Infliximab Biosimilar- Inflectra approved by FDA.

inflectraThe U.S. Food and Drug Administration today approved Inflectra (infliximab-dyyb) for multiple indications. Inflectra is administered by intravenous infusion.

INFLECTRA is now the first and only biosimilar monoclonal antibody (mAb) therapy, and only the second biosimilar, to be approved in the U.S.

A biosimilar product is a biological product that is approved based on a showing that it is highly similar to an already-approved biological product, known as a reference product. The biosimilar also must show it has no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products.

A biosimilar product can only be approved by the FDA if it has the same mechanism(s) of action (but only to the extent that the mechanism(s) of action are known for the reference product), route(s) of administration, dosage form(s) and strength(s) as the reference product, and only for the indication(s) and condition(s) of use that have been approved for the reference product. The facilities where biosimilars are manufactured must also meet the FDA’s standards.

The FDA’s approval of Inflectra is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Inflectra is biosimilar to Remicade. Inflectra has been approved as biosimilar, not as an interchangeable product.


Infliximab-dyyb, the active ingredient in INFLECTRA, is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions) specific for human tumor necrosis factor-alpha (TNFα).

It has a molecular weight of approximately 149.1 kilodaltons.

Infliximab-dyyb 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.


Mechanism of Action

  • Infliximab products neutralize the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα and inhibit binding of TNFα with its receptors.
  • Infliximab products do not neutralize TNFβ (lymphotoxin-α), a related cytokine that utilizes thesame receptors as TNFα.
  • Biological activities attributed to TNFα include:
    • induction of proinflammatory cytokines such as IL-1 and IL-6,
    • enhancement of leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes,
    • activation of neutrophil and eosinophil functional activity,
    • induction of acute phase reactants and other liver proteins, as well as tissue degrading enzymes produced by synoviocytes and/or chondrocytes.
  • Cells expressing transmembrane TNFα bound by infliximab products can be lysed in vitro or in vivo.
  • Infliximab products inhibit the functional activity of TNFα in a wide variety of in vitro bioassays utilizing human fibroblasts, endothelial cells, neutrophils, B and T lymphocytes and epithelial cells.
  • The relationship of these biological response markers to the mechanism(s) by which infliximab products exert their clinical effects is unknown.
  • Anti-TNFα antibodies reduce disease activity in the cotton-top tamarin colitis model, and decrease synovitis and joint erosions in a murine model of collagen-induced arthritis.
  • Infliximab products prevent disease in transgenic mice that develop polyarthritis as a result of constitutive expression of human TNFα, and when administered after disease onset, allows eroded joints to heal.


Inflectra is biosimilar to Janssen Biotech, Inc.’s Remicade (infliximab), which was originally licensed in 1998. Inflectra is indicated for:

  • Crohn’s Disease: Reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. Reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease.
  • Pediatric Crohn’s Disease: • reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy.
  • Ulcerative Colitis: reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.
  • Rheumatoid Arthritis in combination with methotrexate:  reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active disease.
  • Ankylosing Spondylitis: reducing signs and symptoms in patients with active disease.
  • Psoriatic Arthritis: reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function.
  • Plaque Psoriasis:  treatment of adult patients with chronic severe (i.e., extensive and /or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate.


  • INFLECTRA is administered by intravenous infusion over a period of not less than 2 hours.
  • Crohn’s Disease:  5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. Some adult patients who initially respond to treatment may benefit from increasing the dose to 10 mg/kg if they later lose their response.
  • Pediatric Crohn’s Disease: 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.
  • Ulcerative Colitis: 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.
  • Rheumatoid Arthritis: In conjunction with methotrexate, 3 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. Some patients may benefit from increasing the dose up to 10 mg/kg or treating as often as every 4 weeks.
  • Ankylosing Spondylitis  5 mg/kg at 0, 2 and 6 weeks, then every 6 weeks.
  • Psoriatic Arthritis and Plaque Psoriasis 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.


  • For injection: 100 mg of lyophilized infliximab-dyyb in a 20 mL vial for intravenous infusion.


  • INFLECTRA doses >5 mg/kg in moderate to severe heart failure.
  • Previous severe hypersensitivity reaction to infliximab products, or known hypersensitivity to inactive components of INFLECTRA or to any murine proteins.


  • Serious infections – do not give INFLECTRA during an active infection. If an infection develops, monitor carefully and stop INFLECTRA if infection becomes serious.
  • Invasive fungal infections – for patients who develop a systemic illness on INFLECTRA, consider empiric antifungal therapy for those who reside or travel to regions where mycoses are endemic
  • Malignancies – the incidence of malignancies including lymphoma was greater in TNF blocker treated patients than in controls. Due to the risk of HSTCL carefully assess the risk/benefit especially if the patient has Crohn’s disease or ulcerative colitis, is male, and is receiving azathioprine or 6­ mercaptopurine treatment.
  • Hepatitis B virus (HBV) reactivation – test for HBV infection before starting INFLECTRA. Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop INFLECTRA and begin anti-viral therapy.
  • Hepatotoxicity – rare severe hepatic reactions, some fatal or necessitating liver transplantation. Stop INFLECTRA in cases of jaundice and/or marked liver enzyme elevations.
  • Heart failure –new onset or worsening symptoms may occur. (4, 5.5)  Cytopenias – advise patients to seek immediate medical attention if signs and symptoms develop, and consider stopping INFLECTRA.
  • Hypersensitivity – serious infusion reactions including anaphylaxis or serum sickness-like reactions may occur.
  • Demyelinating disease –exacerbation or new onset may occur.
  • Lupus-like syndrome – stop INFLECTRA if syndrome develops.
  • Live vaccines or therapeutic infectious agents – should not be given with INFLECTRA. Bring pediatric patients up to date with all vaccinations prior to initiating INFLECTRA. At least a six month waiting period following birth is recommended before the administration of live vaccines to infants exposed in utero to infliximab products


  • Most common adverse reactions (>10%) – infections (e.g. upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.
  • Infusion reactions can happen up to two hours after an infusion. Symptoms of infusion reactions may include fever, chills, chest pain, low blood pressure or high blood pressure, shortness of breath, rash and itching.
  • Inflectra contains a Boxed Warning to alert health care professionals and patients about an increased risk of serious infections leading to hospitalization or death, including tuberculosis, bacterial sepsis, invasive fungal infections (such as histoplasmosis) and others.
  • The Boxed Warning also notes that lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including infliximab products such as Inflectra.
  • Other serious side effects may include liver injury, blood problems, lupus-like syndrome, psoriasis, and in rare cases nervous system disorders.
  • The drug must be dispensed with a patient Medication Guide that describes important information about its uses and risks.

Inflectra is manufactured by Celltrion, Inc, based in Yeonsu-gu, Incheon, Republic of Korea, for Hospira, of Lake Forest, Illinois. Remicade is marketed by Janssen Biotech, Inc., based in Horsham, Pennsylvania.

Hospira, now a Pfizer company, entered into an agreement with Celltrion Inc. and Celltrion Healthcare, Co., Ltd. in 2009 for several potential biosimilar products, including INFLECTRA. Pfizer holds exclusive commercialization rights to INFLECTRA in the U.S. and certain other jurisdictions.


Prescribing Label