Likely to be degraded in infant's GI tract

Long half-life increases risk of accumulation in breastfed infants

Limited published evidence of safety indicates small amounts in breast milk

Avoid in preterm infants and neonates as large protein molecules may appear in colostrum

Sep 17: Launched in EU [6].

---

Sep 17: Approved in EU [5]

---

Jul 17: Proposed licence is treatment of paediatric chronic non-infectious anterior uveitis in patients from 2 years of age who have had an inadequate response to or are intolerant to conventional therapy, or in whom conventional therapy is inappropriate [3].

---

Jul 17: Positive opinion in EU for paediatric license extension for adalimumab (Humira) for uveitis, based on results from SYCAMORE trial [3].

·

About 1000 children are diagnosed with juvenile idiopathic arthritis (JIA) in the UK per year, and about 10,000 children have the condition. It is associated with a range of extra-articular manifestations, notably uveitis; about 30–50% of children with JIA have uveitis at diagnosis [1]. ·

July 17: Results of SYCAMORE (EudraCT number, 2010-021141-41) trial published in NEJM. Children and adolescents ≥2 years with active JIA associated uveitis on a stable dose of MTX were assigned 2:1 to receive either HUMIRA or placebo, every 2 weeks until treatment failure or until 18 months had elapsed. Primary endpoint was time to treatment failure, based on the Standardization of Uveitis Nomenclature (SUN) criteria. There were 16 treatment failures in 60 patients (27%) in the HUMIRA group vs 18 treatment failures in 30 patients (60%) in the placebo group HR 0.25[0.12 to 0.49], P<0.0001 [4].

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Jun 16: ADJUVITE (NCT01385826) trial completed

---

Jun 11: A PII/III study assessing the efficacy of adalimumab versus placebo on reduction of ocular inflammation quantified by laser flare photometry after two months of treatment in patients with active uveitis despite well conducted treatment with steroid eye drops and MTX begins (ADJUVITE; NCT01385826). The primary objective is to demonstrate a higher response rate at 2 months in the adalimumab arm versus the placebo arm. Patients will be considered as responding patients if their evaluated eye, 2 months after inclusion, presents at least 30% reduction of inflammation on laser flare photometry and improvement or a stable appearance on slit lamp examination. After the second month, all patients wishing to continue the trial and presenting a satisfactory clinical state will be treated with adalimumab for a total of one year after inclusion to descriptively evaluate the efficacy and safety of treatment over 10 to 12 months. 34 children aged 4 years or older will be recruited in France. Collection of primary outcome is expected to complete in Nov 15 [2].

·

AWMSG ·

Oct 18: Amgevita 20mg/0.4ml soln for inj in pre-filled syringe, Price =£158.40. Amgevita 40mg/0.8ml soln for inj in pre-filled syringe or pre-filled pen, Price =£633.60 [16].

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Oct 18: Amgevita launched in markets across Europe on 16th October 2018 [15]

---

Sep 17: Under a new settlement with AbbVie, Amgen has agreed to wait until end Jan 2023 before launching its adalimumab biosimilar (Amjevita) in the US. Launch in Europe is expected Oct 2018 [15]

---

Mar 17: Approved in EU for all indications of originator product [14]

---

Jan 17: EU positive opinion for treatment of rheumatoid arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis, hidradenitis suppurativa, Crohn’s disease, ulcerative colitis and uveitis [13]

---

Sep 16: Approved in the US for all eligible indications of its reference product, including moderate-to-severe rheumatoid arthritis, moderate-to-severe polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, moderate-to-severe chronic plaque psoriasis, adult moderate-to-severe Crohn´s disease and moderate-to-severe ulcerative colitis. The approval follows analytical, nonclinical, pharmacokinetic and clinical data showing biosimilarity between Amjevita and Humira, including results from two PIII studies conducted in moderate-to-severe plaque psoriasis and moderate-to-severe rheumatoid arthritis patients which met their primary endpoint showing clinical and safety equivalence [11]

---

Jul 16. The FDA recommends approval of ABP 501 in all available indications to the reference product

---

Jan 16: The FDA accepts the application for ABP 501, with a final decision expected by Sep 25. Amgen hope ABP 501 will be approved for all Humira indications. However, launch in the US may be delayed. The US Patent and Trademark Office has declined to review a pair of AbbVie patents that Amgen contends are invalid, a blow to Amgen plans to market its biosimilar by 2017. Amgen has promised to challenge those patents in court, but AbbVie believes its legal protection will keep Humira safe from competition until 2022 [9]

---

Dec 15: Filed in the EU using PIII data in which ABP-501 met primary and secondary endpoints of improving RA symptoms at a rate similar to Humira with a comparable safety profile [8]

