Obexelimab stops new MS brain lesions in clinical trial, data show
New lesions almost completely prevented in trial's 1st 12 weeks
Obexelimab, a therapy Zenas Biopharma is developing for a range of autoimmune diseases, almost completely prevented the formation of new inflammatory lesions in adults with relapsing forms of multiple sclerosis (MS) in the first three months of a clinical trial.
That’s according to data from the first part of MoonStone (NCT06564311), a Phase 2 clinical trial testing obexelimab as a weekly, 250 mg subcutaneous (under-the-skin) injection in adults with relapsing-remitting MS or active secondary progressive MS.
Participants were randomly assigned to receive obexelimab or a placebo for 12 weeks (about three months) in the first part of the trial. In a second part, all are receiving obexelimab for another 12 weeks. The company said it expects to have 24-week data early next year.
These additional data “may inform obexelimab’s potential impact on disability progression and help us determine next steps for future development of obexelimab in relapsing MS,” Lisa von Moltke, MD, head of research and development at Zenas, said in a company press release.
After the 24 weeks, patients may join an open-label extension and continue on obexelimab for a year.
Curtailing cell activity
MS occurs when the immune system produces antibodies that mistakenly attack myelin, the protective covering around nerve cells, in the brain and spinal cord. These autoimmune attacks damage both myelin and nerve cells, causing lasting inflammation that can lead to disability worsening.
Obexelimab targets B-cells — the immune cells that produce antibodies — including those involved in autoimmune disease. It binds to two proteins on B-cells, CD19 and FcgammaRIIb, which is expected to reduce the production of antibodies and other inflammatory molecules. Unlike other approaches, obexelimab reduces the activity of B-cells rather than destroying them.
The fully enrolled Phase 2 clinical trial recruited 116 adults with relapsing forms of MS. The main goal was to monitor new gadolinium-enhancing lesions on MRI scans, which represent lesions with active inflammation.
Results showed that, compared with a placebo, obexelimab almost completely suppressed the formation of new lesions with active inflammation. The cumulative number of new inflammatory lesions was reduced by 95% over eight weeks and maintained throughout 12 weeks.
On average, patients treated with obexelimab had significantly fewer new inflammatory lesions per MRI scan than those on a placebo (0.01 vs. 0.23). Obexelimab also reduced the number of new or enlarging lesions over weeks eight and 12.
“These profound MoonStone trial results, including the near elimination of new [active] lesions, provide strong evidence of the deep and sustained inhibitory mechanism of obexelimab and further validate the potential for obexelimab to become a meaningful therapy across multiple autoimmune diseases,” said Lonnie Moulder, founder and CEO of Zenas.
The safety profile of obexelimab was consistent with what has been seen in earlier clinical testing for other autoimmune diseases. Some patients experienced infections and exaggerated immune reactions, most commonly mild injection site reactions.
“The observed clinical activity in the MoonStone trial, combined with obexelimab’s unique inhibitory mechanism of action, subcutaneous self-administration and tolerability profile, position obexelimab as a potential option to broadly address the [disease-causing] role of B cells in autoimmune diseases,” said von Moltke, who doubles as Zenas’ chief medical officer.
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