ACTRIMS 2026: Bazedoxifene fails to boost myelin repair in women with MS
Trial focused on menopausal females offers insights into design of future studies
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A representation of a nerve cell with degrading myelin.
- Bazedoxifene, an estrogen-altering drug, failed to promote myelin repair in women with MS.
- The phase 2 trial found the drug safe but ineffective for remyelination in perimenopausal/menopausal women.
- Future research for myelin repair in MS may target younger patients or combination therapies.
Bazedoxifene, a medication that alters the activity of the sex hormone estrogen, was safe and well-tolerated but did not promote myelin repair in women with multiple sclerosis (MS) in a Phase 2 clinical trial.
The findings come from the ReWRAP study (NCT04002934) and were presented last week at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2026, held in San Diego and online.
Although the trial did not meet its main goal, it offered insights into the challenges of testing therapies aiming to boost myelin repair, particularly in women going through menopause or in the years leading up to it, known as perimenopause.
“Perimenopause really represents a clear unmet clinical needs gap in our MS population,” Riley Bove, MD, a neurologist and researcher at the University of California, San Francisco, said in her talk, “ReWrap: A Phase II Delayed Start Myelin Repair RCT.”
Promoting myelin repair a major goal in MS research
MS is an autoimmune disease in which the immune system attacks the myelin sheath, a protective coating around nerve cells that helps electrical signals travel efficiently.
While several therapies are approved to treat MS, most work to reduce inflammatory attacks to prevent new damage to the brain and spinal cord. Existing therapies have a limited ability to repair damaged myelin.
As a result, promoting myelin repair is a major goal in MS research, as it could potentially ease symptoms and help restore some lost functions. Several experimental therapies are being developed to boost remyelination, and some have shown early signs of benefit, but none are yet available to patients.
“There is a clear need for more treatments that are tolerable [and] target different mechanisms,” Bove said.
Through laboratory screening studies, Bove and her colleagues identified bazedoxifene as a potential remyelinating therapy. The medication belongs to a class of compounds called selective estrogen receptor modulators, or SERMs, which can boost the beneficial effects of estrogen in some tissues while blocking unwanted effects in others.
“SERMs … can dial up the wanted effects of estrogen in target tissues such as bone and, in this case, hopefully the brain,” Bove said. At the same time, it can reduce unwanted effects in tissues such as the breast, she added.
Bazedoxifene approved in EU to treat osteoporosis
Bazedoxifene is approved in the European Union for the treatment of osteoporosis, a disease characterized by weak, fragile bones, in postmenopausal women. It is sold in the EU under the name Conbriza. Its active ingredient is also part of the combination therapy Duavee, approved in the U.S. for certain menopause-related symptoms.
Based on these approvals, the researchers designed the ReWRAP trial to test bazedoxifene in women with MS who were in perimenopause or menopause. However, this posed challenges, as previous work has demonstrated that remyelination may be most effective in younger individuals.
“This is kind of a Goldilocks problem, where patients had to be a certain age to be eligible to take [bazedoxifene], but perhaps that age was a little late in the window for myelin repair,” Bove said.
The Phase 2 study enrolled 66 women with relapsing-remitting MS, ages 40 to 60, most of whom were in perimenopause or menopause.
Half of the participants received daily bazedoxifene for six months. The other half received a placebo for the first three months, followed by bazedoxifene for the next three months, in a delayed-start design.
This is kind of a Goldilocks problem, where patients had to be a certain age to be eligible to take [bazedoxifene], but perhaps that age was a little late in the window for myelin repair.
The treatment was safe and well-tolerated, with no severe side effects reported. However, it did not significantly improve myelin water fraction scores, an MRI-based measurement of myelin density and integrity, failing to meet the trial’s main goal.
There were also no meaningful differences between the groups in a composite measure of functional ability that included assessments of walking function, dexterity, cognition, and vision.
The researchers are now analyzing additional measures, including blood biomarkers and other functional outcomes.
While the trial failed to show significant benefits from bazedoxifene, it provides some insights into future trial design. For example, future trials testing SERMs may consider enrolling slightly younger patients, for whom myelin repair approaches are more likely to be effective, treating patients for longer, or exploring a combination with another medication that could enhance the drug’s effects on myelin.
The Multiple Sclerosis News Today team is providing virtual coverage of the ACTRIMS Forum 2026 from Feb. 5-7. Go here to see the latest stories from the conference.
