor milestones, ventilatory support, feeding support) as well as survival. In the studies, Kygevvi was well tolerated with the most commonly reported adverse reactions of diarrhea (86%), vomiting (28%), abdominal pain (including abdominal pain upper) (26%).
Developmental motor milestone ability: A decrease in the loss of motor milestones was observed following treatment initiation with Kygevvi; 26/31 (84%) patients regained one or more motor milestones (e.g. sitting upright unassisted, holding head upright unassisted).
Ventilatory support: Prior to treatment start, 18/39 (46%) participants initiated ventilatory support and no participants discontinued ventilatory support. After initiation of treatment, 5/21 (24%) participants started ventilatory support while 5/23 (22%) discontinued ventilatory support.
Feeding support: Prior to treatment start, 12/39 (31%) participants had a feeding tube. After initiation of treatment, 4/28 (14%) participants started feeding support, with 2 of these participants subsequently discontinuing feeding support after initiation of treatment.
Kygevvi was supported through EMA’s PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a potential to address patients’ unmet medical needs. Marketing authorization under exceptional circumstances may be granted to medicines where the applicant is unable to provide comprehensive data on efficacy and safety under normal conditions of use, because the condition to be treated is rare or because collection of full information is not possible or is unethical.
The EC approval follows the recent approval of Kygevvi by the FDA for the treatment of adults and pediatric patients living with thymidine kinase 2 deficiency (TK2d), with an age of symptom onset on or before 12 years.
