Drug Trials Snapshots KYGEVVI
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the KYGEVVI Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
KYGEVVI (doxecitine and doxribtimine)
(KY-JEH-vee)
UCB, Inc
Approval date: November 3, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
KYGEVVI is a combination of two medications, doxecitine and doxribtimine, both pyrimidine nucleosides, used for the treatment of thymidine kinase 2 deficiency (TK2d) in adults and children with a symptom onset on or before 12 years of age.
How is this drug used?
KYGEVVI is an oral powder that is mixed with water to be taken in three equal doses throughout the day with food. The dose is based on the patient’s weight.
Who participated in the clinical trials?
The FDA approved KYGEVVI based on the combined evidence from Trial 1 (NCT03845712), Study 1 (NCT03701568), Study 2 (NCT05017818), and an Expanded Access Program in 66 pediatric and 12 adult patients, with genetically confirmed TK2d with an age of symptom onset on or before 12 years of age. Patients were treated with KYGEVVI (or non-commercial doxecitine and doxribtimine). The studies were conducted at 39 centers among 20 countries including the United States, Argentina, Brazil, Chile, Costa Rica, France, Ghana, India, Ireland, Israel, Italy, Mexico, Romania, Russia, South Korea, Spain, Turkey, Ukraine, United Arab Emirates, and the United Kingdom. There were 17 patients from the United States and 61 patients were from outside the United States. The efficacy population (N=78) represents the indicated population of patients who had TK2d with a symptom onset on or before 12 years of age and the safety population (N=47) includes all study participants in Trial 1.
How were the trials designed?
Trial 1 is an ongoing trial in 47 adult and pediatric patients with TK2d. All patients received KYGEVVI; there was no comparison group in the study. The trial measured the amount of time that patients survived from the start of treatment.
Study 1 was a retrospective chart review study in 38 adult and pediatric patients with TK2d treated with doxecitine and doxribtimine. Vital status information was collected.
Study 2 was a retrospective chart review study in 61 adult and pediatric patients with TK2d; 43 untreated patients and 18 patients treated with doxecitine and doxribtimine. Vital status information was collected.
The Expanded Access Program included 43 patients with TK2d receiving KYGEVVI. Vital status information was collected.
The analyses focused on the patients with TK2d with a symptom onset on or before 12 years of age.
How were the trials designed?
In from Trial 1 (NCT03845712), Study 1 (NCT03701568), Study 2 (NCT05017818), and the Expanded Access Program, patients with TK2d received open-label treatment with an oral dose of KYGEVVI (or doxecitine and doxribtimine) of 800 mg/kg per day. The primary endpoint was survival in the 78 treated patients with TK2d symptom onset ≤12 years of age compared to an external control group of 78 untreated patients matched by age of symptom onset.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many female and male patients were enrolled in the studies used to evaluate the efficacy of KYGEVVI.
Figure 1. Baseline Demographics by Sex, Primary Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the studies used to evaluate the efficacy of KYGEVVI.
Figure 2. Baseline Demographics by Race, Primary Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the studies used to evaluate the efficacy of KYGEVVI.
Figure 3. Baseline Demographics by Age at Treatment Start, Primary Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the studies used to evaluate the efficacy of KYGEVVI.
Figure 4. Baseline Demographics by Ethnicity, Primary Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics in the Efficacy and Safety Populations
| Demographic Parameters | Efficacy Population N=78 |
Safety Population N=47 |
|---|---|---|
| Sex, n (%) | ||
| Female | 36 (46) | 20 (43) |
| Male | 42 (54) | 27 (57) |
| Age at treatment start, years | ||
| Mean (SD) | 8.1 (8.7) | 17.8 (18.7) |
| Median (min, max) | 4.2 (0.7, 35.5) | 9 (0, 75) |
| Age at treatment start, years, n (%) | ||
| ≤2 | 19 (24) | 6 (13) |
| >2 to <17 | 47 (60) | 25 (53) |
| ≥17 | 12 (15) | 16 (34) |
| Race, n (%) | ||
| American Indian or Alaska Native | 1 (1) | 1 (2) |
| Asian | 4 (5) | 1 (2) |
| Black or African American | 3 (4) | 1 (2) |
| Not reported | 1 (1) | 0 |
| Other | 2 (3) | 0 |
| Unknown | 3 (4) | 0 |
| White | 64 (82) | 44 (94) |
| Ethnicity, n (%) | ||
| Hispanic or Latino | 28 (36) | 14 (30) |
| Not Hispanic or Latino | 40 (51) | 33 (70) |
| Not reported | 6 (8) | 0 |
| Unknown | 4 (5) | 0 |
Source: Adapted from FDA Review
Abbreviations: SD, standard deviation
What are the benefits of this drug?
KYGEVVI reduced the overall risk of death in patients with TK2d with a symptom onset on or before 12 years of age compared to no treatment. There were three deaths (4%) in the patients receiving KYGEVVI compared with 28 deaths (36%) in the patients who did not receive treatment.
What are the benefits of this drug (results of trials used to assess efficacy)?
The primary efficacy endpoint was survival. Treatment reduced the overall risk of death from treatment start by approximately 86% (95% CI: 61%, 96%). Mean survival time at 10 years was 9.6 years for the group receiving KYGEVVI compared with 5.7 years in the control group.
Table 2 and Figure 5 summarize the clinical efficacy results of 78 patients with TK2d with a symptom onset on or before 12 years of age treated with KYGEVVI.
