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Home » Drug Information » FDA Approved Drugs » 2009
Medical Areas: Musculoskeletal | Rheumatology | Family Medicine

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Simponi (golimumab)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company: Centocor Ortho Biotech
Approval Status: Approved April 2009
Treatment Area: rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

General Information

Simponi (golimumab) is a human monoclonal antibody that binds to both the soluble and transmembrane bioactive forms of human TNFa. This interaction prevents the binding of TNFa to its receptors, thereby inhibiting the biological activity of TNFa (a cytokine protein).

The specific indications are as follows:
Rheumatoid Arthritis Simponi in combination with methotrexate, is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis.
Psoriatic Arthritis Simponi alone or in combination with methotrexate, is indicated for the treatment of adult patients with active psoriatic arthritis.
Ankylosing Spondylitis Simponi is indicated for the treatment of adult patients with active ankylosing spondylitis.

Simponi is supplied as a solution for subcutaneous injection. The recommended initial dose for all three indications is 50 mg administered by subcutaneous injection once a month.

Clinical Results

FDA Approval

The FDA approval of Simponi for rheumatoid arthritis was based on three multicenter, randomized, double-blind, controlled trials (Studies RA-1, RA-2, and RA-3).
Study RA-1
This multicenter, randomized, double-blind, controlled trial enrolled 461 patients who were previously treated (at least 8 to 12 weeks prior to administration of study agent) with one or more doses of a biologic TNF-blocker. The subjects were randomized to receive placebo, Simponi 50 mg or Simponi 100 mg, along with any current stable concomitant MTX, SSZ or HCQ. Simponi was administered subcutaneously every 4 weeks through Week 24. The primary endpoint was the percentage of patients achieving an ACR 20 response at Week 14. A greater percentage of patients treated with the combination of Simponi and MTX achieved ACR responses at Week 14 and Week 24 versus patients treated with the MTX alone. There was no clear evidence of improved ACR response with the higher Simponi dose group (100 mg) compared to the lower Simponi dose group (50 mg). In the subset of patients who received Simponi in combination with MTX, the proportion of patients achieving ACR 20, 50 and 70 responses at Week 14 were 40%, 18%, and 13%, respectively, in the Simponi 50 mg + MTX group compared with 17%, 6%, and 2%, respectively, in the placebo + MTX group. In addition, the Simponi 50 mg groups demonstrated a greater improvement compared to the control groups in the change in mean Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to Week 24: 0.25 vs. 0.05, respectively. The Simponi 50 mg groups also had a greater proportion of HAQ responders compared to the control groups at Week 24: 44% vs. 28%.
Study RA-2
This multicenter, randomized, double-blind, controlled trial enrolled 444 patients who had active RA despite a stable dose of at least 15 mg/week of MTX and who had not been previously treated with a biologic TNF-blocker. The subjects were randomized to receive background MTX, Simponi 50 mg + background MTX, Simponi 100 mg + background MTX or Simponi 100 mg monotherapy. Simponi was administered subcutaneously every 4 weeks through Week 24. The use of other DMARDs was prohibited. The primary endpoint was the percentage of patients achieving an ACR 20 response at Week 14. A greater percentage of patients treated with the combination of Simponi and MTX achieved ACR responses at Week 14 and Week 24.There was no clear evidence of improved ACR response with the higher Simponi dose group compared to the lower dose group. The Simponi monotherapy group was not statistically different from the MTX monotherapy group in ACR responses. The ACR20, ACR50 and ACR70 responses at Week 14 were 55%, 35% and 13% for the Simponi + MTX arm versus 33%, 10% and 4% in the MTX monotherapy arm. In addition, the Simponi 50 mg group demonstrated a greater improvement compared to the control group in the change in mean Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to Week 24: 0.47 vs. 0.13, respectively. The Simponi 50 mg group also had a greater proportion of HAQ responders compared to the control group: 65% vs. 35%, respectively.
Study RA-3
This multicenter, randomized, double-blind, controlled trial enrolled 637 patients with active RA who were MTX-naïve and had not previously been treated with a biologic TNF-blocker. The subjects received MTX, Simponi 50 mg + MTX, Simponi 100 mg + MTX, or Simponi 100 mg monotherapy). For patients receiving MTX, MTX was administered at a dose of 10 mg/week beginning at Week 0 and increased to 20 mg/week by Week 8. Simponi was administered subcutaneously every 4 weeks through Week 24. The use of other DMARD's was prohibited. The primary endpoint was the percentage of patients achieving an ACR 50 response at Week 24. A greater percentage of patients treated with the combination of Simponi and MTX achieved ACR responses at Week 24 compared with MTX alone. The Simponi monotherapy groups were not statistically different from the MTX monotherapy groups in ACR responses. The ACR20, ACR50 and ACR70 responses at Week 24 were 62%, 40% and 24% for the Simponi + MTX arm versus 49%, 29% and 16% for MTX alone.

