Kygevvi Becomes First FDA-Approved Treatment for Rare Mitochondrial Disorder TK2d

The FDA has approved Kygevvi (doxecitine and doxribtimine), the first treatment available for thymidine kinase 2 deficiency (TK2d), a rare genetic mitochondrial disorder that causes progressive muscle weakness and respiratory failure.

Developed by UCB, the therapy is approved for adults and children who developed symptoms before age 12.

This decision offers the first targeted treatment for a patient community that so far relied solely on supportive and palliative care.

UCB expects to make Kygevvi available in the US in early 2026.

The drug has also received Orphan Drug, Breakthrough Therapy, Priority Review and Rare Pediatric Disease designations from the FDA.

What Is T2kD?

TK2d stems from mutations in the TK2 gene that prevent cells from maintaining healthy mitochondrial DNA.

Because mitochondria are present in nearly every cell, the disease can affect multiple systems, particularly skeletal muscles.

Most patients experience early-onset symptoms such as severe muscle weakness, drooping eyelids, difficulty walking and swallowing challenges that can progress to respiratory failure.

Over time, many lose the ability to walk, eat or breathe independently. Symptoms may also appear later in life but tend to progress more slowly in those cases.

What Is Kygevvi and Its Phase II Performance

Kygevvi combines two pyrimidine nucleosides — doxecitine and doxribtimine — which work together to replenish mitochondrial DNA in skeletal muscle. In simpler terms, the therapy helps restore the cell’s energy-producing machinery that becomes impaired in TK2d.

It is supplied as an oral powder solution.

The FDA based its decision on data from one Phase II clinical trial, two retrospective chart reviews and an expanded access program that collectively included 82 patients with symptom onset before age 12.

Among 78 matched pairs of treated and untreated patients, only 4% of those receiving the drug died during the study period, compared with 36% in the control group. The mean survival time at 10 years was 9.6 years for those treated with Kygevvi versus 5.7 years for untreated patients.

Overall, treatment with Kygevvi reduced the risk of death by approximately 86%, a striking improvement given the disease’s historically poor prognosis. The median treatment duration was four years, and most participants began therapy at around 1.5 years of age.

There were nearly 1,200 known TK2d cases across the US, Europe and Japan in 2024, with numbers expected to rise as access to genetic diagnostics improves.

T2KD disease management currently focuses on symptom relief through a multidisciplinary care model. Patients often require respiratory support as well as physical and occupational therapy to maintain mobility and quality of life.

Some patients also use nutritional supplements, sometimes referred to as “mito-cocktails,” to manage energy loss.

Kygevvi introduces a new approach by directly targeting the cellular deficit that defines TK2d.

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What’s Next?

A regulatory review is currently underway in Europe, and additional submissions are planned in other regions.

For families affected by TK2d, Kygevvi represents a meaningful shift in care. Ongoing post-approval studies will help clarify how restoring mitochondrial DNA may change long-term outcomes for individuals living with severe inherited energy disorders.

Broadly, mitochondrial diseases collectively affect an estimated 1 in 5,000 people, and about 1,000 to 4,000 children in the US are born each year with a mitochondrial disease.

Beyond TK2d, two mitochondrial disease candidates have advanced to Phase III development. Sonlicromanol is an investigational oral small-molecule redox modulator being developed by Khondrion for the treatment of primary mitochondrial diseases. The European Commission has granted Orphan Drug designation for inherited oxidative phosphorylation (OXPHOS) defects.

GenSight Biologics’ GS010/LUMEVOQ (lenadogene nolparvovec) is an investigational AAV2-based gene therapy that delivers a functional ND4 gene through intravitreal injection for the rare blinding disease Leber hereditary optic neuropathy (LHON). In October 2025, the FDA authorized individual patient expanded access for treatment at the University of Pittsburgh.