近日，由美国食品和药物管理局（FDA）批准TEGSEDI(inotersen injection) ，TEGSEDI是第一个也是唯一一个皮下RNA靶向治疗药物，为患者提供治疗hATTR淀粉样变性多发性神经病的有效方法。
TEGSEDI是一种透明，无色至淡黄色溶液，在带有SSD的单剂量预装注射器中提供。填充TEGSEDI的每个预填充注射器以递送1.5mL含有284mg inotersen（相当于300mg inotersen钠盐）的溶液。
FDA Approval of TEGSEDI™ (inotersen) for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults
U.S. Food and Drug Administration (FDA) has approved TEGSEDITM (inotersen) for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. TEGSEDI is now approved in the U.S., European Union and Canada.
“TEGSEDI is the first and only RNA-targeting therapeutic that powerfully reduces the production of TTR protein through a once-weekly subcutaneous injection offering patients an effective treatment for people living with polyneuropathy caused by hATTR amyloidosis. We believe this profile will make TEGSEDI an excellent choice for many patients and that it’s self-administration gives the flexibility to treat at a time that works for them which could change the way this progressive and debilitating disease is treated and managed,” said Paula Soteropoulos, chief executive officer at Akcea Therapeutics. “As we execute on our multi-country launch, we are committed to delivering a comprehensive treatment experience for people taking TEGSEDI. Beyond the drug itself, this includes ensuring patients who need this therapy have access to it, offering personalized support programs and enabling patients to administer treatment on their own terms.”
ABOUT TEGSEDITM (INOTERSEN)
TEGSEDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. TEGSEDITM (inotersen), discovered and developed by Ionis Pharmaceuticals, is the world’s first and only subcutaneous RNA-targeting drug designed to reduce the production of human transthyretin (TTR) protein. TEGSEDI also received marketing authorization in the European Union and Canada for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR).
The approval is based on data from the NEURO-TTR study that was a Phase 3 randomized (2:1), double-blind, placebo-controlled, 15-month, international study in 172 patients with hATTR amyloidosis with symptoms of polyneuropathy. In NEURO-TTR, TEGSEDI demonstrated significant benefit compared to placebo in measures of neuropathy and quality of life as measured by the modified Neuropathy Impairment Score +7 (mNIS+7) and in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) total score. Patients treated with TEGSEDI experienced similar benefit regardless of subgroups such as age, sex, race, region, Neuropathy Impairment Score (NIS), Val30Met mutation status, and disease stage.
The approval is also based on data from the NEURO-TTR Open Label Extension (OLE) that is an ongoing study for patients who completed the NEURO-TTR study, designed to evaluate the long-term efficacy and safety of TEGSEDI.
IMPORTANT SAFETY INFORMATION
TEGSEDI can cause serious side effects including:
Low platelet counts (thrombocytopenia): TEGSEDI may cause the number of platelets in your blood to be reduced. This is a common side effect of TEGSEDI. When your platelet count is too low, your body cannot form clots. You could have serious bleeding that could lead to death. Call your healthcare provider immediately if you have:
Unusual bruising or a rash of tiny reddish-purple spots, often on the lower legs
Bleeding from skin cuts that does not stop or oozes
Bleeding from your gums or nose
Blood in your urine or stools
Bleeding into the whites of your eyes
Sudden severe headaches or neck stiffness
Vomiting or coughing up blood
Abnormal or heavy periods (menstrual bleeding)
Kidney inflammation (glomerulonephritis): Your kidneys may stop working properly. Glomerulonephritis can lead to severe kidney damage and kidney failure that need dialysis. Call your healthcare provider immediately if you have:
Puffiness or swelling in your face, feet, or hands
New onset or worsening shortness of breath and coughing
Blood in your urine or brown urine
Foamy urine (proteinuria)
Passed less urine than usual
Because of the risk of serious bleeding caused by low platelet counts and because of the risk of kidney problems, TEGSEDI is available only through a restricted program called the TEGSEDI Risk Evaluation and Mitigation Strategy (REMS) Program. Talk to your healthcare provider about how to enroll in the TEGSEDI REMS Program.
Do not use TEGSEDI if you have:
A platelet count that is low
Had kidney inflammation (glomerulonephritis) caused by TEGSEDI
Had an allergic reaction to inotersen or any of the ingredients in TEGSEDI. See the end of the Medication Guide for a complete list of ingredients in TEGSEDI
Before you start TEGSEDI, tell your healthcare provider about all of your health issues, including if you:
Have or had bleeding problems
Have or had kidney problems
Are pregnant or plan to become pregnant. It is not known if TEGSEDI can harm your unborn baby
Are breastfeeding or plan to breastfeed. It is not known if TEGSEDI can pass into your breast milk or harm your baby. Talk with your healthcare provider about the best way to feed your baby while you are taking TEGSEDI
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take vitamin A or beta-carotene supplements, blood thinners (anticoagulants), or drugs that affect blood clotting.
Your healthcare provider will test your blood and urine to check your platelet counts and kidney and liver function before you start TEGSEDI. While you are receiving TEGSEDI, you will be monitored closely for symptoms, which includes checking your platelet counts every week (or more frequently as needed), kidney function every 2 weeks, and liver function every 4 months. If your healthcare provider has you stop taking TEGSEDI, you will need to continue to get your blood and urine tested for 8 more weeks after treatment.
TEGSEDI may cause serious side effects, including:
Stroke. TEGSEDI may cause a stroke. One person taking TEGSEDI had a stroke, which occurred within 2 days after the first dose. Get emergency help immediately if you have symptoms of stroke, including sudden numbness or weakness, especially on one side of the body; severe headache or neck pain; confusion; problems with vision, speech, or balance; droopy eyelids.
Inflammatory and immune system problems. Some people taking TEGSEDI had serious inflammatory and immune system problems. Symptoms of inflammatory and immune system problems included unexpected change in walking, weakness and spasms in legs, back pain, weight loss, headache, vomiting, and problems with speech.
Liver effects. TEGSEDI may cause liver problems. Your healthcare provider should do laboratory tests to check your liver before you start TEGSEDI and while you are using it. Tell your healthcare provider if you have symptoms that your liver may not be working right, which could include unexpected nausea and vomiting, stomach pain, being not hungry, yellowing of the skin, or having dark urine.
Allergic reactions. TEGSEDI may cause serious allergic reactions. These allergic reactions often occur within 2 hours after injecting TEGSEDI. Get emergency help immediately if you have any symptoms of a serious allergic reaction, including joint pain, chills, redness on palms of hands, muscle pain, chest pain, flushing, tremor or jerking movements, flu-like symptoms, high blood pressure, or difficulty swallowing.
Eye problems (low vitamin A levels). Treatment with TEGSEDI will lower the vitamin A levels in your blood. Your healthcare provider will tell you how much supplemental vitamin A to take every day; only take the amount they tell you to take. Call your healthcare provider if you get eye problems, such as having difficulty seeing at night or in low-lit areas (night blindness).
The most common side effects of TEGSEDI include injection site reactions (such as redness or pain at the injection site), nausea, headache, tiredness, low platelet counts (thrombocytopenia), and fever. These are not all of the possible side effects of TEGSEDI. Talk to your healthcare provider about any side affects you may be experiencing.