Type of information: Granting of a Market Authorisation in the US
Product name: Inflectra™/Remsima™ (biosimilar version of infliximab (Remicade®))
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
- biosimilar/monoclonal antibody/TNF alpha inhibitor. Inflectra® (infliximab) is a biosimilar medicine to the reference medicinal product, Remicade® (infliximab), which was originally licensed in 1998. This is the first monoclonal antibody therapy to reach a positive opinion following review via the EMA biosimilars regulatory pathway. Inflectra® specifically targets tumour necrosis factor (TNF) alpha.
- In 2009, Hospira entered into an agreement with South Korean-based biopharmaceutical company, Celltrion, which is developing eight monoclonal antibody biosimilars. Under the terms of the agreement, Hospira obtained the rights to Inflectra® in Europe, the United States, Canada, Australia and New Zealand. Inflectra® is manufactured by Celltrion, based in Yeonsu-gu, Incheon, Republic of Korea, for Hospira, now Pfizer.
Company: Hospira (USA - IL) Celltrion (South Korea)
- inflammatory conditions including: rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriatic arthritis, psoriasis, rheumatoid arthritis
- • On April 5, 2016, the FDA approved Inflectra® (infliximab) for multiple indications. This is the second biosimilar approved by the FDA. Inflectra is approved for the treatment of:
- - adult patients and pediatric patients (ages six years and older) with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy;
- - adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy;
- - patients with moderately to severely active rheumatoid arthritis in combination with methotrexate;
- - patients with active ankylosing spondylitis (arthritis of the spine);
- - patients with active psoriatic arthritis;
- - adult patients with chronic severe plaque psoriasis.
- 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.
- The most common expected side effects of Inflectra® include respiratory infections, such as sinus infections and sore throat, headache, coughing and stomach 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.
- • On August 21, 2015, the PBAC recommended that Inflectra™ (infliximab), the first monoclonal antibody ‘mAb’ biosimilar registered in Australia, be added to the Pharmaceutical Benefits Scheme (PBS).
- • On August 20, 2015, Hospira announced that Inflectra™ (infliximab) has been registered in Australia. The drug has been registered in Australia for the treatment of eight inflammatory conditions (rheumatoid arthritis; psoriatic arthritis; ankylosing spondylitis ; adult and paediatric Crohn's disease; refractory fistulising Crohn’s disease; adult and paediatric ulcerative colitis; and plaque psoriasis). The approval is based on extensive data, including the results of pivotal trials in patients with rheumatoid arthritis and ankylosing spondylitiswhich concluded that the biosimilar was therapeutically comparable to Remicade®.
- • On April 27, 2015, The Brazilian Health Agency announced that it has approved Remsima® (infliximab) for the treatment of ankylosing spondylitis, colitis, ulcerative colitis, Crohn's disease, psoriatic arthritis, psoriasis and rheumatoid arthritis. The medication will be marketed by Hospira. The product has been approved in Brazil for the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, Crohn's disease in adults and children, fistulizing Crohn's disease (advanced), colitis and ulcerative rectocolitis. Remsima™ is the first biological medication approved by Brazil's regulator, ANVISA, based on comparability. A comparability study is required because under ANVISA's Normative Resolution RDC 55/2010, biosimilarity must be proven by direct comparison with the reference biological drug (products must be compared in a single clinical trial and using the same procedures). In a phase III trial involving 606 patients, Remsima™ achieved its main goal of treatment equivalence with Remicade. The trial showed that 73.4 percent of patients receiving Remsima™ achieved a 20 percent or better improvement in rheumatoid arthritis symptoms (based on American College of Rheumatology criteria) after 30 weeks of treatment, compared with 69.7 percent for Remicade™. During the same trial, 42.3 percent of patients receiving Remsima achieved a 50 percent or better improvement in rheumatoid arthritis symptoms (based on American College of Rheumatology criteria) after 30 weeks of treatment, compared with 40.6 percent for Remicade™. Remsima™ also presents a similar safety and tolerance profile to Remicade™.
- • On March 30, 2015, Hospira announces the availability of Inflectra™ (infliximab) in Canada, the country's first subsequent entry biologic (SEB - also referred to as a 'biosimilar' outside of Canada) monoclonal antibody (mAb) therapy. Approved by Health Canada, Inflectra™ is available to healthcare practitioners for the treatment of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis.
- • On February 16, 2015, Hospira announced the launch of Inflectra® (infliximab), in major European markets, including Austria, Denmark, France, Germany, Greece, Italy, Luxembourg, Netherlands, Spain and Sweden. Inflectra® is the first biosimilar mAb to be approved by the European Commission. Inflectra® is being launched in several major European markets, including Austria, Denmark, France, Germany, Greece, Italy, Luxembourg, Netherlands, Spain and Sweden. With the launch of the product in these new markets, Inflectra is now available in 24 European countries.
