Daclizumab

Daclizumab

Monoclonal antibody
Type	Whole antibody
Source	Humanized (from mouse)
Target	CD25
Clinical data
Trade names	Zenapax
AHFS/Drugs.com	monograph
Pregnancy category	C
Legal status	US: ℞-only European marketing authorisation withdrawn
Routes of administration	Intravenous
Pharmacokinetic data
Biological half-life	20 days (11–38 days)
Identifiers
CAS Number	152923-56-3
ATC code	L04AC01
DrugBank	DB00111
ChemSpider	none
UNII	CUJ2MVI71Y
ChEMBL	CHEMBL1201605
Chemical data
Formula	C6332H9808N1678O1989S42
Molar mass	142,612.1 g/mol
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Daclizumab (trade name Zenapax) is a therapeutic humanized monoclonal antibody. It is used to prevent rejection in organ transplantation, especially in kidney transplants. The drug is also under investigation for the treatment of multiple sclerosis.

Daclizumab works by binding to CD25, the alpha subunit of the IL-2 receptor of T cells. The drug is marketed in the US, but not in Europe.

Uses

Prevention of organ transplant rejection

Daclizumab is given in multiple doses, the first 1 hour before the transplant operation and 5 further doses given at two week intervals after the transplant. These saturate the receptors and prevent T cell activation and thus prevent formation of antibodies against the transplant.

Like the similar drug basiliximab, daclizumab reduces the incidence and severity of acute rejection in kidney transplantation without increasing the incidence of opportunistic infections.

Daclizumab usage may also be indicated in place of a calcineurin-inhibitor (ciclosporin or tacrolimus) during the early phase after kidney transplantation, when the kidney is recovering and vulnerable to calcineurin-inhibitor toxicity. This has been shown to be beneficial in non-heart beating donor kidney transplantation.

In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) has recommended its use be considered for all kidney transplant recipients.

Multiple sclerosis

In 2006 it began a Phase II clinical trial that finished in 2007 as a possible multiple sclerosis (MS) treatment. Participants were nine patients with multiple sclerosis not controlled with interferon. Daclizumab was effective in reducing lesions and improving clinical scores.^[1] As of September 2013, the drug is in Phase III trials for this indication.^[2][3]

Autoimmune diseases

Daclizumab has also been used to slow the progression of autoimmune diseases, particularly that of birdshot chorioretinopathy.^[4]

Adverse effects

Common side effects with a frequency of at least 10% include sleeplessness, tremor, headache, arterial hypertension, dyspnoea, gastrointestinal side effects and oedema. In rare cases, the drug can cause severe anaphylaxis.^[5]

History

Daclizumab was developed by PDL Biopharma, building on research at the National Institutes of Health (NIH).^[6] Since December 1997, it is marketed by Hoffmann-La Roche in the US.

In April 2008, Hoffmann-La Roche submitted an application to have its marketing authorisation withdrawn in the EU for commercial reasons. The drug faced diminishing market demand, according to the company. There were no safety concerns with its use. As of January 2009, its marketing authorisation has been withdrawn and the product discontinued completely.^[7][8]

References

1. Rose JW, Burns JB, Bjorklund J, Klein J, Watt HE, Carlson NG (2007). "Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results". Neurology 69 (8): 785–789. doi:10.1212/01.wnl.0000267662.41734.1f. PMID 17709711.
2. Clinical trial number NCT01064401 for "Efficacy and Safety of Daclizumab High Yield Process Versus Interferon β 1a in Patients With Relapsing-Remitting Multiple Sclerosis ((DECIDE))" at ClinicalTrials.gov
3. Clinical trial number NCT01462318 for "An Immunogenicity and Pharmacokinetics (PK) Study of DAC HYP Prefilled Syringe in Relapsing Remitting Multiple Sclerosis (RRMS) (OBSERVE)" at ClinicalTrials.gov
4. Sobrin L, Huang JJ, Christen W, Kafkala C, Choopong P, Foster CS (2008). "Daclizumab for treatment of birdshot chorioretinopathy". Arch Ophthalmol. 126 (2): 186–191. doi:10.1001/archophthalmol.2007.49. PMID 18268208.
5. "EPAR for Zenapax" (PDF). European Medicines Agency. 2007.
6. Tsurushita, N.; Hinton, P. R.; Kumar, S. (2005). "Design of humanized antibodies: From anti-Tac to Zenapax". Methods 36 (1): 69–83. doi:10.1016/j.ymeth.2005.01.007. PMID 15848076.
7. British National Formulary, Edition 57
8. EMEA: Withdrawal of the marketing authorisation in the European Union