Modeyso (Dordaviprone) as First Treatment for Recurrent H3 K27M-Mutant Diffuse Midline Glioma

Modeyso (dordaviprone) is a new oral medicine that treats a rare and aggressive brain tumor, called diffuse midline glioma (DMG), that has a tumor mutation known to promote tumor growth, called an H3 K27M mutation. This type of tumor mostly affects children and young adults and grows in the central parts of the brain and spinal cord.

Modeyso is the first and only FDA-approved treatment for adults, teens, and children ages 1 year and older with H3 K27-mutant DMG. It offers a new option for those whose disease has progressed despite earlier treatment.

This medicine works to stop the tumor cells from growing or even kill the cancer cells by blocking a protein that promotes cancer growth, cutting off the energy supply to tumor cells, and correcting harmful genetic changes that drive the cancer. About 2,000 people in the U.S. are diagnosed with H3 K27-mutant DMG each year, many of them children. The disease tends to get worse quickly and has a poor outlook.

Why Was It Approved?

Modeyso was approved through the FDA’s accelerated approval program, which allows earlier access to promising treatments for serious conditions. This type of approval is based on early results, and continued approval will depend on future studies that confirm how well the medicine works over time.

Tumors became smaller in about 1 in 5 people with recurring H3 K27-mutant DMG who had already received standard treatments like radiation. For them, the benefits lasted around 10 months on average. Some people had results that lasted more than a year.

In studies, the most common side effects of Modeyso included tiredness, headaches, nausea, vomiting, and muscle or joint pain. About one-third of people had serious side effects, such as fluid buildup in the brain, seizures, muscle weakness, and heart rhythm problems. A few people had life-threatening reactions like severe allergic responses and heart issues.

What Do I Need to Know?

Take Modeyso by mouth once a week on an empty stomach — either at least one hour before eating or three hours after. For children, the dose depends on their weight. If swallowing capsules is hard, the contents can be mixed with 15-30 mL of liquid (sports drink, apple juice, lemonade, or water) before taking.

Modeyso can cause allergic reactions and heart rhythm problems. Your health care provider will perform a heart test and check certain blood levels before and during treatment. Modeyso may also cause harm to a fetus if used during pregnancy. You should not take this medicine if you are pregnant or breastfeeding. Both men and women should use birth control while taking Modeyso and for at least one month after the last dose.

Modeyso can also interact with other medicines, including those that also cause heart rhythm problems. Be sure to tell your health care provider about all the medicines you take, including over-the-counter drugs and supplements, to avoid harmful interactions.