Thymidine kinase 2 deficiency (TK2d) is a very rare genetic disease that causes muscle weakness, which can happen in different parts of your body. TK2d can sometimes be severe and affect your ability to chew and swallow or breathe. TK2d was first reported in the year 2001 in four children who developed severe muscle weakness. Today, only about 600-2,700 people in the U.S. are known to have TK2d. Since it is a relatively new disease and has only happened in a small number of people, much is unknown about how it affects different people. Until recently, there were no medicines approved to treat TK2d. However, in November 2025, the FDA approved Kygevvi (doxecitine and doxribtimine), making it the first medicine approved to treat TK2d.
How Do I Take Kygevvi?
When you receive your prescription for Kygevvi for the first time, you should also receive an administration kit along with your prescription. The kit comes with a mixing bottle to mix up the dose, a cup and two oral syringes that can be used to measure and give the dose, and two extra seals.
Kygevvi comes as a powder packet that is mixed with water and then taken by mouth or through a feeding tube three times per day, about six hours apart, with food. The specific dose that you will take depends on how much you weigh.
An adult should be the one to mix up and give the dose. The powder medicine should only be mixed with room-temperature water. At the time the dose is mixed, you will prepare a full one-day supply of Kygevvi to be used throughout the day. The dosing cup or oral syringe should be rinsed with water and dried after each dose is given. Throw away any remaining medicine after all three doses have been given or if 16 hours have passed since you first mixed it up (whichever happens first). Refer to the product’s instructions for use for more detailed information on how to mix and give the dose of Kygevvi.
After you start Kygevvi, your health care provider may increase the dose after two weeks if you are tolerating it well.
How Will I Be Monitored While Taking Kygevvi?
Before you start Kygevvi, your health care provider will order lab tests, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), to see how well your liver is working. They will also check your total bilirubin levels, which can also show problems with your liver. Any lab values that are taken before you start treatment are called your baseline. Your future lab values will be compared to your baseline to see if anything has gotten worse after you start treatment with Kygevvi.
Since Kygevvi can cause these lab levels to increase, your health care provider will check them every so often while you are taking Kygevvi to make sure they do not increase too much. If your lab values increase too much, your health care provider may temporarily stop Kygevvi until they go back down to your baseline or stabilize (which means they stay at the same level and do not keep getting worse). If your lab values do not get better or continue to get worse, your health care provider may stop Kygevvi.
How Was Kygevvi Studied for TK2d?
The safety and effectiveness of Kygevvi have been evaluated using findings from multiple small, retrospective studies, which utilized data collected in the past. These studies focused on individuals with TK2 deficiency (TK2d) whose symptoms began at or before age 12 and who were treated with Kygevvi or pyrimidine nucleosides. To see how well Kygevvi worked, these studies “matched” each person who got Kygevvi to another person with TK2d who did not get Kygevvi from a study that was done in the past and compared how long they lived. “Matching” means that those who were compared were as alike as possible, and the biggest difference between them was whether or not they got Kygevvi to treat their TK2d.
Overall, these studies included 78 people with TK2d who were treated with Kygevvi. People treated with Kygevvi were 54% male and 36% Hispanic or Latino. Most were White (82%), 4% were Black or African American, 5% were Asian, 3% had a race of “other”, and 1% were American Indian or Alaska Native. People treated with Kygevvi had their TK2d symptoms start at a median age of 1.5 years and received treatment for a median of about four years. A median is the middle value, so half the people in the study had numbers higher than this, and half had lower numbers.
What Did the Studies Find?
Of the 78 people with TK2d who were treated with Kygevvi, only 3.8% (three people) died. In comparison, 35.9% (28 people) with TK2d who did not get treatment died. This means that people with TK2d who got Kygevvi were 86% less likely to die than those who did not get the medicine.
The study researchers also used the findings from these studies to predict how long people would live within 10 years after treatment. Based on these calculations, the researchers estimated that people treated with Kygevvi would live for an extra 9.6 years, compared to 5.7 years in similar people with TK2d who did not get treatment.
Your results may differ from what was seen in clinical studies.
What Other Benefits Were Seen?
Two studies looked at how well people were able to breathe before and after treatment with Kygevvi and compared those findings to those in people who did not take Kygevvi. Some of the main findings are described below.
- People who took Kygevvi had a higher forced vital capacity than people who did not. (Forced vital capacity is a measurement of how much air your lungs can breathe in and out. A larger number means that your lungs are working better.)
- Some people who took Kygevvi were less likely to need help with breathing by using noninvasive ventilation.
In one of the studies, some people who needed a feeding tube to help them eat before starting Kygevvi were able to remove the feeding tube after starting treatment. This means that Kygevvi may have helped them to be able to eat on their own.
The same study found that some people who were treated with Kygevvi gained new muscle abilities after starting treatment. For example, 90% of people who could not hold their head upright without help before treatment were able to do so after receiving Kygevvi.
Your results may differ from what was seen in clinical studies.
How Strong Are the Studies for Kygevvi?
As was mentioned earlier, Kygevvi was studied using retrospective data (which is data that was collected in the past), and the findings were compared between “matched” people. The main drawback to using retrospective data is that the researchers only have access to the information that was collected in the past, and important details could be missing. Even when people are “matched,” there can still be differences between the groups that can affect the study findings. Because of this, retrospective studies such as the ones that were done to examine Kygevvi can suggest that treatment with Kygevvi may be related to a lower risk of death, but cannot confidently say that the lower risk of death is only because of treatment with Kygevvi. There could be other things that were not recorded in the data from the past that may have also lowered the risk of death in the people who were treated with Kygevvi.
What Can I Do to Manage Side Effects?
The most common side effects from Kygevvi are increased liver enzymes (ALT and AST) and stomach problems, such as diarrhea, vomiting (throwing up), and stomach pain. Your health care provider will check your lab results regularly to make sure your liver enzymes do not get too high.
If you have diarrhea or are throwing up, it is important to drink lots of fluids so that you do not become dehydrated. Some signs that you may be dehydrated include dry mouth, dark yellow pee, headache, feeling thirsty, muscle cramps, and shriveled skin.
Make sure to stay well hydrated while taking Kygevvi by drinking plenty of fluids such as water, broth, or oral rehydration solutions such as Gatorade or Pedialyte. On a normal day, you should drink six to eight cups of water or other fluids. If you have diarrhea or are throwing up, electrolyte replacement products can be used to help you stay hydrated.
Eating bland foods that are easy on your stomach, such as bananas, rice, applesauce, and toast (also called the BRAT diet) can also help with stomach problems. Avoid greasy or fatty foods, which can make these side effects worse. If you have diarrhea or vomiting that lasts more than a few days while you are taking Kygevvi, tell your health care provider right away. They may need to temporarily lower your dose of Kygevvi or stop it completely.
Kygevvi can cause serious diarrhea and vomiting. Signs of serious dehydration include not being able to pee (or very dark colored pee), having a fast heartbeat or breathing faster than normal, feeling dizzy, tired, or confused, or not being able to make tears. If you have any of these side effects while you are taking Kygevvi, go to an urgent care center or hospital right away. You may need to be given IV fluids (fluids given directly into your vein) to quickly restore the balance of fluids and electrolytes in your body.