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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_UK = POM
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = Investigational
| legal_status =
| routes_of_administration = [[Subcutaneous injection]]
| routes_of_administration = [[Subcutaneous injection]]
| licence_EU = Stelara
}}
}}
'''Ustekinumab''' ([[International Nonproprietary Name|INN]], experimental name '''CNTO 1275''', proprietary commercial name '''Stelara''',<ref>European Medicines Agency, 20 November 2008,http://www.emea.europa.eu/pdfs/human/opinion/Stelara_58227008en.pdf </ref> is a human [[monoclonal antibody]] developed by the biotechnology company [[Centocor]]. It is a laboratory-manufactured [[Monoclonal antibodies|monoclonal antibody]] directed against [[interleukin]]s [[Interleukin 12|IL-12]] and [[Interleukin 23|IL-23]], naturally occurring proteins that are important in regulating the immune system and that are also believed to play a role in immune-mediated inflammatory disorders.<ref name="pmid17761156">{{cite journal |author=Reddy M, Davis C, Wong J, Marsters P, Pendley C, Prabhakar U |title=Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275 |journal=Cell. Immunol. |volume=247 |issue=1 |pages=1–11 |year=2007 |month=May |pmid=17761156 |doi=10.1016/j.cellimm.2007.06.006 |url=http://linkinghub.elsevier.com/retrieve/pii/S0008-8749(07)00149-9}}</ref> Ustekinumab is presently undergoing [[clinical trial]]s to determine its safety and effectiveness against [[multiple sclerosis]], [[psoriasis]], and [[psoriatic arthritis]]. The results of [[clinical trial#Phase III|Phase III]] trials for psoriasis have been encouraging; two large [[randomized controlled trial]]s, one conducted over 76 weeks and the other over a year, showed ustekinumab to be safe and effective for moderate to severe psoriasis.<ref name=PHOENIX1>{{cite journal |author=Leonardi CL, Kimball AB, Papp KA, ''et al'' |title=Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1) |journal=Lancet |volume=371 |issue=9625 |pages=1665–74 |year=2008 |month=May |pmid=18486739 |doi=10.1016/S0140-6736(08)60725-4 |url=}}</ref><ref name=PHOENIX2>{{cite journal |author=Papp KA, Langley RG, Lebwohl M, ''et al'' |title=Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2) |journal=Lancet |volume=371 |issue=9625 |pages=1675–84 |year=2008 |month=May |pmid=18486740 |doi=10.1016/S0140-6736(08)60726-6 |url=}}</ref> Ustekinumab is approved in Canada and Europe to treat moderate to severe plaque psoriasis and is currently under review in the United States.<ref>[http://news.idsk.com/viewer/story.php?CLIENT=INFOMAILER&NEWSID=prn121520081223240607 Medarex to Receive Milestone Payment for Approval of STELARA(TM) (Ustekinumab) for the Treatment of Moderate to Severe Plaque Psoriasis]</ref>
'''Ustekinumab''' ([[International Nonproprietary Name|INN]], experimental name '''CNTO 1275''', proprietary commercial name '''Stelara''',<ref>European Medicines Agency, 20 November 2008,http://www.emea.europa.eu/pdfs/human/opinion/Stelara_58227008en.pdf </ref> is a human [[monoclonal antibody]] developed by the biotechnology company [[Centocor]]. It is a laboratory-manufactured [[Monoclonal antibodies|monoclonal antibody]] directed against [[interleukin]]s [[Interleukin 12|IL-12]] and [[Interleukin 23|IL-23]], naturally occurring proteins that are important in regulating the immune system and that are also believed to play a role in immune-mediated inflammatory disorders.<ref name="pmid17761156">{{cite journal |author=Reddy M, Davis C, Wong J, Marsters P, Pendley C, Prabhakar U |title=Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275 |journal=Cell. Immunol. |volume=247 |issue=1 |pages=1–11 |year=2007 |month=May |pmid=17761156 |doi=10.1016/j.cellimm.2007.06.006 |url=http://linkinghub.elsevier.com/retrieve/pii/S0008-8749(07)00149-9}}</ref> Ustekinumab is presently undergoing [[clinical trial]]s to determine its safety and effectiveness against [[multiple sclerosis]], [[psoriasis]], and [[psoriatic arthritis]]. The results of [[clinical trial#Phase III|Phase III]] trials for psoriasis have been encouraging; two large [[randomized controlled trial]]s, one conducted over 76 weeks and the other over a year, showed ustekinumab to be safe and effective for moderate to severe psoriasis.<ref name=PHOENIX1>{{cite journal |author=Leonardi CL, Kimball AB, Papp KA, ''et al'' |title=Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1) |journal=Lancet |volume=371 |issue=9625 |pages=1665–74 |year=2008 |month=May |pmid=18486739 |doi=10.1016/S0140-6736(08)60725-4 |url=}}</ref><ref name=PHOENIX2>{{cite journal |author=Papp KA, Langley RG, Lebwohl M, ''et al'' |title=Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2) |journal=Lancet |volume=371 |issue=9625 |pages=1675–84 |year=2008 |month=May |pmid=18486740 |doi=10.1016/S0140-6736(08)60726-6 |url=}}</ref> Ustekinumab is approved in Canada and Europe to treat moderate to severe plaque psoriasis and is currently under review in the United States.<ref>[http://news.idsk.com/viewer/story.php?CLIENT=INFOMAILER&NEWSID=prn121520081223240607 Medarex to Receive Milestone Payment for Approval of STELARA(TM) (Ustekinumab) for the Treatment of Moderate to Severe Plaque Psoriasis]</ref>

