Otelixizumab
Monoclonal antibody | |
---|---|
Type | Whole antibody |
Source | Template:Infobox drug/mab source |
Target | CD3E |
Identifiers | |
CAS Number | 881191-44-2 |
ATC code | none |
Chemical data | |
Formula | C6448H9954N1718O2016S42 |
Molar mass | 145.1 kDa[[Script error: No such module "String".]] |
Otelixizumab, also known as TRX4, is a monoclonal antibody[1], which is being developed for the treatment of type 1 diabetes and other autoimmune diseases. The antibody is being developed by Tolerx, Inc. in collaboration with GlaxoSmithKline and is being manufactured by Abbott Laboratories.[2][3]
Mechanism of action
Otelixizumab is one of several investigational monoclonal antibodies that target CD3, a T lymphocyte receptor involved in normal cell signaling. More specifically, otelixizumab targets the epsilon chain of CD3. Data suggest that the drug works by blocking the function of effector T cells, which mistakenly attack and destroy insulin-producing beta cells while stimulating regulatory T cells, which are understood to protect against effector T cell damage, thus preserving the beta cells' normal ability to make insulin.[4]
Proof of concept was established in a randomized, placebo-controlled Phase 2 study. These data demonstrated otelixizumab’s ability to preserve beta cell function, as measured by C-peptide, in patients up to 18 months after dosing, as well as reduce the need for delivered insulin to maintain glucose control.[5][6]
Clinical progress
The efficacy and safety of otelixizumab for the treatment of autoimmune type 1 diabetes is currently being studied in a pivotal Phase 3 study called DEFEND (Durable-response therapy Evaluation For Early or New-onset type 1 Diabetes).[7] DEFEND is a randomized, placebo-controlled Phase 3 trial designed to enroll approximately 240 adult patients, age 18 to 35, with newly diagnosed autoimmune type 1 diabetes. DEFEND is being conducted at multiple centers in North America and Europe. The trial is designed to evaluate whether a single course of otelixizumab, administered not more than 90 days after the initial diagnosis, will reduce the amount of administered insulin required to control blood glucose levels by inhibiting the destruction of beta cells.[8]
Orphan drug status
Otelixizumab has been granted "orphan drug" status by the U.S. Food and Drug Administration.[9]
Chemistry
As a monoclonal antibody, otelixizumab consists of two heavy chains and two light chains. The heavy chains are humanized γ1 (gamma-1) chains from rats, making otelixizumab an immunoglobulin G1. The light chains are chimeric human/rat λ (lambda) chains.[10]
References
- ↑ Bolt, S., Routledge, E., Lloyd, I., Chatenoud, L., Pope, H., Gorman, S., Clark, M. & Waldmann, H. (1993). The generation of humanized, non-mitogenic CD3 monoclonal antibody which retains in-vitro immunosuppressive properties. Europ. J. Immunol. 23, 403-411.
- ↑ Windhover Information “GSK buys rights to Tolerx's diabetes antibody otelixizumab”
- ↑ (PDF). Thomson Bioworld. 30 November 2005. p. 6 http://www.bioworld.com/img/bwt11302005sample.pdf. Retrieved 2 December 2009. Missing or empty
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(help) - ↑ Chatenoud, L; Bluestone, JA (2007). "CD3-specific antibodies: a portal to the treatment of autoimmunity". Nat Rev Immunol. 7 (8): 622–32. doi:10.1038/nri2134. PMID 17641665.
- ↑ Chatenoud, L.; Vandemeulebroucke, E; Ziegler, AG; Mathieu, C; Kaufman, L; Hale, G; Gorus, F; Goldman, M; Walter, M (June, 2005). "Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes". N Engl J Med. 352 (25): 2598–608. doi:10.1056/NEJMoa043980. PMID 15972866. Check date values in:
|date=
(help) - ↑ Kaufman, A; Herold, KC (24 March, 2009). "Anti-CD3 mAbs for treatment of type 1 diabetes". Diabetes Metab Res Rev. 25 (4): 302–6. doi:10.1002/dmrr.933. PMID 19319985. Check date values in:
|date=
(help) - ↑ From ClinicalTrials.gov, a Service from the U.S. National Institutes of Health
- ↑ www.DefendAgainstDiabetes.com
- ↑ Mass High Tech, May 16, 2008, “N.E. drug makers find individual paths into growing diabetes arena”
- ↑ "Recommended INN List 60" (PDF). WHO Drug Information. 22 (3). 2008.
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