Nasal Foralumab Led to Promising Immune Effects in Phase 1 Trial

Nasally-administered foralumab, a potential treatment for neurodegenerative disorders such as progressive forms of multiple sclerosis (MS), appears safe and well-tolerated, and shows immune-modulating and anti-inflammatory effects in healthy volunteers, an updated analysis from a Phase 1 trial has found.

“Nasal administration of Foralumab is a unique approach to treat patients with neurodegenerative diseases such as progressive MS, amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease,” Howard Weiner, MD, the Harvard Medical School neurology professor who reformulated foralumab for nasal delivery, said in a press release.

Foralumab, developed by Tiziana Life Sciences, is an experimental antibody targeting the CD3 receptor on immune T-cells. This lessens T-cells’ potentially damaging immune responses, while increasing the activity of separate regulatory T-cells that work to prevent inappropriate immune reactions.

Both the oral and nasal routes of administration are designed to stimulate the immune system associated with mucus membranes to provide a disease-modifying effect, said Weiner, who is also chair of the scientific advisory board at Tiziana.

The treatment’s safety and preliminary signs of effectiveness are being investigated in a group of healthy volunteers participating in a Phase 1 trial at the Brigham and Women’s Hospital, Harvard Medical School, in Boston.

Participants received ascending doses of 10, 50, and 250 micrograms of foralumab, or a placebo, once daily for five consecutive days.

Results showed that all doses were well-tolerated, with no signs of severe toxicity or of a potentially life-threatening condition called cytokine release syndrome.

Nasally-administered foralumab appeared to work on the local immune system near its administration site and on the lymphatic immune system, as it was not found in any significant quantity elsewhere in the body.

The 50-microgram dose had the greatest effect on immune T-cells, which can turn on the body’s own tissue in autoimmune disorders such as MS.

This dose of foralumab had three statistically significant effects: it reduced T-cell subsets over 14- and 21-day periods, increased CD8-naïve T-cells, and boosted production of the anti-inflammatory molecule IL-10 while suppressing the inflammatory molecule interferon gamma.

“This study demonstrates for the first-time that nasally administered Foralumab, at the identified optimal dose of 50 mcg [micrograms]/day, induces immunomodulatory effects capable of providing clinical benefit to treated subjects,” Weiner said.

These immune-modulating and anti-inflammatory effects, the company wrote, are consistent with observations from a trial in Brazil, in which nasal foralumab was administered to COVID-19 patients.

“These data, along with results from our recently completed trial in COVID-19 patients in Brazil suggest a dose-range of 50 mcg-150 mcg could be used for future clinical development of nasally administered Foralumab,” added Weiner.

“Our immediate focus,” he said, “is on developing foralumab for treatment of progressive MS.”

Tiziana recently treated, for the first time, a person with secondary progressive multiple sclerosis with foralumab in an individual patient expanded access program. The patient will be receiving the 50-microgram dose in three-week cycles — consisting of three doses per week in the first two weeks followed by a week off treatment — for six months.