お知らせ • Jun 25
Ionis Pharmaceuticals Announces Fda Approval of Tryngolza (Olezarsen) as First and Only Treatment to Reduce Triglycerides and Risk of Acute Pancreatitis in Patients with Severe Hypertriglyceridemia
Ionis Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved TRYNGOLZA (olezarsen) as an adjunct to diet to reduce triglycerides (TG) and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG: TG greater than or equal to 500 mg/dL). TRYNGOLZA is available in a 50 mg or 80 mg dose and is self-administered once monthly via an autoinjector. sHTG is characterized by an increased risk of acute pancreatitis, which causes debilitating abdominal pain that often leads to repeated and prolonged hospitalization, permanent organ damage and can be life-threatening. TRYNGOLZA is the only treatment for sHTG indicated to reduce the risk of acute pancreatitis. The FDA approval was based on positive results from the Phase 3 CORE and CORE2 studies, which were published in The New England Journal of Medicine. In the CORE and CORE2 studies, TRYNGOLZA demonstrated rapid and consistent triglyceride control, lowering fasting triglyceride levels by up to 72% compared to placebo at six months and sustaining those reductions at 12 months. Additionally, TRYNGOLZA significantly reduced acute pancreatitis events by up to 91%. Among patients treated with TRYNGOLZA with baseline and 12-month data, 86% achieved triglyceride levels below 500 mg/dL, a critical threshold for reducing acute pancreatitis risk. The number needed to treat (NNT) over one year to prevent one episode of acute pancreatitis was 20 in the overall cohort and four in patients with triglycerides =880 mg/dL and a prior history of acute pancreatitis, indicating a strong clinical benefit across the spectrum of sHTG patients and an exceptional clinical benefit in the highest risk subgroup. Across the clinical program, TRYNGOLZA demonstrated a favorable safety and tolerability profile. The most common adverse reactions in patients with sHTG (incidence =2% higher than placebo) were injection site reactions and liver enzyme increases. TRYNGOLZA (olezarsen) is indicated as an adjunct to diet to reduce triglycerides (TG) in adults with familial chylomicronemia syndrome (FCS). TRYNGOLZA is indicated as an adjunct to diet to reduce TG and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG: TG =500 mg/dL). TRYNGOLZA is contraindicated in patients with a history of serious hypersensitivity to TRYNGOLZA or any of the excipients in TRYNGOLZA. Hypersensitivity reactions requiring medical treatment have occurred. Hypersensitivity reactions (including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills, and myalgias) have been reported in patients treated with TRYNGOLZA. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of TRYNGOLZA if hypersensitivity reactions occur. TRYNGOLZA can cause increases in liver enzymes and hepatic fat in adults. Increases in liver enzymes were more frequently reported with the 80 mg dose as compared with the 50 mg dose. Consider liver enzyme testing before TRYNGOLZA initiation or an increase in dosage and when clinically indicated thereafter. If persistent elevations in liver enzymes occur, consider dose interruption and/or dose reduction. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue TRYNGOLZA. Most common adverse reactions in patients with FCS (incidence >5% of TRYNGOLZA-treated patients and >3% higher frequency than placebo) were injection site reactions, decreased platelet count, and arthralgia. Most common adverse reactions in patients with sHTG (incidence =2% higher than placebo) were injection site reactions and liver enzyme increases. CORE (NCT05079919; n=617) and CORE2 (NCT05552326; n=446), conducted with The TIMI Study Group, are Phase 3 global, multicenter, randomized, double-blind, placebo-controlled trials investigating the safety and efficacy of olezarsen for severe hypertriglyceridemia (sHTG). Participants aged 18 and older with triglyceride levels =500 mg/dL were enrolled. Participants were required to be on standard of care therapies for elevated triglycerides. At baseline, 47% and 37% of participants had fasting triglycerides =880 mg/dL in CORE and CORE2, respectively. Participants were randomized to receive 50 mg or 80 mg of olezarsen or placebo every four weeks via subcutaneous injection for 12 months. The CORE and CORE2 studies met the primary endpoint, with both 50 mg and 80 mg monthly TRYNGOLZA doses. TRYNGOLZA demonstrated a statistically significant reduction in fasting triglycerides of 49%-63% (50 mg) and 55%-72% (80 mg) compared to placebo at six months. Additionally, TRYNGOLZA demonstrated a statistically significant 91% (50 mg) and 76% (80 mg) reduction in acute pancreatitis events at 12 months, with a pooled reduction of 85%. Severe hypertriglyceridemia (sHTG) is defined by very high triglycerides (=500 mg/dL) and characterized by an increased risk of acute pancreatitis and other serious health complications. Acute pancreatitis causes debilitating abdominal pain that often requires prolonged hospitalization, can lead to permanent organ damage and can become life-threatening. Preventing the first attack is key. In people with a history of acute pancreatitis episodes, the risk of future attacks is even greater. Current standard of care therapies for sHTG and lifestyle modifications (such as diet and exercise) do not sufficiently or consistently lower triglyceride levels or reduce the risks of sHTG in all patients. More than 3 million people are living with sHTG in the U.S., including approximately 1 million who are considered high risk. High-risk sHTG includes those with triglycerides =880 mg/dL or triglycerides =500 mg/dL and a history of acute pancreatitis or other comorbidities. TRYNGOLZA (olezarsen) is an RNA-targeted therapy designed to lower the body's production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood. TRYNGOLZA is approved in the United States as an adjunct to diet to reduce triglycerides (TG) and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG: TG greater than or equal to 500 mg/dL). TRYNGOLZA is also approved in the United States, European Union and other countries for adults with familial chylomicronemia syndrome (FCS), a rare form of sHTG.
