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Date: 2017-04-21

Type of information: Granting of a Market Authorisation in the US

Product name: Flixabi®/Renflexis® - SB2 - (Infliximab-abda - biosimilar version of infliximab (Remicade®)))

Compound: infliximab

Therapeutic area: Autoimmune diseases – Digestive diseases - Inflammatory diseases - Rheumatic diseases

Action mechanism: monoclonal antibody/biosimilar. SB2 is a biosimilar version of infliximab (reference biologic Remicade®). It is used to treat autoimmune diseases, including rheumatoid arthritis.

Company: Merck&Co (USA - NJ) Samsung Bioepis (Republic of Korea)

Disease: rheumatic arthritis, adult Crohn's disease, pediatric Crohn's disease, ulcerative colitis, pediatric ulcerative colitis, psoriatic arthritis, ankylosing spondylitis, psoriasis

Latest news:

  • • On April 21, 2017, the FDA approved Renflexis® (infliximab-abda) for multiple indications. Renflexis is administered by intravenous infusion. The  biosimilar product is manufactured by Samsung Bioepis for Merck&Co. Renflexis  is the second FDA-approved biosimilar to U.S.-licensed Remicade®. In April 2016, the FDA has already approved Inflectra® (infliximab) for multiple indications.
  • • On May 30, 2016, the European Commission granted marketing authorization in the European Union (EU) for Flixabi®, an infliximab biosimilar referencing Remicade®. Flixabi® is indicated for the treatment of adults with rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. Additionally, the drug can be used in patients 6 to 17 years old with severe, active Crohn’s disease or severely active ulcerative colitis. Flixabi® will be the second anti-TNF biosimilar to be manufactured and commercialized by Biogen in the EU. As part of the submission, Samsung Bioepis provided a preclinical and clinical data package from head-to-head Phase 1 and Phase 3 clinical trials comparing Flixabi® with the reference product Remicade®. A 54-week, double-blind, Phase 3 study was conducted in patients with moderate to severe rheumatoid arthritis  despite methotrexate therapy. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30 in the per-protocol set (PPS).vii The primary end point for the study was met, with data showing that patients taking Flixabi® had an equivalent ACR20 response and a comparable safety profile to those taking Remicade. The ACR20 response rate at week 30 in the PPS showed equivalence of Flixabi® to Remicade: 64.1% vs. 66.0%, respectively (adjusted difference ?1.88%; 95% CI: ?10.26% to 6.51%). The ACR20 response rate at week 54 in the PPS confirmed equivalent efficacy, with results showing 65.3% vs. 69.2%, respectively (adjusted difference 3.07%; 95% CI: ?12.00% to 5.86%). ACR20 response in the full analysis set at week 30 and week 54 also showed equivalence of Flixabi® to Remicade®: 55.5% vs. 59.0%, respectively (adjusted difference 2.95%; 95% CI: ?10.88% to 4.97%) at week 30 and 50.7% vs. 52.6%, respectively (adjusted difference 1.15%; 95% CI: ?9.16% to 6.86%) at week 54.
  • • On May 24, 2016, Samsung Bioepis announced that the FDA has accepted for review the company’s Biologics License Application (BLA) for SB2, a biosimilar candidate referencing Remicade® (infliximab), for the treatment of rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. SB2 is the first Samsung Bioepis biosimilar candidate submitted for review in the US. If approved, the marketing and distribution of SB2 in the US will be handled by Merck&Co, in accordance with a commercialization agreement signed in 2013. Samsung Bioepis’ BLA for SB2 was based on Phase 1 and Phase 3 clinical studies that tested the biosimilarity of SB2 to Remicade®. In a 54-week Phase 3 clinical study, SB2 showed comparable safety and equivalent efficacy to Remicade®, as evidenced in ACR20 response rate of 65.3% in the SB2 arm versus 69.2% in the Remicade® arm, fully supporting the 30-week study results of 64.1% and 66.0%, respectively. The SB2 study randomized 584 patients with moderate to severe rheumatoid arthritis despite methotrexate therapy across 73 sites in 11 countries.
