Treatments for Familial Chylomicronemia Syndrome (FCS) You May Not Have Heard About

Familial chylomicronemia syndrome (FCS) is a rare genetic disorder that causes extremely high triglyceride (fat) levels in the blood. Common symptoms include abdominal pain from pancreatitis, enlargement of the liver and spleen, yellow fat deposits in the skin, and a creamy appearance of the blood vessels in the eye.e60dc2a1-f33c-4a05-9b50-8e3e8e597629a90a29fa-b30d-49a8-b02c-899bfbda9977 FCS is typically treated with diet restrictions.e60dc2a1-f33c-4a05-9b50-8e3e8e59762970fda121-a950-4805-a807-eb335b9be5d6 “The most important lifestyle factor [in FCS] is a strict low-fat diet,” says David H. Hsi, MD , chief of cardiology and co-director of the Heart and Vascular Institute at Stamford Health in Connecticut. But the U.S. Food and Drug Administration (FDA) has approved one medication for FCS, and experts are researching other emerging treatments. These new medications block activity that leads to high triglyceride levels and, once approved, could offer life-changing symptom improvement for people with this disorder.e60dc2a1-f33c-4a05-9b50-8e3e8e597629e06e9271-4924-40a6-be39-e06f1b64ffe1 If you want to try a new familial chylomicronemia syndrome treatment, check with your healthcare team first, who can direct you to available options.
FDA-Approved Medications Medications Olezarsen (Tryngolza), the first and only FDA-approved medication for the treatment of FCS, works by blocking the production of apolipoprotein C3 (a protein that inhibits the breakdown of fat), which allows your body to break down fats more easily, says Dr. Hsi.e60dc2a1-f33c-4a05-9b50-8e3e8e597629100e4349-d1c3-409f-9ee1-111ad96acca7 “In our clinic, olezarsen has been effective in decreasing triglycerides,” says Ashish Sarraju, MD , preventive cardiologist at Cleveland Clinic in Ohio. “The hope is that this will translate to reduced risk of pancreatitis (a common complication of FCS) moving forward.” Olezarsen is to be used along with a low-fat diet, and is given as an injection in the fatty part of the abdomen or thigh once a month. Sometimes injections can cause hypersensitivity reactions, which include side effects like swelling, itching, chills, muscle pain, and difficulty breathing.e60dc2a1-f33c-4a05-9b50-8e3e8e59762983533ab9-d3a2-4c24-a3c3-42096c56d186 As a new medication, olezarsen isn’t always available at local pharmacies, says Dr. Sarraju. But your provider can help. After confirming an FCS diagnosis, providers have to work through insurance coverage, which may not be straightforward, says Sarraju. “So, it is important for patients to stay in close touch with their doctors to navigate the insurance.”
Emerging Treatments Emerging Treatments Although the FDA has only approved olezarsen so far, other investigational therapies are being evaluated in clinical trials . “I am excited about therapies that target apolipoprotein C3 and ANGPTL3 as mechanisms to improve triglycerides,” says Sarraju, as both of these proteins stop effective fat breakdown.e60dc2a1-f33c-4a05-9b50-8e3e8e59762977215f9a-2fa1-450f-82b3-bcd79b7529d9 Plozasiran (ARO-APOC3) An experimental drug called plozasiran works by suppressing the genes for apolipoprotein C3, allowing the body to flush out more fat. In a current clinical trial set to wrap up in 2026, 75 people with FCS have had up to an 80 percent decrease in triglyceride levels after taking plozasiran for 10 months.e60dc2a1-f33c-4a05-9b50-8e3e8e5976295b31f675-185d-4b4b-b031-b305072d0c5fe60dc2a1-f33c-4a05-9b50-8e3e8e597629836022a6-fc3d-4c10-a790-9f1be4481772 So far, participants have reported few side effects, but some experienced abdominal pain, sinus inflammation, headache, and nausea.e60dc2a1-f33c-4a05-9b50-8e3e8e59762977215f9a-2fa1-450f-82b3-bcd79b7529d9 Gene Editing Therapies Sometimes FCS is caused by a problem with the ANGPTL3 gene, which gives the ANGPTL3 protein its operating instructions.e60dc2a1-f33c-4a05-9b50-8e3e8e597629e8885157-4e94-4c1c-9f58-bde67adf66d0e60dc2a1-f33c-4a05-9b50-8e3e8e597629f9af0d18-2925-4ee2-a7b6-428f9b6f4ce3 