---

Nov 15: Filed in the US [7]

---

Feb 15: patents covering adalimumab will expire in 2016 in the US and in 2018 in the EU [4]

---

Feb 13: Amgen announce it aims to begin launch of its adalimumab biosimilar in 2017 [4]

---

·

NICE suggest the benchmark rate for the number of people with RA eligible for and receiving biologic drugs is 86 per 100,000 adults per year ·

01. Oct 13: Amgen is to start a PIII multicentre, double-blind, randomized trial of its biosimilar version of adalimumab (ABP 501) vs the reference product Humira, in patients suffering from severe rheumatoid arthritis. The primary outcome is ACR20 at week 24. The trial, which is expected to take 11 months, will be conducted in Argentina, Bulgaria, Canada, Czech Republic, Germany, Hungary, Mexico, Poland, Romania, Russia, Spain, UK and the US and will include 500 patients, aged 18 years and above. EudraCT Number: 2013-000525-31 [1]. ·

02. The PIII study is also registered on clinicaltrials.gov as study NCT01970475. The study will enrol 500 subjects and is due to complete Aug 15. ·

03. Apr 14: NCT02114931 is an an open-label, single-arm PIII extension study to evaluate the long-term safety and efficacy of ABP 501 in 425 subjects with moderate to severe rheumatoid arthritis. The study starts Apr 14 and is due to complete Feb 17 [2] ·

04. Feb 15: Positive top-line results from PIII study evaluating efficacy and safety of Abp 501 vs. Humira® (adalimumab) in 526 adult pts with moderate-to-severe RA who have an inadequate response to methotrexate (MTX).. This randomised, double-blind, active-controlled study (20120262) evaluated safety, efficacy and immunogenicity of ABP 501 (n=264) compared to adalimumab (n=262) given subcutaneously every 2 weeks. The study consisted of; a screening period of 4 weeks, a treatment period of 22 weeks and a safety follow-up period through to week 26. The primary endpoint, assessment of ACR20 at week 24, was met as well as key secondary endpoints (ACR50, ACR70 and DAS 28-CRP). The ACR20 was within the prespecified margin for ABP 501 compared to adalimumab, showing clinical equivalence. Safety and immunogenicity of ABP 501 were comparable to adalimumab [3]. ·

05. Sep 15: Study with EudraCT Number: 2013-000525-31 involving 500 patients with rheumatoid arthritis completed Nov 14, no results currently available.[5] ·

06. Nov 15: Amgen presented detailed findings from a head-to-head Phase 3 study comparing the safety, efficacy and immunogenicity of ABP 501 with adalimumab in patients with moderate-to-severe RA, at the 2015 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) Annual Meeting in San Francisco. The study met the primary endpoint, which was achievement of ACR20 (20% or greater improvement in ACR assessment) at week 24. At week 24, 74.6% of patients in the ABP 501 group and 72.4% in the adalimumab group met the ACR20 response criteria. The risk ratio of ACR20 was 1.039 with the two-sided 90 percent CI of 0.954–1.133, which fell within the predefined equivalence margin [6]. ·

07. Nov 15: Further details from the PIII (20120262) study announced. Secondary endpoints included the achievement of ACR50 and ACR70 (a 50 or 70 percent improvement in ACR assessment) within the predefined equivalence margin. At week 24, patients treated with ABP 501 compared with those treated with adalimumab achieved ACR50 (49.2% vs. 52.0%) and ACR70 (26.0% vs. 22.9%, respectively. Additionally, the secondary endpoint of a difference in change from baseline of DAS28-CRP (Disease Activity Score examines 28 joints in the body as measured by C reactive protein in the blood) over the entire study was also achieved. The difference in mean change from baseline in DAS28-CRP between ABP 501 and adalimumab was –0.01 (90% CI, –0.18 to 0.17) at week 24. The incidence of treatment-emergent adverse events (TEAEs) was 50 percent for ABP 501 and 55 percent for adalimumab. The most frequently reported TEAEs (for ABP 501 and adalimumab, respectively) were nasopharyngitis (6.4% vs. 7.3%), headache (4.5% vs. 4.2%), arthralgia (3.0% vs. 3.4%), cough (2.7% vs. 3.1%) and upper respiratory tract infection (1.5% vs. 3.8%). Serious adverse events (3.8% vs. 5.0%) and serious infections (0.8% vs. 1.1%) were reported in patients treated with ABP 501 and adalimumab, respectively. By the end of week 24, binding antibodies (38.3% vs. 38.2%) and neutralizing antibodies were identified (9.1% vs. 11.1%) in patients treated with ABP 501 and adalimumab, respectively [6]. ·

