Simponi

Ashley Promhouse, Haley Drake, Nikita Fehr, Jungmin Lee, Meghan Lawson

Pharmacology

Take Home Points

• Simponi is a self-injectable human IgG monoclonal antibody

• Simponi is a self-injectable human IgG antibody acting as a TNF-alpha antagonist
• Used in the treatment of ulcerative colitis to induce clinical response, remission, mucosal healing, and increased quality of life
• Dosing: 200mg SC initially, then 100mg in 1 week, then 100mg q4w thereafer
• Expensive and not considered first line treatment

Mechanism of Action

Dosing

Administration &

Storage

Cost

• 200mg SC initially, then 100mg in 1 week, then 100mg every 4 weeks thereafter
• Store in refrigerator and bring dose to room temperature 30 minutes before injecting
• Inject into multiple different sites on thigh, lower abdomen, or upper arm

• Binds to the soluble and transmembrane forms of TNF-alpha to inhibit its biological activity
• Exact mechanism of action in Ulcerative Colitis is unknown

• Simponi® I.V. 4 mL vial: $876.86
• Pre-filled syringe and Autoinjector: $1570.21
• Does not meet criteria for EDS coverage

Dosage Forms

Indications:

• Moderate-severe active ulcerative colitis
• Active psoriatic arthritis
• Active ankylosing spondylitis
• Moderate-severe active rheumatoid arthritis

• SmartJect® autoinjector
• 50 mg/0.5 mL in a single dose
• 100 mg/1 mL in a single dose
• Pre-filled syringe
• 50 mg/0.5 mL in a single dose
• 100 mg/1 mL in a single dose
• Simponi® I.V.
• Supplied as a sterile solution for IV infusion in a 4 mL singe use vial

Efficacy

Safety

Drug-Drug Interactions

• Other biological therapeutics used to treat the same condition
• Live vaccines
• CYP450 substrates with a narrow therapeutic index (Warfarin, Theophylline)

Adverse Effects

Contraindications

• Major (>10%):
• Upper respiratory tract infection
• Miscellaneous infection

• Severe infections (sepsis, tuberculosis)
• Moderate or severe CHF
• Hypersensitivity to golimumab

• PURSUIT study compared 200mg/100mg Simponi, 400mg/200mg Simponi, and placebo doses
• Response rates were 51.0%, 54.9%, and 30.3% respectively
• Secondary endpoints of the study included clinical remission and mucosal healing which were significantly greater with Simponi than placebo

Rare (<1%):

• Congestive heart failure
• Anaphylaxis
• Sepsis
• Abscess
• Cellulitis
• Leukemia
• Tuberculosis

Minor (1%-10%):

• Hypertension
• Dizziness
• Skin rash
• Increased serum ALT
• Antibody development

Place in Therapy

Disease State: Ulcerative Colitis

Patient Case

• Simponi is not considered first line therapy for the treatment of ulcerative colitis
• Uses:
• inadequate response to prior treatment
• intolerance to prior treatment
• requirement for continuous steroid therapy

Disease State

Goals of Therapy

• Induce and maintain remission
• Prevent development of colon cancer
• Improve nutritional status
• Treat extraintestinal manifestations

• Autoimmune disease causing inflammation of the colonic mucosa
• One of two inflammatory bowel diseases (IBD) with the other being Crohn's disease
• Characterized by elevated TNF-alpha in the blood, synovium, and joints
• Chronic disease characterized by exacerbations and remissions
• Peak onset at ages 10-40 years old
• Cause unknown
• Risk factors include Jewish decent, family history of IBD, frequent NSAID use, and diet

Current Treatment Options

• aminosalicylates (5-ASA)
• corticosteroids
• immunosuppressives
• antidiarrheals
• analgesics
• surgery
• First line agents: Salofalk, Asacol, Pentasa (5-ASA)

Symptoms

• bloody diarrhea
• vomiting
• weight loss
• fever
• abdominal pain

Manufacturing Process

5) Manufacture

1) Development Genetics:

• Frozen, bulk substance is thawed, mixed, sterile filtered, and aseptically filled into 1 mL syringes

• Produced by a murine hybridoma cell line with recombinant DNA technology

4) Purification Process

2) Cell Bank System

• Affinity, cation, and anion exchange chromatography
• Viral inactivation
• Filtration

• 2-tiered system
• Seed cells were grown in a medium not containing fetal bovine serum

3) Fermentation Process

• Stage 1: pre-culture in seed bioreactor and expansion for larger volume
• Stage 2: bioreactor production and transfer of seed reactor contents