Remelyinating Drug Bazedoxifene Fails to Meet End Points in Phase 2 Study of Multiple Sclerosis

Late-breaking data from the phase 2 ReWRap trial (NCT04002934) showed that bazedoxifene acetate (BZA) did not meet its primary or secondary remyelination endpoints in women with relapsing multiple sclerosis (RMS) at risk for axonal loss and disease progression. Although the treatment was well tolerated, the agent did not demonstrate statistically significant differences across any efficacy outcomes.

“From a safety and tolerability standpoint, we we’re very encouraged,” senior study author told NeurologyLive®. “From an efficacy standpoint, when we looked at our main trial outcome, which was effect on myelin water fraction, we did not see any statical improvement.”

Presented at the 2026 Americas Committee for Treatment & Research in Multiple Sclerosis (ACTRIMS) Forum, held February 5-7 in San Diego, California, early-start (BZA) and delayed-start (placebo) groups were well matched across all baseline characteristics. At 3 months, the BZA group showed greater numerical improvements than the placebo group for the primary outcome of myelin water fraction (MWF) and for the MS Functional Composite z-score, yet these differences were not statically significant. The BZA group also demonstrated improved P100 latency in a subgroup of participants with chronic optic neuropathy.

In terms of safety, no severe adverse events (AEs) were reported. Overall, rates of AEs were comparable between groups, as treatment satisfaction was high, and no relapses or new brain MRI lesions were observed during the study period.

The single-center, double blind, randomized, controlled, delayed-start clinical trial enrolled 65 total patients, 63 of whom completed the trial (96.9%), aged 45-60 years and ranged from 0-6 on the Expanded Disability Status Scale (EDSS). Postmenopausal patients over 40 were recruited as well.

Participants were then randomized 1:1 and stratified by age (40–55 vs 56–60 years) to either an early-start group, which received 6 months of BZA, or a delayed-start group, which received 3 months of placebo followed by 3 months of BZA. The primary endpoint was change in myelin water fraction (MWF) within the corpus callosum, as measured by MRI. Secondary endpoints included a range of clinical, electrophysiological, digital, and patient-reported outcomes, while tertiary endpoints focused on safety and tolerability.

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Study authors decided to administer BZA, a selective estrogen receptor modulator (SERM) approved by the European Medicine Agency (EMA), because of its remyelinating repair potential in human populations. For context, the treatment is currently approved for postmenopausal osteoporosis and has previously demonstrated remyelinating effects in animal models. Relative to other younger myelin repair trial populations, study authors noted that menopausal women face increased risk of axonal loss, which could influence their potential for myelin repair.

In related research led by Riley Bove, MD, associate professor at the University of California, San Francisco, investigators evaluated the feasibility, tolerability, and symptom response in a combination of bazedoxifene and conjugated estrogen, Duavee, in peri- and postmenopausal women with MS who experienced vasomotor symptoms. Because most women develop MS before menopause and hot flashes may worsen neurologic symptoms, the phase 1b/2a, double-blind, randomized controlled trial was designed to explore whether hormone-based therapy could offer symptomatic benefit while remaining safe.

Although enrollment was protracted over 34 months, primarily due to safety concerns surrounding hormone therapy, investigators reported high treatment satisfaction and adherence in the active group, along with favorable retention (87%). No participants in the treatment arm developed new MRI lesions, liver function remained normal across both groups, and adverse effects were minimal.

At 2 months, patients receiving the treatments reported numerically lower scores on the Hot Flash Related Daily Interference scale compared with placebo, though between-group differences were not statistically significant. Study authors concluded that, with appropriate education and screening, these findings support the feasibility of a longer, adequately powered trial to determine whether a therapy proven for menopausal symptoms could also improve MS-related function in menopausal women.

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REFERENCES
1. Nylander A, Akula A, Anderson A, et at. ReWrap: A Phase II Delayed Start Myelin Repair RCT. Presented at the 2026 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 5-7, 2026; San Diego, California.
2. Bove R, Anderson A, Rowles W, et al. A hormonal therapy for menopausal women with MS: A phase Ib/IIa randomized controlled trial. Mult Scler Relat Disord. 2022;61:103747. doi: 10.1016/j.msard.2022.103747