08. Oct 16: results of trial NCT01970475 that compared ABP 501 with adalimumab (Humira) in patients with moderate-severe RA found those who achieved ACR 20 was similar with the two treatments, 74.6% vs 72.4% respectively [12]. ·

Amgevita EPAR ·

SMC ·

Solymbic EPAR ·

01. Feb 15: patents covering adalimumab will expire in 2016 in the US and in 2018 in the EU [4]. ·

02. Feb 13: Amgen announce it aims to begin launch of its adalimumab biosimilar in 2017 [4] ·

03. Nov 15. Filed in the US [6]. ·

04. Dec 15: Filed in the EU. Amgen´s MAA submission includes analytical, clinical and pharmacokinetic data. PIII comparative efficacy and safety studies were conducted in both moderate-to-severe plaque psoriasis and moderate-to-severe RA, which met their primary endpoints showing clinical equivalence to adalimumab. Safety and immunogenicity of ABP-501 were also comparable to adalimumab in both studies. Data to support the transition of adalimumab patients to ABP-501 are included in the submission. [7]. ·

05. Jan 16: The FDA accepts the application for ABP 501, with a final decision expected by Sep 25. Amgen hope ABP 501 will be approved for all Humira indications. However, launch in the US may be delayed. The US Patent and Trademark Office has declined to review a pair of AbbVie patents that Amgen contends are invalid, a blow to Amgen plans to market its biosimilar by 2017. Amgen has promised to challenge those patents in court, but AbbVie believes its legal protection will keep Humira safe from competition until 2022 [9]. ·

06. .Jul 16. The FDA recommends approval of ABP 501 in all available indications to the reference product [9] ·

07. Sep 16: Approved in the US for all eligible indications of its reference product, including moderate-to-severe rheumatoid arthritis, moderate-to-severe polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, moderate-to-severe chronic plaque psoriasis, adult moderate-to-severe Crohn´s disease and moderate-to-severe ulcerative colitis. The approval follows analytical, nonclinical, pharmacokinetic and clinical data showing biosimilarity between Amjevita and Humira, including results from two PIII studies conducted in moderate-to-severe plaque psoriasis and moderate-to-severe rheumatoid arthritis patients which met their primary endpoint showing clinical and safety equivalence [11]. ·

08. Jan 17: EU positive opinion for treatment of rheumatoid arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis, hidradenitis suppurativa, Crohn’s disease, ulcerative colitis and uveitis [12]. ·

09. Mar 17: Approved in EU for all indications of originator product [13]. ·

10. Sep 17: Under a new settlement with AbbVie, Amgen has agreed to wait until end Jan 2023 before launching its adalimumab biosimilar (Amjevita) in the US. Launch in Europe is expected Oct 2018 [14]. ·

11. Oct 18: Amgevita launched in markets across Europe on 16th October 2018 [16]. ·

12. Oct 18: Amgevita 20mg/0.4ml soln for inj in pre-filled syringe, Price =£158.40. Amgevita 40mg/0.8ml soln for inj in pre-filled syringe or pre-filled pen, Price =£633.60. [16] ·

Plaque psoriasis is the most common type of psoriasis, representing 90% of cases. Around 2-3% of the overall UK population have psoriasis and it is estimated that 1.4% of all people between the ages of 10 and 19 are affected. Approximately 1.1% of people with plaque psoriasis have severe disease. ·

01. Oct 13: EudraCT Number: 2013-000537-12 is a PIII, multicentre, randomized, double-blind study evaluating the efficacy and safety of ABP 501 vs adalimumab in 340 subjects with moderate to severe plaque psoriasis. The primary efficacy endpoint is PASI % improvement from baseline at week 16. The trial will be conducted in Poland, Australia, Canada, France, Germany and Hungary and started Sep 13 [1]. ·

02. The PIII study is also registered on the clinicaltials.gov website as study NCT01970488. The study is due to complete Mar 16 (primary data collection Aug 15). ·

03. Oct 14: Amgen announces ABP 501 met trial outcomes of equivalent efficacy and safety for treating plaque psoriasis in the first of two planned PIII studies comparing its follow-on drug with Humira. Humira loses patent protection in the US in 2016 and in Europe in 2018 [3]. ·

04. Sep 15: The phase III, multicenter, randomized, double-blind study evaluating the efficacy and safety of ABP 501 compared with adalimumab (Humira) in 350 subjects with moderate to severe plaque psoriasis (NCT01970488) completed in March 2015 (Primary completion date was July 2014)Primary Outcome Measure was: Psoriasis Area and Severity Index (PASI) % improvement after 16 weeks; secondary endpoint was PASI response at week 50. No results currently available[5]. ·