Researchers are studying methods to change how these genes work using a technique called CRISPR, stopping triglyceride-boosting proteins at their source.e60dc2a1-f33c-4a05-9b50-8e3e8e59762977215f9a-2fa1-450f-82b3-bcd79b7529d9 This treatment option is still in its early stages, and animal studies show promise; however, human trials are needed before gene editing can be used to treat FCS.e60dc2a1-f33c-4a05-9b50-8e3e8e597629659f78db-2bf4-4d9c-b519-e2dc0762a27e ANGPTL3 Inhibitors Some emerging medications bypass the genetic component and target the ANGPTL3 protein itself. For example, monoclonal antibodies (proteins made in a lab) attach to specific materials, like ANGPTL3, and destroy them.e60dc2a1-f33c-4a05-9b50-8e3e8e597629a009593d-c378-4f3c-a1d2-e9b111df0793 Monoclonal antibodies being studied for FCS treatment include evinacumab and vupanorsen. Evinacumab was shown to significantly lower LDL levels in phase 3 trials, and vupanorsen reduced triglycerides by up to 53 percent in a phase 2 trial.e60dc2a1-f33c-4a05-9b50-8e3e8e59762977215f9a-2fa1-450f-82b3-bcd79b7529d9 Zodasiran and solbinsiran (siRNA therapies) are another type of ANGPTL3 inhibitor. In phase 2 clinical trials, zodasiran lowered triglycerides by up to about 63 percent, and preliminary trials of solbinisiran demonstrated a reduction of triglycerides by 73 percent.e60dc2a1-f33c-4a05-9b50-8e3e8e59762977215f9a-2fa1-450f-82b3-bcd79b7529d9 Orlistat (Xenical) Orlistat (Xenical) prevents the intestines from absorbing some of the fats you eat.e60dc2a1-f33c-4a05-9b50-8e3e8e59762993260724-bdec-4f40-b8e8-80e0684f0e7c Typically used for obesity treatment , orlistat may also decrease triglyceride levels in FCS.e60dc2a1-f33c-4a05-9b50-8e3e8e597629d9603c6f-989a-482b-8944-8522da31a5c1 One small study of two children found orlistat lowered triglycerides by up to 62 percent.e60dc2a1-f33c-4a05-9b50-8e3e8e59762947e1a1e8-49bd-4664-b427-a2cec5a16e71 In another case study on a 35-year-old woman, treatment with orlistat lowered triglyceride levels and reduced hospital admissions for pancreatitis.e60dc2a1-f33c-4a05-9b50-8e3e8e59762999b8ddc2-ddb4-42ec-8b3b-ce46e0a8e452 When taking orlistat, it’s important to restrict your fat intake, which can cause side effects like excess gas and loose stools. Your body needs some fat to function, and your provider may also recommend taking fat-soluble vitamins to prevent nutrient deficiencies.e60dc2a1-f33c-4a05-9b50-8e3e8e597629d9603c6f-989a-482b-8944-8522da31a5c1
Joining a Clinical Trial Clinical Trials Many of these developing treatment options are offered in ongoing clinical trials, which allow people with FCS to try new medications before they’re available to the public. Your provider can help you find ongoing trials and connect you with experts in that field, says Sarraju. “Any patients with FCS should seek specialized care in lipid management, such as a certified dietitian and lipid specialist,” says Hsi. Another good source of information on emerging treatments is ClinicalTrials.gov , an online research database maintained by the U.S. government. Here, you can search for studies on FCS or specific treatments, find out what stage of the process they’re in, and discover trials currently accepting applicants.
The Takeaway Familial chylomicronemia syndrome is primarily treated with a very low-fat diet, but the FDA has recently approved a drug called olezarsen (Tryngolza), which can work alongside diet to decrease FCS symptoms and complications. Some emerging treatments target the proteins that cause FCS, and others edit the DNA responsible for encoding these proteins. If you’re interested in joining a clinical trial for an FCS medication that’s not yet available to the public, you can find ongoing trials at ClinicalTrials.gov.
Resources We Trust Mayo Clinic: Olezarsen (subcutaneous route)Cleveland Clinic: HypertriglyceridemiaFCS Foundation: FCS ResourcesNational Organization for Rare Disorders: Familial Chylomicronemia SyndromeEndocrine Society Familial Chylomicronemia Syndrome

Source link