Ocrelizumab

Ocrelizumab

Monoclonal antibody
Type	Whole antibody
Source	Humanized (from mouse)
Target	CD20
Clinical data
Routes of administration	Intravenous infusion
Legal status	Investigational
Identifiers
CAS Number	637334-45-3
ATC code	none
ChemSpider	none
UNII	A10SJL62JY
Chemical data
Formula	C6494H9978N1718O2014S46
Molar mass	148 kg/mol
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Ocrelizumab is a humanized anti-CD20 monoclonal antibody, hence a CD20 antagonist. It targets mature B lymphocytes^[1] and hence is an immunosuppressive drug candidate. It is under development for multiple sclerosis by Hoffmann–La Roche's subsidiary Genentech, and Biogen Idec.

Clinical trials

It had reached Phase III clinical trials for rheumatoid arthritis^[2] and lupus erythematosus,^[3] and Phase II for multiple sclerosis (MS)^[4] and hematological cancer.^[5]

In March 2010, Roche announced the suspension of clinical trials in rheumatoid arthritis and lupus erythematosus. This step followed excess deaths due to opportunistic infections. Development for multiple sclerosis continues.^[6]

In February 17th, 2016 Food and Drug Administration has granted Breakthrough Therapy Designation for the investigational medicine ocrelizumab for the treatment of people with primary progressive multiple sclerosis ^[7]

Multiple sclerosis

In October 2010, Roche announced 24-week results from the PhII study in relapsing-remitting MS. The drug demonstrated a statistically significant reduction in disease activity as measured by brain lesions (measured by MRI scans) and relapse rate compared to placebo. Both doses (200 mg and 600 mg) were well tolerated.

On October 9th, 2015, Genentech presented interim results of three Phase III clinical trials that look promising.^[8] Disability was reduced at 12 and 24 weeks.^[9]

Ocrelizumab is a slightly modified version of Biogen/Genentech's existing therapy Rituxan/Rituximab. As Rituxan was approaching FDA approval for treatment of multiple sclerosis, it was simultaneously approaching the end of its patent. To avoid the profit loss of a new treatment that could have been available sooner and eventually in a generic form, Rituxan trials were halted and Ocrelizumab trials quickly began.^[10]

See also

• Other CD20 antagonists:
  • Rituximab, a chimeric CD20 antagonist.
  • Ofatumumab (HuMax-CD20) a fully human CD20 antagonist
• BIIB033 (Anti-LINGO-1): another monoclonal antibody designed for treating multiple sclerosis

References

1. K. John Morrow Jr (2008-06-15). "Methods for Maximizing Antibody Yields". Genetic Engineering & Biotechnology News (Mary Ann Liebert, Inc.). p. 36. Retrieved 2008-07-06. (Note: information included in this article only found in table present in print version of article.)
2. Kausar, F; Mustafa, K; Sweis, G; Sawaqed, R; Alawneh, K; Salloum, R; Badaracco, M; Niewold, TB; Sweiss, NJ (2009). "Ocrelizumab: a step forward in the evolution of B-cell therapy". Expert opinion on biological therapy 9 (7): 889–95. doi:10.1517/14712590903018837. PMID 19463076.
3. Clinical trial number NCT00539838 for "A Study to Evaluate Two Doses of Ocrelizumab in Patients With Active Systemic Lupus Erythematosus (BEGIN)" at ClinicalTrials.gov
4. Clinical trial number NCT00676715 for "A Study of the Efficacy and Safety of Ocrelizumab in Patients With Relapsing-Remitting Multiple Sclerosis" at ClinicalTrials.gov
5. Hutas, G (2008). "Ocrelizumab, a humanized monoclonal antibody against CD20 for inflammatory disorders and B-cell malignancies". Current opinion in investigational drugs (London, England : 2000) 9 (11): 1206–15. PMID 18951300.
6. Katie Reid (2010-03-08). Update 2. Roche suspends arthritis treatment after deaths. Reuters. Retrieved 2010-03-08.
7. "U.S. FDA grants Breakthrough Therapy Designation for Roche’s investigational medicine ocrelizumab in primary progressive multiple sclerosis". Hoffmann Roche Ltd. 17 February 2016.
8. First Data From Ocrelizumab Phase 3 Studies in MS. Oct 2015
9. In Third Trial, Ocrelizumab Shows Promise in Progressive MS
10. The shameful story of Rituximab in Multiple Sclerosis