MEDI-551 (inebilizumab) is a humanized monoclonal antibody that is being developed by MedImmune (part of AstraZeneca) as a treatment for neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD). MEDI-551 was previously under development as a treatment for relapsing-remitting multiple sclerosis (RRMS).
In March 2016, the U.S. Food and Drug Administration (FDA) granted MEDI-551 orphan drug designation by for the treatment of NMO and NMOSD.
How MEDI-551 works
Like multiple sclerosis (MS), NMO is caused by the immune system mistakenly targeting healthy nerves. In NMO, immune cells, such as B-cells, attack optic nerves and the spinal cord, causing inflammation. This leads to nerve damage and a loss of vision among many other symptoms, which can be fatal.
MEDI-551 is an antibody, a type of protein designed to bind to a specific target, called CD19. CD19 is a protein that is present on the outside of B-cells that regulates their activation. Binding MEDI-551 to CD19 triggers antibody-dependent cellular cytotoxicity (ADCC), a process that results in the death of the B-cell. This results in fewer B-cells available to contribute to the damaging immune response causing NMO.
MEDI-551 has the potential to be a more effective therapy than rituximab, another antibody being investigated to deplete B-cells. Rituximab targets CD20, which works similarly to CD19. However, CD20 is expressed at lower levels and is not found on all B-cells. A particular type of B-cell called plasmablasts, which are heavily involved in the pathogenesis of NMO, do not have CD20 but do have CD19. This means that MEDI-551 is able to target these cells.
MEDI-551 in clinical trials
Results of preclinical trials in mice published in the scientific journal International Immunopharmacology confirmed that treatment with MEDI-551 leads to a reduction in B-cells. It also suggested that simultaneous treatment with rituximab may result in the B-cells being depleted for longer. This confirms the mechanism of action of MEDI-551 and confirms its potential as a treatment for NMO.
A completed randomized, placebo-controlled Phase 1 study (NCT01585766) assessing the safety and tolerability of MEDI-551 administered as an intravenous (inside a vein) or subcutaneous (under the skin) injection in patients with RRMS showed promising results. Two intravenous infusions with MEDI-551 (at 30 mg, 100 mg, or 600 mg) or a single dose injected under the skin (60 mg or 300 mg) led to a rapid and sustained depletion of B-cells. Patients treated with MEDI-551 had a reduced number of new lesions developing compared to those treated with a placebo. These results were presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in 2015.
Most of the adverse side effects of MEDI-551 observed in the Phase 1 study were fever, the common cold, oral herpes, and increased blood pressure.
A Phase 2/3, randomized, double-blind, placebo-controlled clinical trial (NCT02200770) called N-MOmentum is currently recruiting participants at multiple locations worldwide. The trial intends to assess the safety and effectiveness of intravenously-administered MEDI-551 treatment compared to a placebo over an initial 197 days. Following this, the patients will have the option to enter a 12-month open-label safety follow-up trial investigating the long-term safety of the drug.
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