ILB may slow ALS progression, per data from small clinical trial
Injection therapy shows good safety and potential long-term efficacy
Treatment with a high dose of ILB, an experimental injection therapy being developed by Tikomed, was well tolerated and appeared to slow the progression of amyotrophic lateral sclerosis (ALS) in a small clinical trial in the U.K.
That’s according to data from the exploratory Phase 2 study (NCT03705390), in which the therapy was tested in 11 adults with the progressive neurodegenerative disease.
The results were detailed in “A low molecular weight dextran sulphate, ILB, for the treatment of amyotrophic lateral sclerosis (ALS): An open-label, single-arm, single-centre, phase II trial,” a study published in the journal PLOS One.
“This trial represents another significant milestone for the company, and I am very impressed and grateful that the trial results are now peer-reviewed and published,” Lars Bruce, one of the founders of Tikomed, said in a company press release.
Ann Logan, scientific advisor to Tikomed and a professor at the University of Warwick, in England, added that the findings “indicate the future potential of ILB to be the first disease-modifying drug to treat both familial and sporadic ALS with minimal side effects.”
No changes in ALS rating scores indicate slowing of disease progression
ILB, a formulation of the sugar molecule dextran sulfate, is thought to promote nerve health by prompting the release of signaling molecules that encourage nerve survival.
The experimental medication, which is administered subcutaneously, or via under-the-skin injections, is being explored to slow the nerve cell degeneration that drives ALS. It has been named an orphan drug in the U.S. and Europe as a potential ALS treatment.
An earlier Phase 2 study (NCT03613571), conducted in Sweden, explored the therapy’s use in 13 ALS patients. Each received five weekly subcutaneous injections of ILB at a dose of 1 mg per kilogram of body weight (mg/kg). Results after about 15 weeks, or slightly longer than three months, showed the treatment was generally safe and hinted that it could slow or even reverse disease progression.
Based on this data, scientists conducted a follow-up Phase 2 study with a similar design, but testing a higher weekly dose of 2 mg/kg for at least 10 weeks, or just longer than two months. Some patients received treatment for up to 48 weeks, or nearly one year.
While the trial originally planned to recruit 15 patients, it was terminated early in 2020 due to the COVID-19 pandemic; at that point, a total of 11 patients had been enrolled. Still, researchers evaluated the available data to see what could be learned.
Mirroring earlier findings from the low-dose trial, ILB was, overall, well tolerated at the higher dose, with no serious side effects related to treatment. The most common side effect of ILB was mild bruising. There also were a few instances of abnormal lab tests such as increased liver damage markers, but none were serious.
The delivery of fast functional benefit alongside long-term disease [stabilization] would make ILB a unique treatment option for this devastating disease.
Throughout the study, patients were assessed with the Revised ALS Functional Rating Scale (ALSFRS-R) and the ALS Assessment Questionnaire (ALSAQ-40). The ALSFRS-R is a measure of functionality commonly used to track the progression of ALS symptoms, while the ALSAQ-40 is a disease-specific measurement of life quality.
Available data showed that both ALSFRS-R and ALSAQ-40 scores were largely stable over the course of treatment. By the end of follow-up, there were no clinically significant changes on any of these measures.
As ALS is a progressive disease in which symptoms tend to get continuously worse over time, these data imply that ILB may have helped slow the progression of the disease. The researchers cautioned, however, that because this was a small study that did not include a placebo group for comparison, “definitive conclusions regarding these data cannot be drawn.”
Still, Logan said that these data in combination with findings from the earlier study using a lower dose of ILB “demonstrate the safety and tolerability of ILB in patients with ALS and further suggest a long-term slowing of disease progression in addition to the already reported rapid improvements in patient biochemistry and residual motor function.”
“The delivery of fast functional benefit alongside long-term disease [stabilization] would make ILB a unique treatment option for this devastating disease,” Logan said.
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