Simponi, Simponi Aria (golimumab) - 5 indications

Scroll down for information on each indication:

Simponi

• rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis; approved April 2009
• ulcerative colitis; approved May 2013

Simponi Aria

• rheumatoid arthritis;  approved July 2013
• psoriatic arthritis and ankylosing spondylitis; approved October 2017
• Active Polyarticular Juvenile Idiopathic Arthritis; approved September 2020

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).

Simponi is the subcutaneous formulation of golimumab and is specifically indicated for the following:

• for use in combination with methotrexate for the treatment of adult patients with moderately to severely active rheumatoid arthritis.
• for use alone or in combination with methotrexate for the treatment of adult patients with active psoriatic arthritis.
• for the treatment of adult patients with active ankylosing spondylitis.
• for adult patients with moderately to severely active ulcerative colitis who have demonstrated corticosteroid dependence or who have had an inadequate response to or failed to tolerate oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurin for:
  • inducing and maintaining clinical response
  • improving endoscopic appearance of the mucosa during induction
  • inducing clinical remission
  • achieving and sustaining clinical remission in induction responders

Simponi Aria is the intravenous infusion formulation of golimumab and is specifically indicated for: 

• use in combination with methotrexate for the treatment of adult patients with moderately to severely active rheumatoid arthritis
• for the treatment of active psoriatic arthritis in patients 2 years of age and older
• for the treatment of adult patients with active ankylosing spondylitis
• for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older

Simponi is supplied as a solution for subcutaneous injection. Simponi Arial is supplied as a solution for intravenous injection. Scroll down for the recommended dosing/administration for each indication and formulation.

Mechanism of Action

Golimumab is a human monoclonal antibody that binds to both the soluble and transmembrane bioactive forms of human TNFα. This interaction prevents the binding of TNFα to its receptors, thereby inhibiting the biological activity of TNFα (a cytokine protein). There was no evidence of the golimumab antibody binding to other TNF superfamily ligands; in particular, the golimumab antibody did not bind or neutralize human lymphotoxin. Golimumab did not lyse human monocytes expressing transmembrane TNF in the presence of complement or effector cells. Elevated TNFα levels in the blood, synovium, and joints have been implicated in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. TNFα is an important mediator of the articular inflammation that is characteristic of these diseases. The exact mechanism by which golimumab treats ulcerative colitis is unknown.

Side Effects

Adverse effects associated associated with the use of Simponi may include, but are not limited to, the following:

• upper respiratory tract infection
• nasopharyngitis
• injection site reactions

Adverse effects associated with the use of Simponi Aria may include, but are not limited to, the following:

• upper respiratory tract infection
• alanine aminotransferase increased
• viral infection
• aspartate aminotransferase increased
• neutrophil count decreased
• bronchitis
• hypertension
• rash

The Simponi/Simponi Aria drug label comes with the following Black Box Warning: SERIOUS INFECTIONS AND MALIGNANCY See full prescribing information for complete boxed warning. Serious infections leading to hospitalization or death including tuberculosis (TB), bacterial sepsis, invasive fungal (such as histoplasmosis), and other opportunistic infections have occurred in patients receiving Simponi/Simponi Aria. Discontinue Simponi/Simponi Aria if a patient develops a serious infection or sepsis. Perform test for latent TB; if positive, start treatment for TB prior to starting Simponi/Simponi Aria. Monitor all patients for active TB during treatment, even if initial latent TB test is negative. Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which Simponi/Simponi Aria is a member.

Indications 1, 2 and 3 - rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

Simponi: approved April 2009

Simponi Aria: approved July 2013 (RA); approved October 2017 (PA and AS)

Dosing/Administration

Simponi: 

• 50 mg administered by subcutaneous injection once a month

Simponi Aria: 

• 2 mg/kg intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter

Clinical Trial Results

Simponi

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. 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. 

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. 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. 

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 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. 

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.

Simponi Aria

The FDA approval of Simponi Aria for rheumatoid arthritis was based on one multicenter, randomized, double-blind, controlled trial in 592 patients ≥ 18 years of age with moderately to severely active RA despite concurrent MTX therapy and had not previously been treated with a biologic TNF-blocker. Patients were randomized to receive either Simponi Aria 2 mg/kg (N=395) or placebo (N=197) over a 30-minute intravenous infusion at Weeks 0, 4 and every 8 weeks thereafter in addition to their weekly maintenance MTX dose (15-25 mg). All patients receiving placebo + MTX received Simponi Aria + MTX after Week 24, but the trial remained blinded until all patients had completed 108 weeks of treatment. The primary endpoint in Trial RA was the percentage of patients achieving an ACR 20 response at Week 14. A greater percentage of patients treated with the combination of Simponi Aria + MTX achieved ACR 20 at Week 14 versus patients treated with the placebo + MTX (59% versus 25%, respectively).