The FDA approval of Simponi for Psoriatic Arthritis (PsA) was based on a multi-center, randomized, double-blind, placebo-controlled trial in 405 adults with moderately to severely active PsA despite NSAID or DMARD therapy. The subjects were randomly assigned to placebo, Simponi 50 mg or Simponi 100 mg given subcutaneously every 4 weeks. Patients were allowed to receive stable doses of concomitant MTX, low dose oral corticosteroids and/or NSAIDs during the trial. The primary endpoint was the percentage of patients achieving ACR 20 response at Week 14. There was no clear evidence of improved ACR response with the higher Simponi dose group compared to the lower Simponi dose group. The ACR20, ACR50 and ACR70 responses at Week 14 were 51%, 30% and 12% for the Simponi + MTX arm versus 9%, 2% and 1% for the placebo + MTX arm. In addition, Simponi 50 mg demonstrated a greater improvement compared to placebo in the change in mean Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to Week 24 (0.33 and -0.01, respectively). The Simponi 50 mg group also had a greater proportion of HAQ responders at Week 24 compared to the placebo group: 43% vs. 22%, respectively.

The FDA approval of Simponi for ankylosing spondylitis was based on a multi-center, randomized, double-blind, placebo-controlled trial in 356 adults with active disease. The subjects received placebo, Simponi 50 mg or Simponi 100 mg administered subcutaneously every 4 weeks. Patients were allowed to continue stable doses of concomitant MTX, SSZ, HCQ and/or NSAIDs during the trial. The primary endpoint was the percentage of patients achieving an ASsessment in Ankylosing Spondylitis (ASAS) 20 response at Week 14. Simponi + DMARDs treatment resulted in a significant improvement in signs and symptoms compared with placebo + DMARDs, as demonstrated by the proportion of patients with an ASAS 20 response at Week 14. The ASAS 20 and ASAS 40 responses at Week 14 were 59% and 45%, respectively, for Simponi + DMARDs versus 22% and 15%, resectively for placebo + DMARDs.

Ongoing Study Commitments

  • Centocor Ortho Biotech has agreed to assess the pharmacokinetics, safety, immunogenicity, and efficacy of golimumab in pediatric patients 2 to 16 years of age with active polyarticular juvenile idiopathic arthritis (pJIA).
    Protocol Submission: October 2009
    Trial Completion Date: June 2013
    Final Report Submission: October 2013

  • Side Effects

    Adverse events associated associated with the use of Simponi may include, but are not limited to, the following:
    • Upper respiratory tract infection
    • Nasopharyngitis
    • Alanine aminotransferase increased
    • Injection site erythema
    • Hypertension
    • Aspartate aminotransferase increased

    Mechanism of Action

    Simponi (golimumab) is a human IgG1k monoclonal antibody specific for human tumor necrosis factor alpha (TNFa). It was created using genetically engineered mice immunized with human TNF, resulting in an antibody with human-derived antibody variable and constant regions. Simponi is produced by a recombinant cell line cultured by continuous perfusion and is purified by a series of steps that includes measures to inactivate and remove viruses.

    Literature References

    Emery P, Fleischmann RM, Moreland LW, Hsia EC, Strusberg I, Durez P, Nash P, Amante EJ, Churchill M, Park W, Pons-Estel BA, Doyle MK, Visvanathan S, Xu W, Rahman MU Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis and Rheumatism 2009 Aug;60(8):2272-83

    Xu Z, Vu T, Lee H, Hu C, Ling J, Yan H, Baker D, Beutler A, Pendley C, Wagner C, Davis HM, Zhou H Population pharmacokinetics of golimumab, an anti-tumor necrosis factor-alpha human monoclonal antibody, in patients with psoriatic arthritis. Journal of Clinical Pharmacology 2009 Sep;49(9):1056-70

    Smolen JS, Kay J, Doyle MK, Landewé R, Matteson EL, Wollenhaupt J, Gaylis N, Murphy FT, Neal JS, Zhou Y, Visvanathan S, Hsia EC, Rahman MU; GO-AFTER study investigators Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet 2009 Jul 18;374(9685):210-21

    Kavanaugh A, McInnes I, Mease P, Krueger GG, Gladman D, Gomez-Reino J, Papp K, Zrubek J, Mudivarthy S, Mack M, Visvanathan S, Beutler A Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis and Rheumatism 2009 Apr;60(4):976-86

    Keystone EC, Genovese MC, Klareskog L, Hsia EC, Hall ST, Miranda PC, Pazdur J, Bae SC, Palmer W, Zrubek J, Wiekowski M, Visvanathan S, Wu Z, Rahman MU; GO-FORWARD Study Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Annals of the Rheumatic Diseases 2009 Jun;68(6):789-96

    Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, Mack M, Han J, Visvanathan S, Xu Z, Hsu B, Beutler A, Braun J Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis and Rheumatism 2008 Nov;58(11):3402-12

    Kay J, Matteson EL, Dasgupta B, Nash P, Durez P, Hall S, Hsia EC, Han J, Wagner C, Xu Z, Visvanathan S, Rahman MU Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study. Arthritis and Rheumatism 2008 Apr;58(4):964-75

    Additional Information

    For additional information regarding Simponi or rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, please visit the Simponi web page.