ILB Safe, Shows Potential to Slow ALS Progression in Small Phase 2 Trial
TikoMed reported that ILB, its investigational therapy to protect nerve cells in amyotrophic lateral sclerosis (ALS), was well-tolerated by patients, and led to improvements in mobility and disease severity while reducing spasticity scores in a small open-label clinical trial.
“These early results from this ALS-study are exciting as ILB provided beneficial clinical effects without significant side effects,” Lennart Persson, MD, PhD, a professor at the University of Gothenburg in Sweden and the trial’s principal investigator, said in the company’s press release.
Results were detailed in the study “A phase II open label clinical study of the safety, tolerability and efficacy of ILB® for Amyotrophic Lateral Sclerosis,” published in PLOS One. The research was funded by Tikomed.
ILB, which contains a form of dextran sulphate, is believed to have multiple effects on the body that help prevent the dysfunction and death of nerve cells, which is characteristic of ALS. The investigational medication has been designated an orphan drug in the U.S. and Europe, supporting its development.
The Phase 2a trial (NCT03613571), conducted at Sahlgrenska University Hospital, enrolled 13 adults with ALS out of an initial planned recruitment of 15 people. All 13 were treated with five weekly under-the-skin injections of ILB at 1 mg/kg of weight, with additional monitoring for about 10 weeks afterwards.
Safety data were generally positive: over the course of the study, nine patients reported 14 side effects, and four of these (acne, bruising, fatigue, and fever) were judged potentially related to ILB treatment.
“These [adverse events] were of mild or moderate intensity and were all resolved without requiring any action related to” ILB, the researchers wrote.
No unusual laboratory measures were reported, and ILB’s pharmacological profile in these ALS patients was similar to findings from previous studies in people.
Blood analyses indicated that levels of hepatocyte growth factor (HGF), a signaling molecule that promotes nerve and muscle cell growth, rose by about 40 times within a few hours of each ILB injection and returned to around starting levels several hours later. Treatment with ILB also led to reductions in blood markers of muscle damage (myoglobin and creatinine kinase).
“The pharmacokinetics of ILB indicated rapid blood absorption of the drug after [subcutaneous] ILB injection, followed by fast clearance,” the researchers wrote.
Throughout the study, two standardized measures — the ALS Functional Rating Scale Revised (ALSFRS-R) and Norris rating — were used to assess disease severity. In both measures, higher scores indicate better functionality (i.e., less severe ALS).
Over the five-week treatment period, average ALSFRS-R scores increased by 2.5 points, while the average Norris rating increased by 7.3 points. Improvements in these scores were maintained for three to four weeks after the last dose of ILB before subsequently being lost.
By the end of dosing at trial day 36, none of the patients had experienced the amount of disease progression that would have been expected based on their clinical characteristics at the trial’s start. For most, this slowing of disease progression was sustained up to day 99 or about two months after the last dose.
“A measurable (using two widely adopted ALSFRS-R and Norris scoring systems) functional recovery emerged in this small patient cohort within one week of treatment initiation, that increased to statistical significance during the treatment period of five weekly ILB injections,” the researchers wrote.
“The alleviation of clinical symptoms lasted for 3–4 weeks after the last injection and was followed by a slow resumption of disease progression during the remaining 7 weeks of the follow-up period,” they added.
Scores for the severity of sensory and autonomic ALS symptoms (problems controlling subconscious bodily processes) also generally improved during the treatment period and were maintained for several weeks afterwards. Physical quality of life scores also improved significantly with ILB treatment.
Although the team stressed that this trial is limited by its small size and open-label design, they said these early data hint that ILB may have the potential to slow or even reverse ALS progression.
“Studies on ILB dosage and duration, inter-dosage intervals and possible long-term effects are in progress, but the present report supports ILB as the first safe, well tolerated treatment with potential to arrest/reverse the clinical symptoms of ALS,” the team concluded.
“As of yet, numerous trials have been unable to identify any agent that reverses or even halts the progressive symptoms of ALS which is why these clinical results with ILB, demonstrating both safety and tolerability whilst supporting the drug’s potential as a disease modifying treatment, are very promising,” said Anders Kristensson, CEO of TikoMed.
“Preclinical studies from our ILB program have also demonstrated the drug’s unique ability to enhance endogenous repair mechanisms and rebalance inflammatory responses providing a new, potentially invaluable mechanism of action in the treatment of neurodegenerative diseases,” Kristensson added.
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