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Losmapimod · 2 trials · 2 indications
Skeletal muscle biopsies were collected at Baseline and post-Baseline. DUX4 activity in skeletal muscle biopsies was assessed by measuring expression levels of a panel of 6 genes known to be regulated by DUX4. Expression levels of genes were measured using a validated quantitative RT-PCR assay and expressed as Ct (PCR cycles). Raw Ct for each of the 6 genes was normalized to the specified reference genes to generate a normalized Ct. The DUX4 activity is the average of the normalized Cts of each of the identified 6 genes, where the Ct for each of the 6 genes is first normalized to reference genes before the average is generated. Change in Baseline is calculated as \[average delta Ct across the 6 genes post-baseline\] minus \[average delta Ct across the 6 genes at baseline\].
To assess the bioavailability of losmapimod (1 x 15 mg tablet) (test) versus losmapimod tablets (2 x 7.5 mg tablets) (reference), blood samples will be collected under fasted conditions to measure the plasma concentration of losmapimod at specified timepoints by liquid chromatography with tandem mass spectrometry.
To assess the effect of food on the pharmacokinetics of losmapimod test versus reference, blood samples will be collected under fasted conditions to measure the plasma concentration of losmapimod at specified timepoints by liquid chromatography with tandem mass spectrometry.
| Arm | Type | Description |
|---|---|---|
| Treatment | EXPERIMENTAL | FSHD1 patients with genetic confirmation will receive Losmapimod 15 mg twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 48 weeks. |
| Placebo | PLACEBO_COMPARATOR | FSHD1 patients with genetic confirmation will receive a Placebo twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 48 weeks. |
| Losmapimod 15 mg oral tablet in healthy subjects (Treatment Regimen A) | EXPERIMENTAL | Subjects will be randomized to 1 of 6 treatment sequences to receive one 15 mg tablet of losmapimod administered orally under fasted conditions. Subjects will fast overnight (nothing to eat or drink except water) for at least 10 hours before each study drug administration. Subjects will remain fasted for 4 hours after dosing with study drug. Washout period of 48 hours between dosing. |
| Losmapimod two 7.5 mg oral tablets in healthy subjects (Treatment Regimen B) | EXPERIMENTAL | Subjects will be randomized to 1 of 6 treatment sequences to receive two 7.5 mg tablets of losmapimod administered orally under fasted conditions. Subjects will fast overnight (nothing to eat or drink except water) for at least 10 hours before each study drug administration. Subjects will remain fasted for 4 hours after dosing with study drug. Washout period of 48 hours between dosing. |
| Losmapimod one 15 mg oral tablet in healthy subjects (Treatment Regimen C) | EXPERIMENTAL | Subjects will be randomized to 1 of 6 treatment sequences to receive one 15 mg tablet of losmapimod administered orally under fed conditions. Subjects will fast overnight (nothing to eat or drink except water) for at least 10 hours before breakfast and will receive a high-fat breakfast approximately 30 minutes before dose administration. Subjects must consume the meal within 25 minutes or less. Washout period of 48 hours between dosing. |
| Name | Type | Description |
|---|---|---|
| Losmapimod oral tablet | DRUG | Losmapimod will be administered with food when possible. |
| Placebo oral tablet | DRUG | Placebo will be administered with food when possible |
| Losmapimod 15 mg oral tablet | DRUG | Subjects will receive one losmapimod 15 mg tablet by mouth under fasted conditions. |
| Losmapimod two 7.5 mg oral tablets | DRUG | Subjects will receive two losmapimod 7.5 mg tablets by mouth under fasted conditions. |
| Losmapimod one 15 mg oral tablet | DRUG | Subjects will receive one losmapimod 15 mg tablet by mouth under fed conditions. |
Inclusion Criteria: * The patient must have consented to participate and must have provided signed, dated and witnessed IRB-approved informed consent form that conforms to federal and institutional guidelines. * Male or female subjects * Confirmed diagnosis of FSHD1 with 1 to 9 repeats via assessme...
Losmapimod is an investigational small molecule being studied for the treatment of Facioscapulohumeral Muscular Dystrophy (FSHD), a genetic muscle disorder. It is currently in Phase 2 clinical development and has not been approved by the FDA. The drug has received Fast Track and Orphan Drug designations from the FDA.
Losmapimod is a small molecule that targets p38 mitogen-activated protein kinase (MAPK). By inhibiting this kinase, it is believed to reduce the expression of DUX4, a gene that is abnormally expressed in FSHD and leads to muscle damage. This mechanism is under investigation in clinical trials.
Losmapimod is being developed by Fulcrum Therapeutics, Inc., a biopharmaceutical company traded on NASDAQ under the ticker FULC. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with Facioscapulohumeral Muscular Dystrophy (FSHD).
Losmapimod is in Phase 2 clinical development for Facioscapulohumeral Muscular Dystrophy (FSHD). A Phase 2 trial has been completed, and the drug is not yet FDA approved. It has received Fast Track and Orphan Drug designations from the FDA, which may expedite its development and review.
Losmapimod has been studied in two completed trials. The main efficacy trial, NCT04003974, was a Phase 2, randomized, double-blind, placebo-controlled study in 80 patients with FSHD across the US, Canada, France, and Spain. A separate Phase 1 trial, NCT05002231, evaluated the drug's bioavailability and food effect in 18 healthy adults.
Losmapimod is also known by the code name GSK1995057. It was originally developed by GlaxoSmithKline and is now being developed by Fulcrum Therapeutics. The drug is being investigated for the treatment of Facioscapulohumeral Muscular Dystrophy (FSHD) and has completed Phase 2 trials.