- • On August 11, 2014, Celltrion announced that the company, on August 8, 2014, completed the filing procedure to obtain US FDA approval for its infliximab biosimilar. This marks the first 351(k) biosimilar mAb application to be filed in the U.S.A. and the second application for a biosimilar to be filed through the US BPCIA. After prior consultation with the FDA, Celltrion conducted additional clinical trials (starting on October 2013 and lasting 6 months) to determine the bioequivalency of the originator products with Remsima®. Specifically, Celltrion tested for Pharmacokinetic/ Pharmacodynamic (PK/PD) equivalency and safety equivalency for the three distinct products, the originator products sold in the US, the originator products sold in Europe, and Remsima®. These additional clinical trial data, along with Celltrion's established global clinical trial data, were submitted to the FDA by Celltrion as part of its application. The patent for the originator drug is set to expire at the end of 2018 however, in support of its FDA application, Celltrion has currently filed a lawsuit in the federal court of Massachusetts seeking a declaratory judgment that Janssen Biotech's remaining patents on the original reference drug Remicade® (infliximab) are invalid and unenforceable.
• On July 16, 2014, Celltrion announced that the Ministry of Health in Turkey (MoH) has granted marketing approval for Remsima® (infliximab). Celltrion has received approval from the MoH for all applied indications, which are for the treatment of rheumatoid arthritis, ankylosing spondilitis, Crohn’s disease, ulcerative colitis, psoriasis and psoriatic arthritis.Last April 9th of 2013, Celltrion completed and submitted the application for Remsima® approval to the Turkish Medicines and Medical Devices Agency and after one year and three months, Celltrion received official approval from the MoH. Remsima® will be launched into the Turkish market beginning in the fourth quarter of this year, after administrative procedures are taken care of. Celltrion will be marketing Remsima® in Turkey through its partner company MN Pharmaceuticals (Mustafa Nevzat Pharmaceuticals), an Amgen's company.
• On July 4, 2014, Celltrion announced that the company has received marketing authorization for Remsima® (infliximab) from the Japan's Ministry of Health, Labour and Welfare (MHLW). With this latest marketing authorization in Japan, excluding the USA, Remsima® has now received approval from the majority of advanced nations (such as Europe and Canada) by passing regulations imposed by said nations and these approvals effectively open up for sales half of the entire market for Remsima’s originator drug infliximab. Celltrion anticipates submitting marketing authorization approval for Remsima® in the USA in the latter half of this year.
- • On February 13, 2014, Alvogen has announced the launch of Inflectra™ (Infliximab) into Central and Eastern Europe. Alvogen and Hospira formed a strategic partnership in 2011 to provide the highest quality products and services for customers and patients throughout Central and Eastern Europe. Alvogen will market the product in Bulgaria, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, and Romania.
- • On September 10, 2013, Hospira has announced the European Commission approval of Inflectra™ (infliximab), Europe's first biosimilar monoclonal antibody (mAb) therapy. Inflectra has been approved for the treatment of inflammatory conditions including rheumatoid arthritis (RA), ankylosing spondylitis, Crohn's disease (CD), ulcerative colitis (UC), psoriatic arthritis (PsA) and psoriasis. This biosimilar medicine to the reference medicinal product, Johnson&Johnson's Remicade® is the first monoclonal antibody to be approved through the European Medicines Agency (EMA) biosimilars regulatory pathway. Remicade® recorded European sales of over $ 2 billion in 2012. The introduction of biosimilar mAbs in Europe is expected to deliver savings of up to €20.4 billion by 2020, with the biggest savings predicted in France, Germany and the UK, according to Haustein et al. Inflectra™ will be launched throughout Europe at the earliest opportunity taking into account any relevant patent protection.
- • On June 27, 2013, the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending the granting of a marketing authorisation for Inflectra®(infliximab) for rheumatoid arthritis, inflammatory bowel disease and plaque psoriasis. The drug's safety, efficacy and tolerability have been established through a comprehensive clinical trial programme. In a phase III randomised, double-blind study, Inflectra® met its primary endpoint of therapeutic equivalence to the reference product. In the study, 73.4% of patients receiving Inflectra achieved a greater than 20% improvement in RA symptoms after 30 weeks of treatment (using the ACR20 scoring system), compared with 69.7% treated with reference infliximab. The safety and tolerability of Inflectra was also demonstrated to be comparable to Remicade®, supporting its approval.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2016-04-05
UE authorization: 2013-09-10
Favourable opinion UE: 2013-06-27
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
- Celltrion Healthcare has established a vast distribution network of partners and experts who have in-depth knowledge and experience in their local markets. In European markets, Celltrion Healthcare is in partnership with the following companies: Astro Pharma (Austria), Biogaran (France and Monaco), DEMO S.A.(Cyprus), Egis (Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Moldova, Bulgaria, Czech Republic, Latvia, Lithuania, Poland, Romania, Slovakia, Russia, Ukraine, Uzbekistan and Hungary), Hospira (Europe), Kern Pharma (Spain), Medical Logistics (Malta), Mundipharma (Belgium, Germany, Italy, Luxembourg, the Netherlands and the UK), Oktal Pharma (Slovenia, Croatia, Bosnia-Herzegovina and Serbia), Orion (Denmark, Estonia, Finland, Norway, and Sweden), PharmaKern (Portugal) and Pinewood (Ireland).