Tiziana Planning 2023 Launch of Phase 2 Foralumab Trial in SPMS

Tiziana Life Sciences plans to request a meeting with the U.S. Food and Drug Administration (FDA) later this year to discuss the upcoming Phase 2 clinical trial of foralumab nasal spray in people with nonactive secondary progressive multiple sclerosis (SPMS).

FDA feedback on the design of the multicenter, placebo-controlled trial is expected in the first months of 2023. Should it be positive, the proof-of-concept trial will launch in the second quarter of the year, Tiziana reported in a recent corporate update.

Updated results from the ongoing expanded access programs, evaluating foralumab in SPMS patients at Brigham and Women’s Hospital in Boston, are also expected early in 2023, with four additional patients to be enrolled in the second half of the year.

The company is meanwhile moving forward with the development of foralumab in other inflammatory diseases of the central nervous system (CNS), or those involving the brain and spinal cord, including amyotrophic lateral sclerosis and Alzheimer’s disease.

Recommended Reading

November 2, 2022 News by Lindsey Shapiro, PhD

#ECTRIMS2022 – DMTs Ease SPMS Disability Early but Not Over Time

“We look forward to leveraging the exciting clinical and preclinical results from our very promising formulation of intranasal foralumab that we have generated so far in CNS-based autoimmune diseases to guide our pipeline investment,” Gabriele Cerrone, executive chairman and interim CEO of Tiziana, said in a company press release.

“We aim to become a leading company pioneering intranasal therapies for CNS-based diseases,” Cerrone added.

Foralumab’s design and testing

Foralumab is an antibody-based treatment designed to reduce inflammation by targeting the CD3 protein found on the surface of T-cells, a type of immune cell implicated in the inflammatory attacks that drive MS and other neurodegenerative diseases.

Preclinical studies have demonstrated that, when delivered into the nose, foralumab is taken up in the lymph nodes, where it activates regulatory T-cells. These cells act to regulate the activation of other immune cells, then travel into the brain, where they work to prevent activation of microglia — the brain’s resident immune cells — and dampen inflammation.

Tiziana believes foralumab shows significant promise for treating patients with nonactive SPMS, which is marked by continuous disability progression in the absence of relapses, for which treatment options are lacking.

Foralumab is now being evaluated in nonactive SPMS patients under two single-patient access programs and an expanded access program that has enrolled an additional four patients.

The two patients treated in the single-access programs are receiving a 50 microgram (mcg) dose of foralumab into each nostril in three-week cycles — three doses per week for two weeks, followed by a week of rest.

Both patients, who were experiencing disease progression despite treatment before starting foralumab, saw improvements in cognitive and walking function that have been sustained for at least six months.

Clinical gains were accompanied by a suppression of microglial activation in the brain, as observed on PET scans. Microglia are thought to be significant drivers of inflammation in MS and other neurodegenerative diseases.

Results from additional PET scans — after nine months of treatment in the first patient and six months in the second — are expected in the first quarter of 2023.

Based on positive findings from these two patients, the FDA subsequently cleared a special access program that would allow foralumab to be tested in up to eight more patients.

That program recently enrolled four people who will also be treated at the 50 mcg dose. If needed, the dose can be increased to 100 mcg in the second group of patients.

Dosing is expected to begin by the end of this year, and three-month PET scans will be completed in the first part of 2023, with results expected in the months following.

As the development of foralumab for SPMS and other CNS diseases progresses, the company says it will de-prioritize development of some other foralumab formulations for non-CNS conditions.

“Tiziana along with our academic partners collectively believe that many inflammatory CNS disease pathologies could benefit from intranasally administered foralumab and, as such, are focusing our efforts in this area,” said Matthew W. Davis, MD, chief medical officer of Tiziana.