8 More SPMS Patients Cleared for Foralumab Nasal Spray Treatment
Based on findings from the first two secondary progressive multiple sclerosis (SPMS) patients given foralumab nasal spray, an experimental therapy, the U.S. Food and Drug Administration (FDA) has approved starting treatment in up to eight other patients under a special access program.
Those enrolled in this intermediate-size expanded access program — anticipated to start in July — will receive the immunomodulatory therapy at Harvard Medical School’s Brigham and Women’s Hospital (BWH), similar to the first two patients treated in ongoing single-patient access programs.
“Therapies to slow progression in multiple sclerosis are much needed,” Tanuja Chitnis, MD, the study’s principal investigator, a neurology professor at BWH, and a member of the scientific advisory board of Tiziana Life Sciences, the therapy’s developer, said in a press release.
Foralumab nasal spray comprises “a novel physiological approach to … induce disease-modifying benefits in the CNS [central nervous system; the brain and spinal cord] by dampening microglial inflammation,” said Howard Weiner, MD, director of the Multiple Sclerosis Program at BWH and chairman of Tiziana’s scientific advisory board.
Microglial cells — the CNS’ own immune cells — have been implicated in the abnormal inflammatory and immune responses that drive neurodegeneration in multiple sclerosis (MS).
“The first validation of our innovative approach came from our recently reported results showing positive clinical benefits and microglial modulation in a patient with secondary progressive multiple sclerosis who was treated for six months with nasal foralumab,” Weiner added.
The first single-patient program was approved by the FDA in April 2021, and the second in January. With the agency’s permission, the first patient is continuing treatment for another six months to determine whether the observed benefits can be sustained. Findings after three months of treatment for the second patient are expected in May.
“We are grateful to have the opportunity to offer intranasal foralumab to progressive MS patients,” Chitnis said.
The new access program is expected to provide additional data to assess the robustness of clinical responses to treatment. Its main goals are to determine foralumab’s safety and tolerability, while additional goals include clinical and immune responses.
The intermediate-size program will follow the same dosing regimen as the two single-patient programs: 50 micrograms of foralumab into each nostril in three-week cycles — three doses each week for two weeks, followed by one week of rest.
If needed, newly enrolled patients may receive higher doses, up to 100 micrograms three times a week, to improve clinical benefit.
Notably, the first patient given foralumab was experiencing continuous disease worsening, with a clear decline in walking abilities over the previous two years. Several MS therapies, including those suppressing immune cells known to contribute to MS, had failed to help.
According to previously reported data, six months of treatment with foralumab nasal spray were generally well-tolerated and resulted in improvements in the patient’s walking ability, finger dexterity, and cognitive function.
These benefits were accompanied by a gradual reduction in microglial cell activation — up to 50% at six months — throughout the brain, as assessed with positron emission tomography (PET) scans.
Microglial cell activation has been reported to be abnormally high in SPMS patients and associated with greater disability. It is also associated with other neurodegenerative diseases linked to chronic brain inflammation, such as Parkinson’s, and Alzheimer’s.
In animal studies, several FDA-approved MS therapies, including Tysabri (natalizumab), Mayzent (siponimod), and Zeposia (ozanimod), were shown to suppress microglial activation and promote neuroprotective effects in the CNS. However, their microglia-related effects in SPMS patients over time are still unclear.
Foralumab data now provide, for the first time, strong evidence of a link between lesser microglial activation and clinical gains in SPMS patients.
“This now opens the door to treat other neurologic diseases which have microglial inflammation — such as Alzheimer’s disease — with intranasal foralumab,” Weiner said.
Foralumab is an antibody designed to suppress inflammatory and immune responses by targeting the CD3 receptor protein on the surface of T-cells, a type of immune cell involved in the abnormal immune attacks that drive nerve cell death in MS.
Notably, the therapy was previously found to not only reduce the activity of inflammatory T-cells, but also to increase that of regulatory T-cells, which work by dampening the inflammatory activity of other immune cells.
Administered directly into the nostrils, foralumab nasal spray is expected to act more locally so to have a more favorable safety profile than conventional antibody-based treatments, which are administered into the bloodstream.
In a previous Phase 1 clinical trial, the nasal spray was found to be generally safe and well-tolerated in healthy volunteers. The therapy also led to a reduction in T-cell subsets and inflammatory molecules, and an increase in the levels of anti-inflammatory molecules.
Tiziana announced in January that it anticipates opening a Phase 2 trial of nasal foralumab in people with progressive forms of MS.