Experimental MS Oral Antibiotic Combination Therapy Showing Promise in Phase 2a Study, RedHill Biopharma Reports

RedHill Biopharma, Ltd. recently announced promising interim results from its ongoing CEASE-MS Phase 2a clinical trial evaluating the safety and efficacy of a fixed dose of RHB-104 as an add-on therapy for the treatment of relapsing-remitting multiple sclerosis (RRMS).

RHB-104 consists of an oral capsule formulation of an antibiotic combination therapy — 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine — with strong intracellular, anti-mycobacterial, and anti-inflammatory properties. Originally developed for the treatment of Crohn’s disease, this drug is now being pursued as a complementary therapy for RRMS due to its potential anti-inflammatory and neuroprotective activity.

The CEASE-MS study, “Proof of Concept Study of RHB-104 as Add-On Therapy to Interferon Beta-1a in Relapsing Remitting Multiple Sclerosis,” is a proof-of-concept clinical trial also exploring the efficacy of RHB-104 as an adjuvant therapy to interferon beta-1a in 18 patients with RRMS. The recently announced results refer to safety and clinical evidence after 24 weeks of treatment.

Annualized relapse rate (ARR) at 24 weeks was 0.288 in the modified intent-to-treat (mITT) population (all study participants), and 0.0 in the per-protocol (PP) population (the cohort analyzed). These results compare favorably with previously reported data of interferon beta-1a therapies Avonex and Rebif, RedHill announced in a company press release.

Also at 24 weeks, 88 percent of the mITT patient population and 100 percent of the PP group were relapse free, compared with Rebif (75%) and with Avonex (63%) as standalone therapies. Moreover, no patients in the CEASE-MS study relapsed after week eight of treatment, and no increase in total Expanded Disability Status Scale (EDSS), a measure of disability in MS, was observed in any patient during the treatment period.

Results also indicated a reduction in MRI T2 lesion volume, a definition of burden of disease and indicator of response and progression in RRMS, at 24 weeks of treatment with RHB-104 as compared to baseline. Such results again compared favorably to previous data for Avonex and Rebif treatment. Importantly, RHB-104 was found to be safe and well-tolerated, and no drug-related serious side-effects were observed.

“We are very pleased with the interim results from the ongoing CEASE-MS Phase IIa proof-of-concept study with RHB-104 for relapsing-remitting multiple sclerosis (RRMS). The initial findings from the study, including safety, clinical and MRI, support the therapeutic potential of RHB-104 as add-on therapy in RRMS,” said Dr. Ira Kalfus, MD, medical director of RedHill and for the CEASE-MS study. “Although designed as an exploratory proof-of-concept study in a very small patient population and not powered for efficacy, the study interim results demonstrate positive safety data and clinical signals, supporting additional studies to better investigate the therapeutic potential of RHB-104 in RRMS.”

Dr. Radi Shahien, MD, principal investigator of the CEASE-MS study, added: “RRMS is a devastating disease with no known cure, limited treatment options and unknown cause, hence the importance of the development of RHB-104, an intracellularly acting, anti-mycobacterial, anti-inflammatory and orally administered drug candidate. CEASE-MS is … intended to investigate the groundbreaking hypothesis that a bacterial induced dysregulated immune system plays a critical role in the pathogenesis of MS. RedHill’s CEASE-MS study with RHB-104 is the first clinical study to evaluate the therapeutic potential of a triple antibiotic combination therapy, and specifically these intracellularly acting antibiotics, as add-on therapy in RRMS. The initial analysis of the study’s interim results provides encouraging clinical signals as well as important and reassuring safety data. In particular, the reduction of total T2 lesion burden over baseline, a key MS disease burden measurement, as well as relapse-free and stable EDSS data, are positive and meaningful signals, particularly given the small patient population in the study and the early time point of the data generated to date. I find the interim results very promising and am encouraged by the potential efficacy of RHB-104 in treating MS. I look forward to the completion of the study, further analyses and presentation of the final data at the appropriate international medical and academic forums.”

RedHill Biopharma, Ltd. is an Israeli company focused on the development and commercialization of oral-administered small-molecule medicines for inflammatory and gastrointestinal diseases.