Daclizumab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized(frommouse) |
| Target | CD25 |
| Clinical data | |
| Trade names | Zinbryta (multiple sclerosis) Zenapax (acute transplant rejection, discontinued in 2009) |
| AHFS/Drugs | zinbryta |
| Pregnancy category |
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| Routes of administration | Subcutaneous injection,Intravenous |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokineticdata | |
| Bioavailability | 90% |
| Metabolism | Proteases |
| Eliminationhalf-life | 21 days (11–38 days) |
| Identifiers | |
| CAS Number | |
| DrugBank | |
| ChemSpider |
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| UNII | |
| KEGG | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C6332H9808N1678O1989S42 |
| Molar mass | 142612.39g·mol−1 |
  (what is this?)(verify) | |
Daclizumab(trade nameZinbryta) is a therapeutic humanizedmonoclonal antibodywhich was used for the treatment of adults with relapsing forms ofmultiple sclerosis(MS). Daclizumab works by binding toCD25,the Alpha subunit of theIL-2 receptorofT-cells.
In March 2018, it was voluntarily withdrawn from the market byBiogenandAbbvieafter reports ofautoimmuneencephalitisin Europe.[4][5][3]
Medical uses
[edit]Daclizumab was used to treat adults with relapsing forms ofmultiple sclerosis.[6]It is administered subcutaneously.[7]
In clinical trials, decreases of 45% in annualized relapse rate have been reported, as well as a 41% reduction in the proportion of patients who relapsed, and a 54% reduction in the number of new lesions.[7]A 2013Cochranesystematic reviewconcluded that there was insufficient evidence to determine the efficacy of daclizumab relative to placebo in people withrelapsing-remitting MSand, prior to its being discontinued, the need to investigate longer lengths of treatment and follow-up.[8]
Discontinued use
[edit]Daclizumab was approved and used to prevent acute rejection of kidney transplant, along with cyclosporine and corticosteroids.[9]For that indication, side effects with a frequency of at least 10% included sleeplessness,tremor,headache,arterial hypertension,dyspnoea,gastrointestinal side effects andoedema.In rare cases, the drug could cause severeanaphylaxis.[10]
Contraindications
[edit]In the US, daclizumab (while approved) was contraindicated in people with liver impairment, including significantly elevated liver enzymes (ALT,AST) andautoimmune hepatitis.[11]
TheEuropean Medicines Agency(EMA) originally approved the drug without any contraindications apart from knownhypersensitivity,[12]but required Biogen to implement a hepatic risk management guide for physicians.[13]In July 2017, the EMA has issued a provisional contraindication for patients with pre-existing liver disease or liver impairment.[14]The marketing authorisation was withdrawn in the EU on 27 March 2018. An EMA review concluded that the medicine poses a risk of serious and potentially fatal immune reactions affecting the brain, liver and other organs.[15]
Adverse effects
[edit]In clinical trials for MS, there were no treatment-related deaths or increased risk of cancer; side effects that occurred more frequently with daclizumab versus interferon included infections (65% versus 57%), skin rashes (37% versus 19%) and liver complications (approximately 18% versus 12%).[7]
Interactions
[edit]As an antibody, daclizumab is expected to have a very low potential forpharmacokineticinteractions with other drugs.[12]
Pharmacology
[edit]Mechanism of action
[edit]Daclizumab blocks IL-2 receptors containing the Alpha subunit (CD25), which include the high-affinity receptors. Medium-affinity receptors, on the other hand, consist of two beta subunits (CD122) and are not affected by daclizumab. While the exact mechanism is unknown, the net effect is a reduction of T-cell responses and expansion ofCD56brightnatural killer cells.[12]
Pharmacokinetics
[edit]Aftersubcutaneous injectionof a single dose, daclizumab has abioavailabilityof about 90% and reaches highestblood plasmalevels after 5 to 7 days. Given every four weeks, steady state concentrations are found after the fourth dose. It is expected that daclizumab, like other antibodies, is degraded byproteasesto peptides and finally amino acids, and that it does not interact withcytochrome P450liver enzymes.[12]
Thebiological half-lifeis 21 days. Patients who developed antibodies against daclizumab eliminated it 19% faster.[12]
History
[edit]Daclizumab was created by scientists atPDL BioPharma(called "Protein Design Labs" at that time) byhumanizingthe mouse mAb called anti-Tac, which targetsCD25,the IL-2 receptor α chain; it blocks the interaction ofIL-2with the IL-2 receptor and prevents activation ofT cells.[16]Anti-Tac had been discovered by Thomas A. Waldmann, M.D., chief of the Metabolism Branch at theNational Cancer Instituteand his team, and they had conducted animal studies and a small clinical trial of anti-Tac in people with T-cell leukemia, with promising results, but people quickly developed their own antibodies rejecting the mouse protein; Waldman, and his colleagues then approached Protein Design Labs to humanize the antibody.[17]PDL and the NIH scientists then approachedRoche,a leader in transplant medicine development, to get the drug developed and approved, as PDL didn't have the resources to actually bring the product to market.[17]In March 2018 the drug was removed from the market worldwide.
