Biotin in MS: Positive Takeaways From Negative Trial Results

Bruce Cree, MD, PhD, MAS

Recently, the results from the SPI2 study (NCT02936037), a follow-up to the successful MS-SPI study (NCT02220933), suggested that high-dose, pharmaceutical-grade biotin (MD1003; MedDay Pharmaceuticals) does not offer benefit for patients with progressive multiple sclerosis (MS) with regard to improved disability or walking speed.^1,2

In total, the study included 642 participants randomized to either 100-mg oral biotin 3 times daily (n = 326) or placebo (n = 316). The prior study appeared to show improved disability outcomes over 12 months with high-dose biotin in patients with progressive MS.

The investigators of SPI2, including Bruce Cree, MD, PhD, MAS, clinical research director, UCSF Multiple Sclerosis Center, and colleagues, noted that as a result of these findings, the therapy cannot be recommended for the treatment of the disease. The data show that for the primary outcome—a composite of the proportion of participants with confirmed improvement in Expanded Disability Status Scale (EDSS) or timed 25-foot walk (TW25) at month 12—just 12% of the biotin group (n = 19) improved compared to 9% of those in the placebo group (n = 29), for an odds ratio (OR) of 1.35 (95% CI, 0.81–2.26; P = .31).

To find out more about what the clinical community can take away from these data despite a negative result, NeurologyLive reached out to Cree. He offered insight into the data and perspective on the result.

NeurologyLive: Do you believe positives can be gleaned from the data despite negative results?

Bruce Cree, MD, PhD, MAS: Yes, the SPI2 study showed that a large multi-center, international randomized controlled, study in non-active, progressive MS patients using diverse clinical, radiographic and biomarkers as relevant endpoints is feasible. Even though the investigational product (MD1003) did not improve outcomes as was hoped, the rigorous study design can help inform future studies that target the unmet need of improving disability outcomes in patients with progressive MS.

The successful recruitment for this trial speaks to the tremendous remaining unmet need for medications that might improve disability in non-active, progressive MS patients.

This was the first multicenter trial in MS that deployed continuous activity monitoring. Several other exploratory endpoints are noteworthy and include MRS, spinal cord imaging, and blood biomarkers. Such elements could be incorporated into future studies of treatments designed as neural protective medications or treatments that might improve disability.

Post-hoc analyses suggest that it is possible had the study been designed differently, that a benefit of MD-1003 might have been seen; however, such a study would be very different from the MS-SPI clinical trial and could not have been designed based on the MS-SPI results.

Were any of the data (secondary outcomes or otherwise) surprising or revealing in any way?

Yes, we were surprised by the absence of a treatment effect given the beneficial effects on the primary and secondary endpoints seen in MS-SPI. That there was no clear benefit in any subgroup or for any secondary or exploratory endpoint was disconcerting, given the MS-SPI’s apparently robust results.

What should the MS clinician community take away from these findings?

SPI2 was not able to show a beneficial effect of high dose biotin in non-active progressive forms of MS. The negative study results in conjunction with the potential serious nature of misinterpretation of abnormal laboratory values does not support MD-1003, and by extension other forms of high dose biotin, as a treatment in progressive MS.

Transcript edited for clarity.

REFERENCE
1. Cree BA, Cutter G, Wolinksy JS, et al. Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. Published October 23, 2020. doi: 10.1016/S1474-4422(20)30347-1
2. MedDay reports top-line data from phase 3 trial “SPI2” for treatment of progressive forms of multiple sclerosis. News release. MedDay Pharmaceuticals. March 10, 2020. Accessed October 29, 2020. businesswire.com/news/home/20200310005779/en/MedDay-Reports-Top-Line-Data-Phase-III-Trial