Genentech’s Ocrevus (ocrelizumab) reduces levels of cerebrospinal fluid biomarkers that denote nerve cell damage in multiple sclerosis patients, a Phase 3 clinical trial shows.
Researchers will present the results at the American Academy of Neurology’s annual meeting in Los Angeles, April 21-27. The presentation will be titled “Interim Analysis of the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Study in Multiple Sclerosis (MS).”
Biomarkers in cerebrospinal fluid can be an indication of the health of the central nervous system. Not only can they help researchers understand the mechanisms underlying MS but they can also offer insight into therapies’ effectiveness.
Two cerebospinal fluid biomarkers are the neurofilament light chain (NfL) and immune system white blood cells known as lymphocytes.
Genentech is conducting the Phase 3 OBOE trial (NCT02688985) to gain a better understanding of Ocrevus’s mechanism of action in relapsing and primary progressive MS patients.
Researchers are giving the two groups 600-mg intravenous doses of Ocrevus every 24 weeks.
To see how Ocrevus affects cerebrospinal fluid biomarkers, the team inserts a needle into patients’ spinal canal before the treatment and at defined points thereafter — 12, 24, or 52 weeks.
Researchers are using another group of relapsing MS patients as controls. They will have two spinal taps — called lumbar punctures — 12 weeks apart before starting Ocrevus.
The research team did an interim analysis that covered Ocrevus-treated patients 12 and 24 weeks after the start of treatment and the relapsing MS control group before treatment. The analysis covered 40 patients.
Part of the analysis dealt with the therapy’s safety. It covered all 82 patients who had been taking part in the trial to that point.
A key finding was a 24 percent drop in median NfL levels in Ocrevus-treated patients’ cerebrospinal fluid at 12 weeks and a 47 percent drop at 24 weeks.
Researchers also saw a decline in two types of Ocrevus-treated patients’ immune cells. The number of B lymphocytes called CD19+ B-cells dropped by 86 percent at 12 weeks and 82 percent at 24 weeks. Scientists have linked these cells to the development of MS.
Meanwhile, the number of CD3+ T-cells decreased by 60 percent at week 12 and 67 percent at week 24.
Ocrevus’s safety profile matched that seen in previous Phase 3 trials, researchers said — and in general patients tolerated it well.
There were no serious infections, malignancies or deaths. Forty-four percent of patients reported infusion-related reactions. Only one serious adverse event occurred —a seizure.
Overall, “NfL decreased at 12 weeks, appeared to decrease further at 24 weeks, and correlated with CSF [cerebrospinal fluid] B- and T-cell numbers,” researchers wrote. This suggested “continued reduction in axonal [nerve celll] injury with ocrelizumab [Ocrevus] treatment, and that levels of CSF inflammatory cells may predict neuronal injury,” they wrote.
Researchers continue to recruit patients for the OBOE trial. For more information, please visit this link. Final results of the trial are expected in early 2019.