UCB's Kygevvi Marks First FDA Approval for Ultra-Rare Mitochondrial Disease

The U.S. Food and Drug Administration (FDA) has granted approval to UCB's Kygevvi, a groundbreaking therapy for thymidine kinase 2 deficiency (TK2d), an ultra-rare mitochondrial disorder. This milestone marks the first-ever approved treatment for TK2d, offering hope to patients with this life-threatening condition.

A Novel Approach to TK2 Deficiency

Kygevvi, a combination of doxecitine and doxribtimine, is delivered as an oral solution and is indicated for both adults and children with TK2d whose symptoms manifest by age 12. The therapy targets a condition affecting fewer than 2 in 1,000,000 people, caused by a mutation in the TK2 gene that impairs mitochondrial function.

TK2d typically presents as progressive muscle weakness and can lead to severe complications, including developmental delays, seizures, and respiratory failure. In its most severe forms, the disease can be fatal.

Clinical Efficacy and Safety Profile

The FDA's decision was based on comprehensive data from a Phase II clinical trial, two retrospective chart studies, and an expanded access program, encompassing a total of 82 TK2d patients. The results were striking, with Kygevvi demonstrating an 86% reduction in overall mortality risk compared to an untreated external control group of similar age.

Common adverse effects observed in clinical studies included gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Some patients also experienced elevated liver enzyme levels, warranting monitoring during treatment.

Impact on the Rare Disease Landscape

Kristen Clifford, president and CEO of the United Mitochondrial Disease Foundation, emphasized the significance of this approval, stating, "It's hard to overstate the importance of this FDA approval." She highlighted the critical need for treatment options among TK2d patients and their caregivers.

The approval of Kygevvi continues a positive trend in rare disease therapies. Recent FDA approvals in this space include Glaukos's Epioxa for keratoconus, Crinetics' Palsonify, and Stealth BioTherapeutics' Forzinity for Barth syndrome.

UCB plans to make Kygevvi available in the United States during the first quarter of 2026, potentially transforming the treatment landscape for patients with this ultra-rare mitochondrial disorder.