Foralumab shows promise in early study of nonactive SPMS
Data show treatment eased fatigue, disability in some patients
Foralumab was well tolerated in people with nonactive secondary progressive multiple sclerosis (SPMS), according to data from a small, open-label study conducted under an expanded access program.
The therapy, being developed by Tiziana Life Sciences, also eased fatigue and lessened disability in some participants. The promising findings formed the basis for a Phase 2a study (NCT06292923) that’s currently testing foralumab against a placebo in adults with nonactive SPMS. The trial is still recruiting at sites in the U.S.
“We are incredibly excited by these results, which validate the potential of nasal foralumab to fundamentally shift the treatment paradigm for progressive MS,” Ivor Elrifi, PhD, CEO of Tiziana, said in a company press release.
Most people with multiple sclerosis (MS) initially develop relapsing-remitting disease (RRMS), which is marked by flares when symptoms worsen, interspersed with periods of remission when symptoms ease. Over time, people with RRMS can progress to SPMS, in which symptoms gradually worsen over time independent of relapse activity.
Some people with SPMS continue to experience flares (known as active SPMS), but those with nonactive SPMS do not see flares or other signs of disease activity in MRI scans.
Limited treatment options for nonactive SPMS
Treatment options for nonactive SPMS are limited. While there are more than 20 treatments available for relapsing MS types, only one medicine, mitoxantrone, is authorized in the U.S. to treat nonactive SPMS.
“Our findings mark a significant advancement for patients living with non-active Secondary Progressive MS, who currently have very limited treatment options,” said Tanuja Chitnis, MD, principal investigator of the open-label study and a neurology professor at Harvard Medical School.
Foralumab is designed to treat MS by reducing the activity of T-cells, a type of immune cell that plays a central role in the inflammatory attack on the nervous system that drives MS. It also boosts the activity of certain immunosuppressive T-cells called Tregs, which can dampen the inflammatory function of other immune cells.
The therapy is administered as a nasal spray three times a week, following a two-week on, one-week off schedule.
“Nasal administration of foralumab represents a novel, non-invasive approach that not only induces regulatory immunity but also reduces harmful [inflammation in the brain and spinal cord,” Chitnis said.
In the open-label trial, 10 people with nonactive SPMS whose disease continued to progress despite being on anti-CD20 therapies were treated with foralumab for at least six months. The patients were treated at the Brigham and Women’s Hospital in Boston as part of an expanded access program.
Findings ‘support more studies,’ researchers say
Results from the study were made available in the preprint, “Nasal foralumab treatment of PIRA induces regulatory immunity, dampens microglial activation and stabilizes clinical progression in non-active secondary progressive MS.” The paper has not yet undergone peer review, the process in which other scientists review the data for technical issues.
Results showed that foralumab was well tolerated, with no serious safety issues related to the therapy reported in the trial. Most of the side effects reported were respiratory issues like nasal congestion or runny nose.
After six months on therapy, scores on the Expanded Disability Status Scale (EDSS), a standard measure used to track disability in people with MS, were unchanged for almost all of the participants. The only exceptions were three patients who experienced slight reductions in EDSS scores, suggesting less severe disability.
Four participants were continuously treated with foralumab for a full year. Three of them experienced a reduction in EDSS scores after a year on the therapy.
“After starting nasal foralumab, the EDSS score stabilized in all patients, and none worsened over the six-month period, with some patients experiencing an improvement in EDSS after longer-term treatment,” the scientists wrote.
Another measure of disability that combines assessments of walking function, dexterity, cognition, and vision problems showed no changes in walking or hand function over the six months, and significant improvements in vision. There were also slight improvements in cognitive scores, “likely due to practice effect,” the researchers said.
Fatigue is a common and disabling symptom of MS. After six months of treatment with foralumab, six of the 10 participants reported clinically significant reductions in fatigue severity.
Biomarker data from the study indicated that foralumab treatment reduced inflammation in the nervous system as designed. It dampened the activity of microglia in the brain, which is believed to be a main contributor to the silent disease progression experienced by people with nonactive MS.
Although the findings are promising, the researchers stressed that this was a small, open-label study without a placebo comparator, so it’s not possible to rule out the placebo effect in any of the results. They said the findings “support further studies to evaluate the effects of nasal [foralumab] in progressive forms of MS.”
The open-label study was funded by the Water Cove Charitable Foundation and the Ann Romney Center for Neurologic Diseases, with foralumab provided by Tiziana.
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