The FDA approval of Simponi Aria for psoriatic arthritis was based on a multicenter, randomized, double-blind, placebo-controlled trial in 480 patients ≥ 18 years of age with active psoriatic arthritis despite NSAID or DMARD therapy. Patients were randomized to either receive Simponi Aria 2 mg/kg (N=241) or placebo (N=239) as a 30-minute intravenous infusion at Weeks 0, 4, 12 and 20. All patients on placebo received Simponi Aria at Week 24, Week 28 and every 8 weeks thereafter through Week 52. Patients in the Simponi Aria treatment group continued to receive Simponi Aria infusions at Week 28 and every 8 weeks through Week 52. The primary endpoint was the percentage of patients achieving an ACR 20 response at Week 14. Simponi Aria treatment, compared with placebo, resulted in a significant improvement in signs and symptoms as demonstrated by the percentage of patients with an ACR 20 response at Week 14 (75% versus 22%, respectively). 

The FDA approval of Simponi Aria for Ankylosing Spondylitis was based on a multicenter, randomized, double-blind, placebo-controlled trial in 208 patients ≥ 18 years of age with active ankylosing spondylitis (AS) and inadequate response or intolerance to NSAIDs. Patients were randomized to receive either Simponi Aria 2 mg/kg (N=105) or placebo (N=103) as a 30-minute intravenous infusion at Weeks 0, 4 and 12. All patients on placebo received Simponi Aria at Week 16, Week 20 and every 8 weeks thereafter through Week 52. Patients in the Simponi Aria treatment group continued to receive Simponi Aria infusions at Week 20 and every 8 weeks through Week 52. The primary endpoint was the percentage of patients achieving an Assessment in Ankylosing Spondylitis (ASAS) 20 response at Week 16. Simponi Aria treatment, compared with placebo, resulted in a significant improvement in signs and symptoms as demonstrated by the percentage of patients with an ASAS 20 response at Week 16 (73% versus 26%, respectively). 

Indication 4 - Ulcerative Colitis

approved May 2013

Dosing/Administration

The recommended dose is 200 mg initially administered by subcutaneous injection at Week 0, followed by 100 mg at Week 2 and then 100 mg every 4 weeks

Clinical Trial Results

The FDA approval of Simponi for ulcerative colitis was based on on two multi-center, randomized, double blind, placebo-controlled clinical trials in patients > 18 years of age (Trials UC-1 and UC-2).

Trial UC-1

• This was an induction trial conducted in patients with moderately to severely active ulcerative colitis (UC), defined as a Mayo score of 6 to 12, who were corticosteroid dependent and who had failed or were intolerant to prior therapies. This trial was conducted in two parts. In Part 1 (dose finding), patients were randomized to one of 4 treatment groups: 400 mg Simponi administered subcutaneously (SC) at Week 0 and 200 mg at Week 2 (400/200 mg), 200 mg Simponi SC at Week 0 and 100 mg at Week 2 (200/100 mg), 100 mg Simponi SC at Week 0 and 50 mg at Week 2 (100/50 mg), or placebo SC at Weeks 0 and 2. In Part 2 (dose confirming), 771 patients were randomized to receive either 400 mg Simponi SC at Week 0 and 200 mg at Week 2, 200 mg Simponi SC at Week 0 and 100 mg at Week 2, or placebo SC at Weeks 0 and 2. Simponi 100/50 mg SC was not evaluated in Part 2; its safety and effectiveness has not been established in UC. Concomitant stable doses of other therapies were allowed. A greater proportion of patients achieved clinical response, clinical remission and had improvement of endoscopic appearance of the mucosa at Week 6 in the Simponi 200/100 mg group compared with the placebo group. The Simponi 400/200 mg group did not demonstrate additional clinical benefit over the 200/100 mg group.

Trial UC-2

• This was a randomized-withdrawal maintenance trial that evaluated 463 patients who achieved clinical response with Simponi induction and tolerated Simponi treatment. Patients were randomized to receive Simponi 50 mg, Simponi 100 mg or placebo administered subcutaneously every 4 weeks. Concomitant stable doses of other therapies were allowed. The primary endpoint was the percent of patients maintaining clinical response through Week 54. A greater proportion of patients maintained clinical response through Week 54 in the Simponi 100 mg group compared with the placebo group. Simponi treated patients in clinical response (which included the subset of patients in clinical remission) in Trial UC-1, were again assessed for clinical remission at Week 30 and Week 54. A greater proportion of patients had clinical remission at both Weeks 30 and 54 without demonstrating a loss of response at any time point through Week 54 in the Simponi 100 mg group compared with the placebo group.

Indication 5 - Active Polyarticular Juvenile Idiopathic Arthritis

approved September 2020

Dosing/Administration

The Simponi Aria dosage regimen, based on body surface area (BSA), is 80 mg/m2 given as an intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.

Clinical Trial Results

The FDA approval of Simponi Aria was based on results from the GO-VIVA Phase 3 clinical trial, an open-label study in children with JIA with active polyarthritis ages 2 to 17 years who had active arthritis in five or more joints, despite receiving treatment with methotrexate for at least two months. Trial results demonstrated that pharmacokinetic (PK) exposure of Simponi Aria was consistent with that of two pivotal Phase 3 clinical trials of Simponi Aria in adult patients with moderately to severely active RA and active PsA. Efficacy was assessed as supportive endpoints through Week 52. The efficacy was generally consistent with responses in adult patients with RA.