Safety, tolerability and efficacy of Boswellic acids in relapsing-remitting multiple sclerosis - the SABA proof- of-concept trial

Background: Orally available drugs exhibiting a safe and favour- able side effect profile for the treatment of relapsing-remitting Multiple Sclerosis (RR-MS) are of high interest for patients and treaters. Boswellic acids (BAs), the main biologically active com- pound of frankincense, are orally available and known to exhibit anti-inflammatory activities. Clinical trials with frankincense extracts in rheumatoid arthritis showed very good tolerability and good efficacy in restraining inflammation, while the effect of BAs in RR-MS is unknown so far. Objectives: We perform a Phase IIa bicentric open-label baseline- to-treatment study with the standardized frankincense extract BOSWELAN® to test the safety, tolerability and efficacy of BAs in RR-MS patients. Methods: The study is conducted under GCP. One major inclu- sion criteria is the presence of at least 2 new Gadolinium- enhancing (Gd+) lesions in monthly MRI during a 3-month screening phase. Treatment is initiated by an individualized dose finding to identify the highest well tolerated BOSWELAN® dose for each patient. Primary outcome is the number of new Gd+ lesions in monthly MRIs between months 5 and 8 of the treatment phase compared to 4 screening MRIs. Results: 80 patients were screened at two centers to include 37 patients in the SABA trial. 6 patients terminated early due to non- compliance with the study protocol (n=3) or did start licensed immunotherapy because of relapse activity (n=3). Until now 23 patients have reached the primary endpoint of the treatment phase (month 8). Boswellic acids were very well tolerated at the highest dose of 4800mg per day which is the treatment dose for the major- ity of study patients (87%). There were no changes of laboratory parameters, in particular no changes in blood cell counts or liver enzymes due to the intake of BAs. Adverse events (AEs) were primarily mild (59% of all AEs) or moderate (39% of all AEs) and comprised predominantly gastrointestinal symptoms within the first four weeks (dose escalation phase). These declined almost completely to baseline frequencies afterwards. MRI disease activ- ity was reduced by 63,8% in the number of new Gd+ lesions and by 62,4% in the number of new T2 lesions between screening and treatment phase (p < 0.05). Conclusions: Up to now BOSWELAN shows a very good safety profile and high patient acceptance. Together with MRI results of the ongoing study a randomized placebo-controlled phase 2 trial in RR-MS seems justified to further evaluate BAs as a novel treat- ment option in RR-MS.