Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as mipomersen sodium, ISIS 301012, Kynamro™
mipomersen · 12 trials · 21 indications
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. 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.
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).
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Mipomersen | EXPERIMENTAL | Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants received a placebo subcutaneous injection once a week for 26 weeks. |
| Cohort A | EXPERIMENTAL | Loading doses followed by weekly maintenance doses |
| Cohort B | EXPERIMENTAL | Loading doses followed by weekly maintenance doses |
| Cohort C | EXPERIMENTAL | Loading doses followed by weekly maintenance doses |
| Cohort D | EXPERIMENTAL | Loading doses followed by extended weekly maintenance doses |
| 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 E | EXPERIMENTAL | Loading doses followed by weekly maintenance doses |
| Cohort F | EXPERIMENTAL | Loading doses followed by extended weekly maintenance doses |
| Cohort G | EXPERIMENTAL | Loading doses followed by extended weekly maintenance doses |
| 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. |
| A | EXPERIMENTAL | Slow load with every other week maintenance |
| B | EXPERIMENTAL | Slow load with every other week maintenance |
| C | EXPERIMENTAL | No load; once weekly maintenance |
| D | EXPERIMENTAL | No load; once weekly maintenance |
| E | EXPERIMENTAL | No load; once weekly maintenance |
| Name | Type | Description |
|---|---|---|
| mipomersen sodium | DRUG | 200 mg /mL |
| placebo | DRUG | 1 mL matching placebo |
| Mipomersen | DRUG | 200 mg (1 mL), weekly subcutaneous injections for 26 weeks |
| ISIS 301012 or Placebo | DRUG | 50 mg subcutaneous injections on days 1, 4, 8, 11, 15, 22, 29, and 36 |
| ISIS 301012 | DRUG | 100 mg subcutaneous injections on days 1, 4, 8, 11, 15, 22, 29, and 36 |
Inclusion Criteria: * Diagnosis of Heterozygous Familial Hypercholesterolemia (HeFH) * Diagnosis of Coronary Artery Disease (CAD) * Stable lipid-lowering therapy for 12 weeks * On maximally tolerated statin therapy with at least 1 statin at a dose greater than zero, per Investigator judgment * Stab...
Mipomersen is an investigational RNA therapy developed for heterozygous familial hypercholesterolemia and other forms of hypercholesterolemia, including patients with lipid metabolism disorders and coronary heart disease. It is designed as an add-on therapy for high-risk patients who need additional lipid lowering beyond standard regimens.
Mipomersen is an antisense inhibitor that targets apolipoprotein B, or APOB. By binding to APOB messenger RNA, it reduces the production of apolipoprotein B, a key structural protein of LDL cholesterol and other atherogenic lipoproteins. Lowering APOB production is intended to reduce circulating LDL cholesterol levels.
Mipomersen is developed by Ionis Pharmaceuticals, Inc., which trades under the ticker IONS. The company is the sponsor of the clinical development program for the drug.
Mipomersen is in Phase 3 clinical development. It is an investigational agent and has not been approved by the FDA. The program includes completed Phase 2 and Phase 3 trials, with no active trials currently listed.
Mipomersen has been studied in four completed trials. These include NCT00794664 in severe hypercholesterolemia, NCT00770146 as add-on therapy in high-risk hypercholesterolemic patients, NCT00707746 in statin-intolerant subjects, and NCT00706849 in heterozygous familial hypercholesterolemia with coronary artery disease.
Yes, mipomersen is also known as mipomersen sodium. The two names refer to the same investigational antisense inhibitor developed by Ionis Pharmaceuticals for hypercholesterolemia and related lipid disorders.