Multiple Sclerosis Remyelination Medication granted Expanded Access by the FDA.

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NHE
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Re: Multiple Sclerosis Remyelination Medication granted Expanded Access by the FDA.

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Many PwMS have lesions on their spinal cord. Elezanumab may offer hope for healing those lesions.

Delayed administration of the human anti-RGMa monoclonal antibody elezanumab promotes functional recovery including spontaneous voiding after spinal cord injury in rats
Neurobiol Dis. 2020 Sep;143:104995.

Spinal cord injury (SCI) often results in permanent functional loss due to a series of degenerative events including cell death, axonal damage, and the upregulation of inhibitory proteins that impede regeneration. Repulsive Guidance Molecule A (RGMa) is a potent inhibitor of axonal growth that is rapidly upregulated following injury in both the rodent and human central nervous system (CNS). Previously, we showed that monoclonal antibodies that specifically block inhibitory RGMa signaling promote neuroprotective and regenerative effects when administered acutely in a clinically relevant rat model of thoracic SCI. However, it is unknown whether systemic administration of RGMa blocking antibodies are effective for SCI after delayed administration. Here, we administered elezanumab, a human monoclonal antibody targeting RGMa, intravenously either acutely or at 3 h or 24 h following thoracic clip impact-compression SCI. Rats treated with elezanumab acutely and at 3 h post-injury showed improvements in overground locomotion and fine motor function and gait. Rats treated 24 h post-SCI trended towards better recovery demonstrating significantly greater stride length and swing speed. Treated rats also showed greater tissue preservation with reduced lesion areas. As seen with acute treatment, delayed administration of elezanumab at 3 h post-SCI also increased perilesional neuronal sparing and serotonergic and corticospinal axonal plasticity. In addition, all elezanumab treated rats showed earlier spontaneous voiding ability and less post-trauma bladder wall hypertrophy. Together, our data demonstrate the therapeutic efficacy of delayed systemic administration of elezanumab in a rat model of SCI, and uncovers a new role for RGMa inhibition in bladder recovery following SCI.

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NHE
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Re: Multiple Sclerosis Remyelination Medication granted Expanded Access by the FDA.

Post by NHE »

Expanded access is only available for the following conditions.

• Acute Spinal Cord Injury (SCI)
• Acute Ischemic Stroke

Here is personal communication I’ve received directly from a study site coordinator involved with the AbbVie clinical trial for MS.

“Here is the info regarding the research study AbbVie M18-918 that we conducted with the study drug elezanumab vs placebo.
 
The AbbVie study ended prematurely. The trial enrolled 208 RRMS patients over 38 sites. The safety profile of the study drug appeared to be very good. Adverse events were distributed the same across all three treatment groups (high dose drug, low dose drug, and placebo). Serious Adverse events (ie hospitalizations) were related to Covid-19 infections and/or MS relapse, not study drug events. One death occurred in the study population. The patient was randomized to placebo and suffered a pulmonary embolism with no relationship to participation in the study.

The efficacy data was based on the Overall Response Score (ORS) in the study which is calculated from primary endpoints: the EDSS, two timed 25 foot walks, and the 9 hole peg test trials done twice each administration on the dominant and non-dominant hands. The study drug in high and low dose groups did not meet the primary endpoints for improvement in function or a reduction in disability compared to placebo.
 
There are currently no plans to further investigate this drug in MS. It will still be studied in spinal cord injury. And, a subset of patients saw improvement in their low contrast visual acuity on study drug and that may be further explored.”
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