by Danielle Bradshaw from In The Cloud Copy
Fulcrum Therapeutics, a company that focuses on clinical-stage biopharmaceuticals to improve the quality of life for patients that have rare genetic diseases, announced the primary endpoint results of the Phase 2 ReDUX4 trial with participating patients that have facioscapulohumeral muscular dystrophy (FSHD).
The primary endpoint – or end-exam-results – was a decline in the baseline of DUX4-driven gene expressions (gene expression is the process that information inside of genes uses to create protein molecules) in negatively impacted skeletal muscles after the patients have been given either losmapimod or a placebo.
What is Facioscapulohumeral Muscular Dystrophy?
FSHD is a rare variation of muscular dystrophy that primarily targets (weakens) the face’s skeletal muscles. The disease also attacks the muscles that keep the scapula in place, those located in the upper part of the arm on top of the humerus bone.
This skeletal muscular weakness can also happen in the abdomen and near the shin as well. Patients with this illness can also manifest non-muscular issues such as blood vessel problems in the back of their eyes and loss of hearing.
FSHD symptoms most often develop in one half of the body sooner than the other and are more likely to occur during early childhood; the effects become more pronounced during a person’s teenage years. This disease is progressive and approximately 95% of all FSHD patients will have begun showing signs of the disease by the time they reach 20-years-old.
Malfunctions inside the DUX4 gene is what causes FSHD. To be more specific, genetic changes that occur involve a person’s DUX4 protein being improperly “switched off”. In this case, the DUX4 protein results in the patient’s muscles dying and being replaced by fat.
What Was the ReDUX4 Trial?
ReDUX4 was a double-blind, randomized trial. The proceedings used a placebo control and was an international Phase 2b clinical trial that involved 80 FSHD patients taking losmapimod or placebo orally to test both its safety and effectiveness.
The reduction of DUX4 gene expression is then evaluated by observing biopsies taken from skeletal muscles affected by FSHD. Because of the ongoing pandemic, however, Fulcrum changed the original design of the trial. It was extended from 24 to 48 weeks to make sure that the participants made it through the trial safely. With the trial’s original design, a muscle biopsy would have taken place around 16 weeks into the 24-week treatment period which would have then been followed up with an open-label extension.
The Trial’s Interim Analysis Summary
The ReDUX4 trial didn’t involve either a secondary or exploratory endpoint assessment. The interim analysis involved a study of 29 of the 80 participants who’d already received their biopsies. There were assessments done on the pharmacokinetics of the drug (how the drug is absorbed, distributed through the body, and excreted), demographics, and the primary endpoint.
15 of the participants were given 15mg of the drug and 14 of them a placebo twice per day. The results demonstrated a large decrease in DUX4-driven gene expression in muscle biopsies of the patients with a baseline that has the largest levels of DUX4 gene expression.
Here, there was a 38-fold (meaning a ridge formed by the creasing of the membrane) decline in three patients using losmapimod while five of them saw a decrease with the placebo. All 29 participants showed no separation of the losmapimod from the placebo with a 3.7-fold increase in 15 of the participants taking losmapimod and a 2.8-fold increase in the 14 taking the placebo.
The overall results seem to indicate that losmapimod had no negative drug-related effects and that the patients were able to tolerate it well. In addition, it may have some limited benefit for treating the disease.
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