FDA approves UCB Treatment for TK2d

Rare Daily Staff

The U.S. Food and Drug Administration has approved UCB’s Kygevvi, the first and only approved treatment for the ultra-rare mitochondrial disease thymidine kinase 2 deficiency.

Thymidine kinase 2 deficiency (TK2d) is a life-threatening genetic disease characterized by progressive and severe muscle weakness. It is often fatal, with those experiencing initial symptoms on or before age 12 facing a high risk of premature death, often occurring within three years after symptom onset.

Kygevvi is a combination of doxecitine and doxribtimine, both pyrimidine nucleosides, indicated for the treatment of TK2d in adults and pediatric patients whose symptom onset occurred on or before age 12. Administration of Kygevvi is intended to incorporate the pyrimidine nucleosides deoxycytidine and deoxythymidine into skeletal muscle mitochondrial DNA. This action restores mitochondrial DNA copy number in TK2d mutant mice.

In the United States, Kygevvi received Orphan Drug, Breakthrough, Priority Review, and Rare Pediatric Disease designations from the FDA. With the FDA approval, UCB was awarded a Rare Pediatric Disease Priority Review Voucher, which may be redeemed for priority review of a future marketing application.

A regulatory review of doxecitine and doxribtimine is currently underway by the European Medicines Agency.

The Kygevvi approval is supported by safety and efficacy data from one Phase 2 clinical study, two retrospective chart review studies, and an expanded-access program. These studies included a total of 82 unique patients treated with Kygevvi or pyrimidine nucleosides. All had symptom onset of TK2d at age 12 or younger.

Efficacy was assessed by comparing overall survival in pediatric and adult treated patients with an external control group of untreated patients matched by age at symptom onset. A total of 78 matched pairs were identified.

Results showed that survival time from treatment start improved, and treatment reduced the overall risk of death from treatment start by approximately 86 percent.

The most common adverse reactions are diarrhea, abdominal pain, vomiting, and increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

“It’s hard to overstate the importance of this FDA approval for those diagnosed with TK2d. This is an ultra-rare disease community in dire need of treatment options. For too long, caregivers and their families have had to endure the burden of this disease,” said Kristen Clifford, president and CEO of the United Mitochondrial Disease Foundation. “Having the first-ever FDA-approved therapy for TK2d in this patient population not only meets a critical medical need, it represents something greater — hope for the future.”