What Is Imcivree, and Why Does It Matter?
Imcivree (setmelanotide) is an injectable medication used for treating a rare type of obesity linked to Bardet-Biedl syndrome and certain genetic conditions. The FDA has now approved Imcivree for a broader use to treat acquired hypothalamic obesity (HO) in adults and children ages 4 years and older, helping them reduce extra body weight and keep it off in the long term.
Acquired HO is a rare condition caused by damage or injury to the hypothalamus (a part of the brain that regulates hunger and energy balance), leading to rapid and lasting weight gain. This damage can reduce levels of alpha-melanocyte-stimulating hormone, disrupting the melanocortin-4 receptor (MC4R) pathway, which regulates body weight. Acquired HO often happens after the growth or treatment of tumors near the hypothalamus, such as a craniopharyngioma or astrocytoma, or due to a brain injury, stroke, or inflammation. As a result, affected people often gain weight quickly, may have extreme hunger, and may burn fewer calories, sometimes as early as six months after the brain injury. About 10,000 people in the U.S. are estimated to have this condition.
Imcivree is an MC4R agonist that selectively turns on MC4R signals in the brain and helps manage hunger, appetite, the feeling of fullness, and how your body uses energy. Scientific studies suggest that Imcivree can restore the MC4R signaling pathway in acquired HO, lowering appetite and increasing energy use. Thus, Imcivree aims to reduce hunger, helping affected people eat less and support their long-term weight loss journey by targeting the cause of their condition.
Imcivree was first approved in 2020 and is also used to treat adults and children 2 years and older with certain rare forms of obesity linked to Bardet-Biedl syndrome and conditions with specific changes in the POMC, PCSK1, or LEPR genes, which are confirmed through genetic testing.
This approval is important because Imcivree is the first and only FDA-approved medicine that offers a targeted therapy for acquired HO.
Why Was It Approved?
The FDA’s decision was based on data from clinical trials that showed that Imcivree was generally well tolerated and effective in reducing weight and lowering hunger in adults and in children ages 4 years and older with acquired HO, whereas those on a placebo gained weight.
The results of a phase 3 study of 142 patients with acquired HO showed that after 52 weeks, patients who took Imcivree had an average 15.84% decrease in their body mass index (BMI), compared with an average 2.55% increase in the BMI of those who took a placebo, resulting in a placebo-adjusted average BMI reduction of 18.4%. People on Imcivree also reported having less hunger at 52 weeks, compared with those on a placebo.
The most common side effects of this medicine were darkening of the skin (hyperpigmentation), darkening of existing moles and the appearance of new moles, reactions where the needle went in, nausea, vomiting, and headaches. Serious side effects such as spontaneous and more frequent erections in male patients, depression, and severe allergic reactions have also been reported.
In people with acquired HO who already have secondary adrenal insufficiency, a sudden adrenal crisis (acute adrenal insufficiency), in which the adrenal glands stop working, has been known to happen. In patients with acquired HO and central diabetes insipidus (also known as arginine vasopressin deficiency), changes in blood sodium levels have been reported.
What Do I Need to Know?
Imcivree is injected under the skin once each morning with or without food. Use the belly area, thigh, or upper arm, and switch spots every day. Do not inject until a health care provider trains you or your caregiver on how to prepare and give the dose. If you or your child misses a dose, take the next shot at the scheduled time on the next day.
Let your health care provider know if you or your child has or has had areas of darkened skin, including skin discoloration (hyperpigmentation); kidney problems; or suicidal thoughts or behavior. Before using it, tell your health care provider if you are allergic to setmelanotide or any other ingredients in the product.
Your health care provider may recommend a full-body skin exam before starting and during treatment with Imcivree to monitor any changes in your or your child’s skin. Be sure to tell your health care provider if you or your child has acquired HO along with adrenal insufficiency, and ask your care team about sick‑day steroid plans. (During treatment, some people may need changes in steroid doses during illness, fever, injury, or infections.) Your health care provider will monitor your or your child’s blood sodium levels during treatment if you or your child has acquired HO with central diabetes insipidus.
Be sure to let your health care provider know about all medicines you or your child uses – including prescription and over-the-counter medicines, vitamins, and herbal supplements – to avoid any harmful interactions. Your health care provider may adjust your or your child’s medicines if needed.
Tell your health care provider if you are pregnant, planning to become pregnant, or breastfeeding. Do not breastfeed while using Imcivree as it is not known whether Imcivree passes into your breast milk. If you become pregnant, your health care provider may stop treatment because losing weight in pregnancy can harm a fetus.
This medicine is not for other types of obesity that are not related to acquired HO; Bardet-Biedl syndrome; or POMC, PCSK1, or LEPR deficiencies, including obesity related to other genetic syndromes and general (polygenic) obesity.
Call your health care provider right away if you have suicidal thoughts; notice new or worse symptoms of depression or any sudden mood or behavior changes; have signs of an allergic reaction (including breathing problems; swelling of the face, lips, mouth, tongue, or throat; dizziness or a feeling of lightheadedness; itching; hives; or a skin rash); have signs of an infection or changes in the amount of fluids you take or urine you pass; or if you have tiredness, exhaustion, or confusion during the treatment. Get emergency care for an erection lasting more than four hours.
The drugmaker reports that Imcivree will be available in the U.S. right away, along with support for access, insurance, and injection training.