What Is Koselugo, and Why Does It Matter?
Koselugo (selumetinib) is an oral medicine that helps slow the growth of certain tumors. The FDA has approved it for adults with neurofibromatosis type 1 (NF1) who have tumors called plexiform neurofibromas (PN) that are symptomatic and cannot be surgically removed. Koselugo works by blocking two enzymes, MEK1 and MEK2, that can become overactive in people with NF1, leading to the growth of noncancerous plexiform neurofibromas. Another MEK inhibitor, mirdametinib (Gomekli), is also approved in the U.S. for NF1 in adults and children ages 2 years and older.
NF1 is a rare genetic condition caused by either spontaneous or inherited changes in the NF1 gene. It affects about 1 in every 3,000 people and usually begins in childhood. Almost half of the people with NF1 may develop PN, which can affect their brain, spinal cord, and nerves. These PN may also develop later in life, growing quite large and causing pain, changes in appearance, muscle weakness, and problems with movement or organ function. These tumors often can't be removed with surgery because of their location or the way they grow.
Koselugo was first approved for children as young as 1 year of age who have symptoms due to inoperable PN. The FDA has now approved it for adults with the same condition. This approval matters as it allows people with NF1 to continue with the same treatment as they grow older, which ensures long-term care.
Why Was It Approved?
Koselugo was approved for adults with NF1 and inoperable PN based on clinical studies that showed it could shrink tumors, provide significant pain relief, and lower the need for pain medications.
The study included 145 adults with inoperable PN who had ongoing pain and tumors that could be measured using MRI. Results showed that 20% of people who took Koselugo, versus 5% of those in the placebo group, had a noticeable shrinkage in their tumors – at least a 20% reduction in size. Among those who responded to Koselugo, 86% of patients continued to improve for at least six months. On average, it took about 3.7 months to see a response.
The most common side effects in adults are rash, acne-like skin irritation (dermatitis acneiform), and diarrhea. Some serious side effects include heart problems, eye issues, an increased risk of bleeding, and muscle damage due to high levels of a muscle enzyme or a condition called rhabdomyolysis, which can cause muscle breakdown.
What Do I Need to Know?
You take Koselugo twice a day by mouth. The dose depends on your body size and how well your liver works. It comes in the form of capsules or oral granules. You must swallow the capsules whole without opening, chewing, or crushing them. If you use the granules, you can mix them with soft foods like yogurt or fruit puree. Don't mix them with fruit juices, drinks, or any food item containing grapefruit or Seville oranges. Be sure to eat the mixture within 30 minutes.
If you throw up after taking a dose, don't take another one. Just wait until your next scheduled dose. If you miss a dose and it's less than six hours before your next one, skip the missed dose.
Before starting Koselugo, your health care provider will check your heart and eyes. These checks will continue during treatment. Koselugo can cause serious side effects, including heart problems, vision changes, muscle damage, and a higher risk of bleeding – especially if you take blood thinners, medicines to treat blood clots, or vitamin E supplements. If side effects become serious, your provider may lower the dose or stop the medicine.
Before taking Koselugo, tell your health care provider if you have heart, liver, or eye problems. Be sure to tell your provider about all the medicines you take, including prescription and over-the-counter medicines such as aspirin, herbal supplements, and vitamins. Certain medicines that affect how your liver processes drugs can change how Koselugo works in your body. Avoid having grapefruit, Seville oranges, and St. John's wort during your treatment.
If you can become pregnant, your health care provider will check for pregnancy before starting Koselugo as the medicine can harm a fetus. You should use reliable birth control during treatment and for a week after the last dose. Tell your provider right away if you become pregnant or think you might be pregnant during treatment. Men with partners who can become pregnant should also use effective birth control during treatment and for a week afterward. Do not breastfeed while taking Koselugo or for a week after the last dose; talk to your doctor about safe feeding options for your baby.
Contact your health care provider right away if you notice swelling of your ankles and feet; a faster heartbeat; coughing or trouble breathing; diarrhea; a widespread or itchy rash; skin bumps that look like acne; blisters or peeling skin; eye or vision problems; muscle aches, spasms, or weakness; or dark reddish urine. These could be signs of serious side effects.