UCB has received European Commission approval for Kygevvi, the first and only authorised treatment for thymidine kinase 2 deficiency, an ultra-rare and life-threatening mitochondrial condition marked by progressive muscle weakness.

The decision covers paediatric and adult patients with genetically confirmed TK2d whose symptoms began at or before age 12.

Announcing the approval, UCB said Kygevvi is a 2g doxecitine/2g doxribtimine powder for oral solution and represents the first therapy available in the European Union beyond supportive care. The company noted that TK2d places a significant burden on patients and families due to its severe and progressive nature.

Donatello Crocetta, Chief Medical Officer at UCB, said: “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.

“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.”

Caterina Garone, Associate Professor of Medical Genetics at the University of Bologna, said: “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.”

The approval is supported by pooled data from two studies in patients with symptom onset at or before age 12. The trials assessed motor milestones, ventilatory and feeding support and survival. According to the data, Kygevvi was well tolerated, with the most common adverse reactions being diarrhoea, vomiting and abdominal pain.

Across the studies, 26 of 31 patients regained one or more motor milestones after starting treatment. Changes in ventilatory and feeding support also suggested clinical benefit, with some patients discontinuing support after initiation of therapy.

Positive high-level results from the phase 3 OBERON and TITANIA trials indicate that tozorakimab achieved statistically significant and clinically meaningful reductions in the annualised rate of moderate-to-severe COPD exacerbations compared with placebo.

The findings applied both to the primary population of former smokers and to the overall population, which included former and current smokers, with patients spanning all blood eosinophil counts and all stages of lung function severity. According to the data, tozorakimab was generally well tolerated with a favourable safety profile.

Tozorakimab is described as a potential first-in-class monoclonal antibody targeting interleukin-33, uniquely inhibiting signalling of both the reduced and oxidised forms of IL-33. The approach aims to reduce inflammation and disrupt the cycle of mucus dysfunction that contributes to COPD worsening.

In both trials, patients continued to experience exacerbations despite inhaled standard of care and received either tozorakimab 300mg or placebo once every four weeks on top of their existing treatment.

COPD affects nearly 400 million people worldwide and remains the third leading cause of death globally. Even with inhaled standard of care, more than half of patients continue to experience exacerbations, increasing the risk of cardiopulmonary events and mortality.

Frank Sciurba, Professor of Pulmonary and Critical Care Medicine at the University of Pittsburgh and Chief Investigator of the LUNA programme, said: “These trial results suggest that targeting the IL-33 pathway with tozorakimab delivers meaningful clinical benefit in a trial representing a broad COPD population, independent of smoking status and eosinophilic levels.

“COPD has long been a difficult-to-treat disease with inherent heterogeneity and significant unmet need, with up to half of patients worldwide at risk of exacerbations, hospitalisations, cardiopulmonary events and death — underscoring the importance of these results for advancing COPD science.”