Revision as of 11:27, 28 April 2009

Ustekinumab
Monoclonal antibody
Type?
SourceHuman
TargetIL-12 and IL-23
Clinical data
License data
Routes of
administration		Subcutaneous injection
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
Identifiers
CAS Number
Chemical and physical data
FormulaC6482H10004N1712O2016S46
Molar mass145.64 kDa g·mol−1

Ustekinumab (INN, experimental name CNTO 1275, proprietary commercial name Stelara,[1] is a human monoclonal antibody developed by the biotechnology company Centocor. It is a laboratory-manufactured monoclonal antibody directed against interleukins IL-12 and IL-23, naturally occurring proteins that are important in regulating the immune system and that are also believed to play a role in immune-mediated inflammatory disorders.[2] Ustekinumab is presently undergoing clinical trials to determine its safety and effectiveness against multiple sclerosis, psoriasis, and psoriatic arthritis. The results of Phase III trials for psoriasis have been encouraging; two large randomized controlled trials, one conducted over 76 weeks and the other over a year, showed ustekinumab to be safe and effective for moderate to severe psoriasis.[3][4] Ustekinumab is approved in Canada and Europe to treat moderate to severe plaque psoriasis and is currently under review in the United States.[5]

Development

As of January 2007, there were 5 NIH-listed research studies involving CNTO 1275 on a multinational basis, including 3 Phase II and 2 Phase III trials. Three studies are focused on patients with psoriasis, one on psoriatic arthritis, and one on multiple sclerosis.

On December 4, 2007, a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) was filed by Centocor and Janssen-Cilag International (collaborator) has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA).

On June 17, 2008, the Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC) of the U.S. Food and Drug Administration unanimously recommended the approval of ustekinumab (CNTO 1275) for the treatment of adult patients with moderate to severe plaque psoriasis. The decision by the committee is non-binding and final decisions on approval of the drug are made by the FDA. As yet, there is no schedule for when the FDA will make a decision on CNTO 1275.

On November 21, 2008, the European Medicines Agency’s (EMEA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for ustekinumab for the treatment of moderate to severe plaque psoriasis in adult patients who failed to respond to other systemic therapies.[6]

On December 12, 2008 the Canadian Health Authority approved the use of ustekinumab for the treatment of chronic moderate to severe plaque psoriasis in adult patients who are candidates for phototherapy or systemic therapy.[7]

In September 2008, Centocor released result of a study comparing etanercept and ustekinumab. The entanercept group received subcutaneous injections of the drug twice weekly for 12-weeks while the ustekinumab group received 2 injections, one-month apart, of either 90 or 45 milligrams. At twelve weeks, psoriatic plaques were reduced by at least three-quarters in 68% of the low-dose ustekinumab group and 74% of the high-dose group. Both groups fared better than the etanercept group, 57% of whom saw such improvement. Dr. Alan Menter, chairman of psoriasis research at Baylor Research Institute said of the results, "now we have a drug that will be used less frequently ... with a significant increase in effectiveness. These results are as good as we've seen in psoriasis."[8]

Delivery

Patients enrolled in clinical trials of CNTO 1275 are scheduled to receive the drug by subcutaneous injections at doses of either 45 or 90 mg. The dosage and frequency varies by study and application (type of disease targeted). Generally the initial dosing interval is once per week followed by a step-down to once per month or even once every three months.

Mechanism of action

CNTO 1275 is designed to interfere with the triggering of the body's inflammatory response through the suppression of certain cytokines. Specifically, CNTO 1275 blocks interleukin IL-12 and IL-23 which help activiate certain T-cells.

References

  1. ^ European Medicines Agency, 20 November 2008,http://www.emea.europa.eu/pdfs/human/opinion/Stelara_58227008en.pdf
  2. ^ Reddy M, Davis C, Wong J, Marsters P, Pendley C, Prabhakar U (2007). "Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275". Cell. Immunol. 247 (1): 1–11. doi:10.1016/j.cellimm.2007.06.006. PMID 17761156. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Leonardi CL, Kimball AB, Papp KA; et al. (2008). "Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1)". Lancet. 371 (9625): 1665–74. doi:10.1016/S0140-6736(08)60725-4. PMID 18486739. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ Papp KA, Langley RG, Lebwohl M; et al. (2008). "Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2)". Lancet. 371 (9625): 1675–84. doi:10.1016/S0140-6736(08)60726-6. PMID 18486740. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Medarex to Receive Milestone Payment for Approval of STELARA(TM) (Ustekinumab) for the Treatment of Moderate to Severe Plaque Psoriasis
  6. ^ Centocor 12/19/08 Press Release, http://www.centocor.com/centocor/i/press_releases/FDA_ISSUES_COMPLETE_RESPONSE_LETTER_TO_CENTOCOR_FOR_USTEKINUMAB_BIOLOGIC_LICENSE_APPLICATION_
  7. ^ Centocor 12/19/08 Press Release, http://www.centocor.com/centocor/i/press_releases/FDA_ISSUES_COMPLETE_RESPONSE_LETTER_TO_CENTOCOR_FOR_USTEKINUMAB_BIOLOGIC_LICENSE_APPLICATION_
  8. ^ Johnson LL. "Study: Drug for serious psoriasis tops competition" The Associated Press. 18 Sept 2008.

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