Foralumab shows promise in nonactive SPMS, EAP data suggest

Tiziana Life Sciences‘ experimental nasal spray foralumab continues to show signs that it may help slow disability progression and ease fatigue in people with nonactive secondary progressive multiple sclerosis (SPMS), according to new data from an expanded access program (EAP).

Fourteen people with nonactive SPMS have been using the spray in the program (NCT06802328). After about three years of follow-up, one participant experienced a sustained worsening in disability scores.

While direct comparisons cannot be made, this rate appears lower than that observed in the Phase 3 HERCULES clinical trial (NCT04411641), in which another experimental therapy, tolebrutinib, significantly delayed disability progression in a similar population.

EAPs allow patients to use experimental therapies outside clinical trials.

“These longer-term results from the Expanded Access SPMS Program continue to support the potential of intranasal foralumab as a novel, immunomodulatory therapy for patients with non-active SPMS,” Howard L. Weiner, MD, chair of Tiziana’s scientific advisory board, said in a company press release.

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Easing fatigue

The data also continue to suggest that foralumab may help ease fatigue, one of the most common and debilitating symptoms of MS. In a standard assessment of fatigue severity called the Modified Fatigue Impact Scale (MFIS), nine of the 14 patients had clinically meaningful improvements of at least 4 points, while only two had clinically meaningful worsening.

Safety findings also remained consistent with prior reports. Tiziana said no new safety signals have emerged, and the therapy remains generally well tolerated.

“The excellent tolerability profile combined with trends toward disability stabilization and fatigue improvement is highly encouraging and warrants further investigation,” said Weiner, who is also director of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital in Boston.

MS is a chronic disorder marked by inflammation that damages healthy cells in the nervous system. In most people, the disease initially manifests as relapsing-remitting MS (RRMS), which is defined by relapses where symptoms suddenly worsen and periods of remission where symptoms ease. Over time, people with RRMS may progress to SPMS, which is defined by gradual disability worsening independent of relapse activity.

Some people with SPMS continue to experience occasional relapses and/or show signs of disease activity on MRI scans. These patients have what’s known as active SPMS, and treatments used for RRMS are generally also effective for this for of the disease. But available treatments are extremely limited for people with nonactive SPMS.

Foralumab is an antibody-based therapy that targets CD3, a protein produced by T-cells, a type of immune cell. The therapy aims to modulate the activity of T-cells and other immune cells to dampen MS-driving inflammation.

“Intranasal foralumab’s unique mechanism, which reduces neuroinflammation, positions it as a potential new treatment paradigm for progressive forms of multiple sclerosis where treatment options remain limited,” said Ivor Elrifi, CEO of Tiziana. “We look forward to advancing this program to approval.”

Tiziana is sponsoring a Phase 2a clinical trial (NCT06292923) that aims to test foralumab against a placebo in about 54 adults with nonactive SPMS who have experienced disability worsening despite at least two years of treatment with available MS treatments.

The main goal is to assess the safety of the experimental therapy, its effect on nasal symptoms, and changes in the activity of brain immune cells called microglia. Researchers are examining changes in disability progression and fatigue as secondary endpoints.