In December 1997 daclizumab was approved by the FDA for use in preventing acute rejection of kidney transplants, in combination with ciclosporin and corticosteroids; it was the first humanized antibody approved anywhere in the world.[18][19]At launch, the average wholesale price for the drug was estimated to be $6,800 for five doses and it was estimated that annual sales would be between $100 million and $250 million within five years of the launch and it was thought that the drug's use would be expanded for use in other organ transplants.[19]It was approved in Europe in 1999.[20]
PDL began clinical trials of daclizumab on its own, and in September 2004 after the drug had shown promise in a Phase II trial, PDL and Roche agreed to expand their relationship to include codevelopment of daclizumab for asthma and other respiratory conditions.[21]In August 2005, PDL andBiogen Idecagreed to collaborate to develop daclizumab in indications outside the fields of organ rejection and respiratory disease.[22]In November 2005 Roche and PDL agreed to try to develop a formulation of daclizumab that would be useful as asubcutaneous injectionfor longterm maintenance in organ transplant.[23]The next year Roche and PDL announced that the collaboration for all indications was ending,[24]and in 2009 it announced that it was discontinuing Zenapax worldwide "in view of available alternative treatments and the diminishing market demand" and "not due to any safety issue."[25][26]
in 2008 PDL spun out its active development programs into a company called Facet Biotech and development of daclizumab for multiple sclerosis and the partnership with Biogen was included in that spinout.[27][28]In 2009 Biogen attempted a hostile buy out of Facet for $350M;[29]Facet rejected that offer and was purchased byAbbviefor $450 million in cash the next year.[30]In May 2016 the FDA approved daclizumab for the treatment of relapsing multiple sclerosis in adults in 2016 under the trade name Zinbryta, with requirements for postmarketing studies and to submit a formal Risk Evaluation and Mitigation Strategy.[6][31]
Research
[edit]Daclizumab has been studied in a small clinical trial of people withbirdshot chorioretinopathy.[32]
References
[edit]- ^"Prescription medicines: registration of new chemical entities in Australia, 2016".Therapeutic Goods Administration (TGA).21 June 2022.Retrieved10 April2023.
- ^"Health Canada New Drug Authorizations: 2016 Highlights".Health Canada.14 March 2017.Retrieved7 April2024.
- ^ab"FDA working with manufacturers to withdraw Zinbryta from the market in the United States".U.S.Food and Drug Administration(FDA).Retrieved15 March2018.
- ^"Biogen, AbbVie withdraw multiple sclerosis drug Zinbryta".Reuters.2018.
- ^Loftus P (2 March 2018)."Biogen and Abbvie Take Multiple Sclerosis Drug Off Market".The Wall Street Journal.
- ^abFDA"BLA Approval letter"(PDF).U.S. Food and Drug Administration. 27 May 2016.
- ^abcLycke J (November 2015)."Monoclonal antibody therapies for the treatment of relapsing-remitting multiple sclerosis: differentiating mechanisms and clinical outcomes".Therapeutic Advances in Neurological Disorders.8(6): 274–293.doi:10.1177/1756285615605429.PMC4643868.PMID26600872.
