Tiziana Announces Planned Phase 2 Study of Foralumab in Progressive Multiple Sclerosis

Gabriele Cerrone

Following positive feedback from a type C meeting with the FDA, Tiziana Life Sciences announced that the company plans to start a phase 2 study later this year to assess its investigational anti-CD3 monoclonal antibody foralumab in patients with non-active secondary progressive multiple sclerosis (MS).

The company is expected to accept the FDA’s recommendations, with protocol for the trial to be submitted in April. Foralumab, which is currently being studied in Crohn’s and other neurodegenerative diseases, is designed to bind to the T cell receptor and dampens inflammation by modulating T cell function, thereby suppressing effector features in multiple immune cell subsets.

"Tiziana has reached an important regulatory milestone as it proceeds with the first ever intranasal foralumab clinical trial," Gabriele Cerrone, executive chairman and interim chief executive officer, Tiziana Life Sciences, said in a statement. "The FDA’s response to our proposed Phase 2 program allows Tiziana’s to advance foralumab through the regulatory process as we strive to bring this novel treatment to patients with non-active SPMS."

Currently, 6 patients with secondary progressive MS are being treated at Brigham and Women’s Hospital in Boston, Massachusetts, with intranasal foralumab under expanded access investigational new drug applications (IND) with signs of clinical benefit. At the 2023 Consortium of Multiple Sclerosis Centers (CMSC) annual meeting, Tanuja Chitnis, MD, presented data on one of these patients, a 61-year-old male who had non-active secondary progressive MS for over 20 years.²

The individual entered the study with noticeable disease progression despite treatment with ocrelizumab (Ocrevus; Genentech), an FDA-approved anti-CD20 agent. Treatment with foralumab was initiated in May 2021 and was continued for 6 months with a 7-week washout period after 3 months. In addition to showing a safe treatment profile, treatment with foralumab resulted in clinical symptom progression subsiding. Microglial activation, as measured by F-18 PBR06 PET scan, was significantly reduced 3 months after the start of treatment, with reductions sustained after the 7-week washout and at 6 months. Notably, pro-inflammatory cytokines IL-1ß and IL-6 were reduced, as well as Th1 cytokines IFN-y and IL-18.

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In addition to MS, the company has plans to assess foralumab in Alzheimer disease. The company is expected to file an IND by the third quarter of 2023 upon the completion of requested toxicology studies, with the phase 1 program beginning by the end of the year. The decision came after the company received an affirmative response from the FDA on a pre-investigational new drug application.

"I am grateful for the FDA’s thoughtful review of our Phase 2 plans for intranasal foralumab," Matthew W. Davis, MD, RPh, chief medical officer, Tiziana Life Sciences, said in a statement. "This upcoming quarter, we will update the Phase 2 protocol with the FDA’s suggestions and plan to start the Phase 2 clinical trial by holding our first investigator’s meeting in Q3 2023."

Foralumab has also been assessed in patients with mild to moderate COVID-19. Published in August 2021, the study featured 39 outpatients who were randomized to either control (n = 16), intranasal foralumab 100 µg/day given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n = 11), and intranasal foralumab 100 µg/day along given for 10 consecutive days (n = 12). All told, investigators observed a reduction of serum interleukin-6 and C-reactive protein in patients treated solely with foralumab vs controls or those on a combination approach. Specifically, foralumab alone resulted in a 69% reduction in IL-6 levels at day 10 (P = .031) and 85% reduction in CRP at day 10 (P = .032).

REFERENCES
1. Tiziana Life Sciences to proceed with phase 2 clinical trial in patients with non-active secondary progressive multiple sclerosis (SPMS). News release. March 28, 2023. Accessed March 28, 2023. https://www.globenewswire.com/news-release/2023/03/28/2635516/0/en/Tiziana-Life-Sciences-to-Proceed-with-Phase-2-Clinical-Trial-in-Patients-with-Non-Active-Secondary-Progressive-Multiple-Sclerosis-SPMS.html
2. Chitnis T, Singhal T, Zurawski J, et al. Nasal anti-CD3 monoclonal antibody (foralumab) reduces PET microglial activation and blood inflammatory biomarkers in a patient with non-active secondary progressive MS. Presented at: CMSC Annual Meeting, 2022; June 1-4; National Harbor, MD. LB
3. Moreia TG, Matos KT, De Paula G, et al. Nasal administration of anti-CD3 monoclonal antibody (foralumab) reduces lung inflammation and blood inflammatory biomarkers in mild to moderate COVID-19 patients: a pilot study. Front Immunol. Pubished online August 12, 2021. doi:10.3389/fimmu.2021.709861