Dosing begins in Phase 2a trial of foralumab nasal spray for SPMS

Early data on therapy’s effects on brain immune cells expected by end of 2024

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Tiziana Life Sciences has dosed the first patient in a Phase 2a clinical trial testing its foralumab nasal spray in people with nonactive secondary progressive multiple sclerosis (SPMS).

The trial will include about 54 participants, enrolled across six clinical sites. Patients will be randomly assigned to receive one of two doses of foralumab or a placebo, and neither investigators nor patients will know which treatment they are receiving. Early data is expected by the end of 2024.

“I am very pleased the first patient has been dosed and our team is committed to remaining on track with our milestones. We are poised to accelerate enrollment and anticipate data readout in Q4 [fourth-quarter] 2024,” Matthew W. Davis, MD, Tiziana‘s chief operating officer and chief medical officer, said in a company press release.

The trial’s main goal is to assess changes in the activity of microglia — brain resident immune cells known to contribute to multiple sclerosis (MS) progression — using positron emission tomography (PET) imaging scans.

In addition, researchers will monitor changes in several clinical parameters, including disability progression — as assessed with the Expanded Disability Status Scale (EDSS) — quality of life, and fatigue. Levels of novel inflammatory biomarkers also will be measured to assess their ability to predict responses to treatment.

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Tiziana also testing foralumab in expanded access programs

“The successful consenting, screening, completion of the baseline PET scan, and dosing of our first patient in the intranasal foralumab Phase 2a trial has occurred seamlessly,” said Tanuja Chitnis, MD, a principal investigator at the Brigham and Women’s Hospital, in Boston.

The Brigham and Women’s Hospital has been running foralumab’s expanded access programs (EAPs), under which nonactive SPMS patients with no alternative therapies could have access to the experimental treatment.

To date, a total of 10 nonactive SPMS patients have enrolled in these EAPs. Two patients are receiving foralumab as part of single-patient access programs, and the remaining eight are being treated in an intermediate-size EAP.

The treatment is administered at a 50 microgram (mcg) dose, sprayed into each nostril in cycles of three weeks — three times weekly for two weeks, followed by a week of pause.

Data from the first six EAP participants who received foralumab for at least six months indicated that the treatment is safe and well tolerated, and that it reduced microglia activity in five patients.

Two participants also experienced a reduction in their EDSS scores, indicating an easing in disability levels, while disability remained stable in the other four patients.

The Phase 2a trial “is the first step in bringing this potential treatment to patients that have [nonactive] SPMS, a disease with no approved therapy,” according to Chitnis.

“Our experience in the Expanded Access Program provides sustainable hope for relief of symptoms in these patients with an unmet medical need,” Chitnis added.

[The Phase 2a trial] is the first step in bringing this potential treatment to patients that have [nonactive] SPMS, a disease with no approved therapy.

Nonactive SPMS is a form of multiple sclerosis that follows relapsing-remitting MS, in which patients experience a steady worsening of symptoms in the absence of relapses or new MRI activity. This form of the disease has a high unmet need for treatments, as mitoxantrone is the only therapy approved to date for these patients.

Foralumab is an antibody-based therapy. It’s designed to ease inflammation in MS by targeting the CD3 protein receptor that’s found at the surface of immune T-cells, which are known to play an important role in driving immune-related damage in MS.

By blocking CD3, the therapy is expected to hamper the activity of damaging T-cells, while boosting the activation of regulatory T-cells that prevent excessive immune reactions.

While oral and infusion formulations of CD3 inhibitors have been shown to cause unwanted adverse events, the nasal administration of foralumab enables a more localized action and the use of much lower doses compared with the other formulations. This is expected to improve the treatment’s safety, tolerability, and efficacy, according to Tiziana.

“Our dosing of the first patient confirms Tiziana’s … potential to advance our fully human intranasal anti-CD3 [antibody] foralumab, using novel imaging methods and clinically relevant endpoints” said Gabriele Cerrone, chairman, acting CEO, and founder of Tiziana.

“We hope our efforts will give a new therapeutic option to patients afflicted with this devastating disease,” Cerrone said.