Table 2. Overall Survival in Patients With TK2d (Age of Symptom Onset ≤12 Years) Treated With KYGEVVI Versus Matched Untreated Patients (External Control)a
| Parameter | Treated Patients N=78 |
Matched Untreated Patients N=78 |
|---|---|---|
| Number of deaths (%)b | 3 (3.8%) | 28 (35.9%) |
| Restricted mean survival time, years (95% CI)b,c | ||
| At 4 years post treatment start | 3.8 (3.7, 4) | 2.6 (2.2, 3) |
| At 6 years post treatment start | 5.8 (5.5, 6) | 3.7 (3, 4.3) |
| At 10 years post treatment start | 9.6 (9.2, 10) | 5.7 (4.5, 6.9) |
| Hazard ratiod, for risk of death from treatment start (95%CI) | 0.14 (0.04, 0.39) | |
Source: KYGEVVI Prescribing Information
a Treated patients were originally from Trial 1 (N=9), Study 1 (N=27), Study 2 (N=11), and the expanded access program (N=31). Untreated patients were from published literature (N=57) and Study 2 (N=21).
b An additional censoring step for untreated subjects was performed for each matched pair where the untreated subject died and had a longer follow-up time than the matched treated subject who was censored. The follow-up time of the untreated subject was then censored at the follow-up time of the treated subject.
c Based on the area under the survival curves up to 4-, 6-, 10-years post treatment start.
d Estimates based on Cox Proportional Hazard Model with Firth correction that includes matched pair as a strata, age of symptom onset as a continuous covariate, and treatment (treated or untreated) as a time independent variable.
Abbreviations: CI, confidence interval; TK2d, thymidine kinase 2 deficiency
Figure 5. Kaplan-Meier Survival Curves for Time to Death From Treatment Start in Patients With TK2d Treated With KYGEVVI and Matched Untreated Patients (External Control)a,b
Source: KYGEVVI Prescribing Information
a Treated patients were from Trial 1, Study 1, Study 2, and the expanded access program. Untreated patients were from published literature and Study 2.
b Kaplan-Meier Curves with 95% confidence intervals using log-log transformation and with treatment group as strata variable; Age of TK2d Symptom Onset ≤12 years. An additional censoring step for untreated subjects was performed for each matched pair where the untreated subject died and had a longer follow-up time than the matched treated subject who was censored. The follow-up time of the untreated subject was then censored at the follow-up time of the treated subject.
Abbreviations: TK2d, thymidine kinase 2 deficiency
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: KYGEVVI worked similarly in males and females.
- Race: The number of patients of races other than White was small in the treated group. In addition, race was not available for the majority (68%) of the untreated subjects. Therefore, differences in how KYGEVVI worked among patient of different races could not be determined.
- Age: KYGEVVI worked similarly within pediatric patient age groups. The number of adult patients was small; therefore, differences between how the drug worked in pediatric and adult patients could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3 summarizes the results of the efficacy analysis by sex and age at treatment start in patients with TK2d receiving KYGEVVI. These results showed a survival benefit of treatment with KYGEVVI in all subgroups, except in the adult (≥17 years) subgroup where the number of subjects was too small to support reliable interpretation.
Table 3. Number of Deaths and Hazard Ratio by Sex and Age at Treatment Start, Primary Efficacy Population
| Subgroup | Number of Deaths (%) | Hazard Ratio (95% CI) | |
|---|---|---|---|
| Treated | Untreated | ||
| Sex1 | |||
| Female (n=20) | 1 (5.0) | 5 (25.0) | 0.106 (0.000, 0.998) |
| Male (n=27) | 1 (3.7) | 11 (40.7) | 0.153 (0.015, 0.678) |
| Age at treatment start, years | |||
| ≥2 (n=19) | 2 (10.5) | 15 (78.9) | 0.133 (0.007, 0.594) |
| <2 to <17 (n=47) | 0 (0.0) | 12 (25.5) | 0.070 (0.000, 0.380) |
| ≥17 (n=12) | 1 (8.3) | 1 (8.3) | 2.086 (NA, NA) |
Source: Adapted from FDA Review
1 To be included in the sex subgroups, both treated and untreated subjects within a matched pair should have the same sex.
Abbreviations: CI, confidence interval; NA, not applicable
What are the possible side effects?
KYGEVVI may cause serious side effects including diarrhea, vomiting, and increased liver enzymes levels in your blood.
The most common side effects of KYGEVVI include diarrhea, vomiting, stomach area (abdominal) pain, and increased liver enzymes levels.
What are the possible side effects (results of trials used to assess safety)?
Table 4 summarizes side effects reported by greater than 5% of patients with TK2d receiving KYGEVVI.
Table 4. Adverse Reactions That Occurred in ≥5% Adult and Pediatric Patients With TK2d Treated With KYGEVVI or Pyrimidine Nucleosides, Trial 1
| Adverse Reaction | Treated Patients N=47 n (%) |
|---|---|
| Diarrhea | 34 (72) |
| Abdominal pain (including abdominal pain upper) | 11 (23) |
| Vomiting | 10 (21) |
| Alanine aminotransferase increased (ALT) | 10 (21) |
| (AST) | 8 (17) |
Source: KYGEVVI Prescribing Information
Abbreviations: TK2d, thymidine kinase 2 deficiency
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The number of patients of races other than White was small; therefore, differences in side effects among races could not be determined.
- Age: The occurrence of side effects was similar in pediatric patients and adult patients except for vomiting and increased liver enzymes levels, which were seen in more pediatric than adult patients.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
One or more adverse events were reported by 100% of the subjects in the safety population.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.
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