Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Mipomersen · 12 trials · 22 indications
LDL-C was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides \>=400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
LDL cholesterol was measured in mg/dL. Samples were taken following an overnight fast. LDL-C was obtained using Friedewald's calculation for patients with triglycerides ≤400 mg/dL and was directly measured by the central laboratory using ultracentrifugation for patients with triglycerides \>400 mg/dL. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
The on-treatment time frame spanned the time during which the study drug was administered until the later of the primary efficacy time point and 14 days beyond the last study drug date. Adverse events (AEs) were considered related if assessed by the Investigator as possibly, probably or definitely related to study drug. Severity was assessed as: * Mild-symptom barely noticeable to the patient or do not make the patient uncomfortable; * Moderate-symptom makes the patient uncomfortable, affects performance of daily activities; * Severe-symptom causes the patient severe discomfort, may cause cessation of treatment with the study drug. Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention.
LDL cholesterol was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Localized proton MRS was used to quantify liver TG concentration. All MRS imaging of the liver was performed using the same 1.5T scanner. The instructions were to cover the entire liver (from just above the dome to just below the inferior tip) using a qualified imaging technique (Yokoo, 2009, Radiology). Liver fat quantification was performed by determining the liver fat fraction (%) derived from MRS using selected Regions of Interest (ROI). The analyst typically looked for the branching of the right portal vein and mapped slices from one scan to the next. There were typically 2 ROIs in the right lobe and 1 in the left lobe. Magnetic resonance spectroscopy imaging ROIs between different scans were selected using anatomical landmarks for both time points.
plasma PK parameters
plasma PK parameters
plasma PK parameters
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | Weekly subcutaneous injections for 26 weeks |
| Mipomersen | EXPERIMENTAL | 200 mg weekly subcutaneous injections for 26 weeks |
| Mipomersen 200 mg per week | EXPERIMENTAL | Participants received 200 mg mipomersen once a week by subcutaneous injection, for up to 3 years. |
| Mipomersen 200 mg every other week | EXPERIMENTAL | Participants received 200 mg mipomersen every other week by subcutaneous injection, for up to 3 years. Participants could receive mipomersen 200 mg once a week at the Investigator's discretion after the first 52 weeks of the treatment period. |
| Cohort A: mipomersen | EXPERIMENTAL | Healthy volunteers treated with 6 injections of mipomersen 200 mg over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
| Cohort A: placebo | PLACEBO_COMPARATOR | Healthy volunteers treated with 6 injections of placebo over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
| Cohort D: mipomersen | EXPERIMENTAL | Participants with impaired fasting glucose and mixed dyslipidemia who were treated with 6 injections of mipomersen 200 mg over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
| Cohort D: placebo | PLACEBO_COMPARATOR | Participants with impaired fasting glucose and mixed dyslipidemia who were treated with 6 injections of placebo over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
| Cohort E: mipomersen | EXPERIMENTAL | Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly mipomersen 200 mg injections for 13 weeks. |
| Cohort E: placebo | PLACEBO_COMPARATOR | Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly placebo injections for 13 weeks. |
| Cohort F: no intervention | NO_INTERVENTION | A reference group of participants with familial hypobetalipoproteinemia (FBHL) who did not receive a study intervention. Data gathered for 15 weeks. |
| Cohort G: mipomersen | EXPERIMENTAL | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| Cohort G: placebo followed by mipomersen | PLACEBO_COMPARATOR | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with placebo weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| mipomersen IV (supra-therapeutic dose) | EXPERIMENTAL | 200 mg of mipomersen IV / placebo SC |
| mipomersen SC (therapeutic dose) | EXPERIMENTAL | 200 mg of mipomersen SC / placebo IV |
| moxifloxacin IV | ACTIVE_COMPARATOR | 400 mg of moxifloxacin IV / placebo SC |
| Name | Type | Description |
|---|---|---|
| Mipomersen | DRUG | 200 mg (1 mL), weekly subcutaneous injections for 26 weeks |
| Placebo | DRUG | 1 mL weekly subcutaneous injections for 26 weeks |
| Mipomersen sodium | DRUG | 200 mg/mL |
| moxifloxacin hydrochloride (Avelox®) | DRUG | 400 mg of moxifloxacin intravenous (IV) single dose |
Inclusion Criteria: * Fasting LDL-C ≥200 mg/dL (5.1 mmol/L) at screening and the presence of at least 1 of the following criteria: * Myocardial infarction (MI) * Percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) * Coronary artery disease documented by angiograph...
Mipomersen is an investigational small molecule being developed for cardiovascular conditions, including heterozygous familial hypercholesterolemia, hypercholesterolemia, and lipid metabolism disorders. It has been studied in healthy volunteers and in patients with these metabolic diseases. The drug is administered via subcutaneous injection and is currently in Phase 3 clinical development.
Mipomersen is being developed by Ionis Pharmaceuticals, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol IONS. The company has conducted clinical trials evaluating the drug's safety, efficacy, and pharmacokinetics in various patient populations and healthy volunteers.
Mipomersen is in Phase 3 clinical development. It has completed four clinical trials, including Phase 1 and Phase 2 studies. The drug is investigational and has not been approved by regulatory authorities. All completed trials were randomized, double-blind, and placebo-controlled, with a total enrollment of 254 participants.
Mipomersen has completed four clinical trials. NCT00707746 was a Phase 2 study in high-risk statin-intolerant subjects with hypercholesterolemia. NCT01061814, NCT01090661, and NCT01299298 were Phase 1 studies in healthy volunteers, including a cardiac repolarization study and a pharmacokinetic study in Japanese healthy volunteers.
Mipomersen is an antisense oligonucleotide that targets apolipoprotein B-100, a key protein involved in lipid metabolism. By inhibiting the production of this protein, the drug aims to reduce levels of atherogenic lipoproteins, including LDL cholesterol. This mechanism is relevant for treating conditions like familial hypercholesterolemia and other lipid metabolism disorders.