Intranasal Foralumab for Multiple Sclerosis Now Approved by FDA for At-Home Dosing

This was originally published in NeurologyLive.

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The FDA has allowed Tiziana Life Sciences’ agent foralumab, a fully human intranasal anti-CD3 monoclonal antibody, to be taken at home and self-administered for the treatment of patients living with multiple sclerosis (MS). The company noted that this decision by the FDA to allow patients to self-administer this therapy at home is a significant advancement in the landscape of care in MS, increasing accessibility and allowing for more convenience for patients with this condition.

Foralumab is designed to bind to T cell receptor and dampens inflammation by modulating T cell function, thereby suppressing effector features in multiple immune cell subsets. The agent is administered intranasally, providing a novel avenue for the treatment of inflammatory human diseases. Tiziana also noted they developed delivery device training materials and refined them in collaboration with the agency. Therefore, patients with MS will be trained in the use of the nasal device in accordance with the instructed materials.

“Traditionally, patients with MS had to visit healthcare facilities for treatment, which could be inconvenient and burdensome. The FDA's approval for home dosing of foralumab will transform the way patients manage their condition, offering them greater control over their treatment schedules and the convenience of receiving care in their familiar environment,” Gabriele Cerrone, executive chairman and interim chief executive officer at Tiziana Life Sciences, said in a statement.1 "We are elated with the FDA's allowance for home dosing of intranasal foralumab. This step significantly aligns with our mission to make innovative therapies more accessible to patients and ultimately improve their quality of life. We believe that this treatment approach will revolutionize the way patients with MS manage their condition."

At MSMilan 2023, the joint ECTRIMS-ACTRIMS meeting, held October 11-13, in Milan, Italy, a small-scale study of patients with non-active secondary progressive multiple sclerosis (SPMS) treated with foralumab showed improvements in clinical measures of fatigue and physical function. All patients with SPMS in the study (n = 6) experienced improvement in at least 1 clinical measure of Expanded Disability Status Scale (EDSS), pyramidal score, or Modified Fatigue Impact Score (MFIS), and all but 1 (5 of 6) showed improvement on microglial PET imaging at 6 months.

Using 18F-PBR06-microglial PET imaging, results showed that 5 of the 6 participants had reductions in PET signal at 3- and 6-months after initiating treatment. Notably, no new T2 or gadolinium-enhancing lesions were noted on post-treatment 3T MRIs. The therapy was shown to be safe and well tolerated with runny nose and nasal congestion, both self-limited, as the only treatment-related adverse events (AEs). Two patients had serious AEs deemed unrelated to the study drug (Patient EA1 and EA2 – COVID diagnosis; EA1 – 2 episodes UTI/cystitis associated with benign prostatic hyperplasia).

“Since the beginning of the na-SPMS EA program, patients have been going to the MS clinic at Mass General Brigham to receive their 3-times a week dosing. Now, these patients will only need to go to the clinic once every 3 weeks. This dosing and medical evaluation schedule will also be mirrored in our phase 2a double-blind study, which is to start in November,” William A. Clementi, PharmaD, FCP, chief development officer at Tiziana said in a statement.

Tiziana is still planning to start a phase 2 study later this year assessing the efficacy and safety of foralumab among patients with SPMS. The trial’s protocol was designed with recommendations from the FDA following a positive type C meeting with the agency earlier this year. In addition to MS, the company has plans to assess the agent in Alzheimer disease, with an investigational new drug application submission expected to be filed by the third quarter of 2023 upon completion of toxicology studies.

“Frequent visits to the clinic for dosing is very difficult for my patients with MS,” principal investigator Tanuja Chitnis, MD, professor of neurology at Harvard Medical School and senior neurologist at Brigham and Women’s Hospital, a founding member of Mass General Brigham Healthcare System, said in a statement. “The ability for patients to dose themselves at home is truly welcome.”

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).