  • • On 1 April 2016, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Flixabi® (previously known as SB2), intended for the treatment of rheumatoid arthritis, adult Crohn’s disease, paediatric Crohn’s disease, ulcerative colitis, paediatric ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and psoriasis. Flixabi® will be available as a 100 mg powder for concentrate for solution for infusion. This monoclonal antibody is a biological medicinal product similar to the reference product Remicade® (infliximab) authorised in the EU since 13 August 1999. Studies have shown Flixabi® to have comparable quality, safety and efficacy to Remicade® (infliximab). A  54-week, double-blind, Phase 3 study was conducted in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30 in the per-protocol set (PPS). The primary end point for the study was met, with data showing patients taking Flixabi® had an equivalent ACR20 response and a comparable safety profile to those taking Remicade®. A total of 584 patients were randomized in a 1:1 ratio to either Flixabi® (N=291, 290 analyzed) or Remicade® (N=293)iThe ACR20 response rate at week 30 in the PPS showed equivalence of Flixabi® to Remicade®: 64.1% vs. 66.0%, respectively. The ACR20 response rate at week 54 in the PPS confirmed equivalent efficacy, with results showing 65.3% vs. 69.2%, respectively (adjusted difference 3.07%; 95% CI: 12.00% to 5.86%) iv ACR20 response in the full analysis set at week 30 and week 54 also showed equivalence of Flixabi® to Remicade®: 55.5% vs. 59.0%, respectively (adjusted difference 2.95%; 95% CI: 10.88% to 4.97%) at week 30 and 50.7% vs. 52.6%, respectively (adjusted difference 1.15%; 95% CI: 9.16% to 6.86%) at week 54.
  • • On December 7, 2015, Merck&Co announced that Samsung Bioepis has received approval of Renflexis™ (infliximab), a biosimilar of Remicade®, by the Ministry of Food and Drug Safety (MFDS) in Korea. Merck&Co will commercialize Samsung Bioepis’ Renflexis™ in Korea as part of Merck’s commercialization partnership with Samsung Bioepis to offer high-quality biosimilar alternatives to existing biologic medicines.
Samsung Bioepis’ Renflexis™ is indicated in Korea for the treatment of rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, psoriatic arthritis and plaque psoriasis in adult patients (age 18 years and older). Merck&Co plans to launch Renflexis™ in South Korea in the first half of 2016. Merck&Co ’s commercial launch of Renflexis™ in Korea will include comprehensive education and support services for healthcare professionals, patients and their caregivers, including biosimilars education, disease education, and reimbursement and access support. • On March 13, 2015, Samsung Bioepis announced that the Marketing Authorization Application (MAA) for SB2, its Remicade (Infliximab) biosimilar candidate, has been submitted to the European Medicines Agency (EMA). This is the second biosimilar candidate MAA that Samsung Bioepis has submitted to the EMA. Last January, the MAA for its Enbrel® (etanercept) biosimilar candidate, SB4, has been validated and accepted for review by the EMA. The MAA is based on results from an extensive head-to-head preclinical data package comparing SB2 to the originator, a head-to-head Phase I study in healthy volunteers, and a head-to-head Phase III equivalence trial in patients with moderate-to-severe rheumatoid arthritis (RA). In Europe, Remicade® is indicated for the treatment of rheumatic arthritis, adult Crohn's disease, pediatric Crohn's disease, ulcerative colitis, pediatric ulcerative colitis, psoriatic arthritis, ankylosing spondylitis and psoriasis. If authorized by the EMA, SB2 could be available for use in all of the same indications as Remicade. Samsung Bioepis previously conducted SB2 Phase I and Phase III clinical studies. The MAA for the infliximab biosimilar candidate was based on data from a Phase III, controlled, randomized, multicenter study in Europe where SB2 demonstrated its comparability to Remicade. The primary and secondary endpoints of the Phase III study were assessed and met the qualification standard for the MAA submission. Full data from the study will be available later this year    

Patents:

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: 2017-04-21

UE authorization: 2016-05-30

Favourable opinion UE: 2016-04-01

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes