In this video, Diego Cadavid, MD, Senior Vice President, Clinical Development, at Fulcrum Therapeutics provides an update on ReDUX4, the Phase 2b clinical trial currently underway testing the safety and efficacy of losmapimod to treat facioscapulohumeral muscular dystrophy (FSHD).
The company started recruiting volunteers for the trial in August of 2019 and completed enrollment in February of this year. The trial involves 80 patients across 17 sites in 4 countries including U.S. Patients were randomly allocated to take placebo or losmapimod. The study is going well, with some changes to accommodate the COVID-19 pandemic. The trial was amended to last 48 weeks, and interim results are expected in the third quarter of 2020 on an initial group of patients. Final results will be gathered in the first quarter of 2021. By then the trial will have all the data on biomarkers and exploratory clinical endpoints. “These are very important,” he says, “because ultimately you want to show that patients are benefitting in activities of daily life,” such as the movement of shoulders, ability to get up from a bed or chair, or walk around the house.
Fulcrum has been working with collaborators to develop trial endpoints on the use of shoulders and arms, or “reachable workspace,” and on a measurement called “timed up and go.” The standard test measures the time for a person seated in a chair to stand up and walk across a room, but Fulcrum modified the test for FSHD because patients reported having difficulty getting up not just from a chair but from lying down in a bed. The modified test is “working” and “very reliable,” says Cadavid. He notes that Fulcrum is working with a company called Emerald that uses touchless sensors in volunteers’ homes. “We were able to measure the activity of 10 patients at home and compared them to measurements taken in the clinic,” he said. The remotely collected data had “high correlations” with clinic data. “So this provides very important validation. We’ve shown that what we measure in the clinic actually represents what’s happening in the real world,” he says.
“The patients have been wonderful, everyone is working hard so we can answer the key question: is losmapimod treating the root cause, and are we beginning to see benefits?”
“because ultimately you want to show that patients are benefiting in activities of daily life, such as the movement of shoulders, ability to get up from a bed or chair, or walk around the house.”
That’s a strong statement on a hopeful losmapimod trial outcome presented from a very respectable source and would be remarkable, if achieved.
The statement indicates expectations not just at slowing or stopping FSHD progression, but disease reversal to some degree.
I would guess seeing such a remarkable outcome, including disease reversal, would be highly dependent on the state of disease progression in the specific muscle being tested on a specific patient.
Granted, showing disease halting or slowing is difficult to show in a 48 week study, but shouldn’t such a limited end result be sufficient for success, if achieved? I expect this might only be proven successful via biomarker studies and then we have to trust the science that DUX4 is the correct target, shoot for FDA conditional approval and then watch the results in clinic over 5-10 years.
Not meaning to sound negative… disease reversal would be fantastic! I just want to understand what trial endpoints define success for losmapimod. Thanks!