- ^Liu J, Wang LN, Zhan S, Xia Y (December 2013). "Daclizumab for relapsing remitting multiple sclerosis".The Cochrane Database of Systematic Reviews(12): CD008127.doi:10.1002/14651858.CD008127.pub4.PMID24363032.
- ^"Rejection label Supplement label update"(PDF).U.S. Food and Drug Administration. September 2005.
- ^"EPAR for Zenapax"(PDF).European Medicines Agency. 2007.[permanent dead link]
- ^FDA Professional Drug Informationfor Zinbryta.
- ^abcdeHaberfeld, H, ed. (2016).Austria-Codex(in German). Vienna: Österreichischer Apothekerverlag.
- ^"Zinbryta Summary of Product Characteristics"(PDF).European Medicines Agency. 2016. Archived fromthe original(PDF)on 2018-06-14.Retrieved2016-12-09.
- ^"Zinbryta Article-20 referral - Summary of provisional measures"(PDF).European Medicines Agency. 20 July 2017. Archived fromthe original(PDF)on 24 July 2018.Retrieved21 July2017.
- ^"EMA review of Zinbryta confirms medicine's risks outweigh its benefits".European Medicines Agency.27 March 2018.
- ^Tsurushita N, Hinton PR, Kumar S (May 2005). "Design of humanized antibodies: from anti-Tac to Zenapax".Methods.36(1): 69–83.doi:10.1016/j.ymeth.2005.01.007.PMID15848076.
- ^abSwenson RS, Weisinger JR, Ruggeri JL, Reaven GM (February 1975). "Evidence that parathyroid hormone is not required for phosphate homeostasis in renal failure".Metabolism.24(2): 199–204.doi:10.1016/0026-0495(75)90021-9.PMID1113683.
- ^Fisher LM (12 December 1997)."Genetically Engineered Drug Approved for Kidney Transplants".The New York Times.
- ^ab"Roche's Zenapax Gets First Approval For Transplants".The Pharma Letter.17 December 1997.
- ^"Zenapax (daclizumab), The First Humanized Monoclonal Antibody To Prevent Organ Rejection, Approved In The European Union".Roche Press Release.4 March 1999. Archived fromthe originalon 28 August 2021.Retrieved1 June2016.
- ^Hoffmann C (16 September 2004)."Roche in new deal to co-development asthma drug".First Word Pharma.
- ^Thiel KA (October 2005). "A very firm handshake: biotech's growing negotiating power".Nature Biotechnology.23(10): 1221–1226.doi:10.1038/nbt1005-1221.PMID16211058.S2CID19365410.
- ^"Roche inks new deal for transplant drug".PharmaTimes.1 November 2005.
- ^"Roche ducks out of transplant drug alliance".PharmaTimes.23 November 2006.
- ^"EMEA: Withdrawal of the marketing authorisation in the European Union"(PDF).Archived fromthe original(PDF)on 2010-02-17.Retrieved2010-03-11.
- ^"Letter to Healthcare Professionals"(PDF).Roche.U.S. Food and Drug Administration. September 2009.
- ^Carroll J."Emerging Drug Developer: Facet Biotech".FierceBiotech.
- ^"PDL BioPharma, Inc. Form 8-K".17 December 2008.
- ^Timmerman L (4 September 2009)."Biogen Idec Makes Hostile $350M Takeover Bid for Facet Biotech".Xconomy.
- ^"Abbott to Buy Facet Biotech for 67% Premium".New York Times Dealbook.9 March 2010.
- ^"FDA approves Zinbryta to treat multiple sclerosis".FDA News Release.U.S. Food and Drug Administration. 27 May 2016.
- ^Sobrin L, Huang JJ, Christen W, Kafkala C, Choopong P, Foster CS (February 2008). "Daclizumab for treatment of birdshot chorioretinopathy".Archives of Ophthalmology.126(2): 186–191.doi:10.1001/archophthalmol.2007.49.PMID18268208.
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