05. Oct 16: PIII study to compare efficacy of ABP501 with adalimumab in moderate-severe psoriasis (NCT01970488) found comparable efficacy; 80.91% vs 83.06% met primary outcome of improvement in PASI from baseline to week 16 [11]. ·

Amgevita EPAR ·

Solymbic EPAR ·

Nov 18: Hyrimoz approved by FDA for rheumatoid arthritis, juvenile idiopathic arthritis in patients four years of age and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn's disease, ulcerative colitis and plaque psoriasis. Despite the approval, Hymiroz will not be available in the US until 2023, under terms of intellectual property-related litigation with AbbVie.[13]

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Oct 18: Following patent disputes, Sandoz announce agreement with AbbVie to delay launch of its adalimumab biosimilar in the US until Sept 2023 [12].

---

Oct 18: Launched in the UK. Cost for 2 x 40mg/0.8ml soln for inj in pre-filled syringe or pre-filled pen=£646.18 [11].

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Jul 18: Approved in the EU [10].

---

May 18: recommended for EU approval by CHMP - indications encompass those of Humira, but differ in detail between the three brand names [9].

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Dec 17: Currently pre-registration in US [8].

---

Jun 17: Filed in EU [1]

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Sep 16: EU filing planned 2017 [3].

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Sep 16: Filings planned in the US 2016 [3].

---

Feb 15: patents covering adalimumab will expire in 2016 in the US and in 2018 in the EU [2]

·

Plaque psoriasis is the most common type of psoriasis, representing 90% of cases. Around 2-3% of the overall UK population have psoriasis and it is estimated that 1.4% of all people between the ages of 10 and 19 are affected. Approximately 1.1% of people with plaque psoriasis have severe disease. ·

Sep 17: Sandoz present data from PIII NCT02016105 (ADACCESS) at conference. PASI 75 response rates for patients receiving biosimilar adalimumab continuously throughout the study were 75.2% at Week 17 and 84.5% at Week 51, compared with 67.8% and 79.6%, respectively, for patients receiving continuous Humira [7].

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Mar 17: PIII trial to compare efficacy and safety of GP2017 and Humira in plaque psoriasis confirmed equivalent efficacy by demonstrating PASI 75 response rates of 67% for GP2017and 65% for Humira after 16 weeks treatment in patients with moderate to severe, chronic plaque psoriasis [5].

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Sep 16: PIII trial to compare efficacy and safety of GP2017 and Humira in plaque psoriasis completed (NCT02016105), no results available [4].

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Sep 15: Patient enrolment complete [2].

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Dec 13: NCT02016105 a randomized, double-blind, multicentre study to demonstrate equivalent efficacy and to compare safety and immunogenicity of a biosimilar adalimumab (GP2017) and Humira® in 448 patients with moderate to severe chronic plaque-type psoriasis. The primary outcome is PASI 75 response rate at week 17. The study starts Dec 13 and is due to complete Dec 15 (primary outcome data collection Jun 15). The trial will support registration in the US and EU [1].

·

Nov 18: Hyrimoz approved by FDA for rheumatoid arthritis, juvenile idiopathic arthritis in patients four years of age and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn's disease, ulcerative colitis and plaque psoriasis. Despite the approval, Hymiroz will not be available in the US until 2023, under terms of intellectual property-related litigation with AbbVie.[13]

---

Oct 18: Following patent disputes, Sandoz announced agreement with AbbVie concerning the proposed biosimilar for reference medicine Humira which means launch in the US will be delayed until Sept 2023 [8]

---

Oct 18: Launched in the UK. Cost for 2 x 40mg/0.8ml soln for inj in pre-filled syringe or pre-filled pen=£646.18 [7].

---

Jul 18: Approved in the EU [6].

---

May 18: recommended for EU approval by CHMP - indications encompass those of Humira, but differ in detail between the three brand names [5].

---

Jan 18: FDA accept Biologics License Application (BLA) for filing for adalimumab biosimilar.[5

---

Dec 17: Currently pre-registration in US [4].

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Jun 17: Filed in EU [1].

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Sep 16: EU filing planned for 2017 [2].

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Sep 16: US filing planned for 2016 [2].

·

NICE suggest the benchmark rate for the number of people with RA eligible for and receiving biologic drugs is 86 per 100,000 adults per year ·

Mar 16: NCT02744755 is a PIII randomized, double-blind study to demonstrate similar efficacy and to compare safety and immunogenicity of GP2017 and Humira® in 308 patients with moderate to severe active rheumatoid arthritis. The study started in Mar 16 and is due to complete Oct 17. Primary outcome data on change in DAS28-CRP score at week 12 will be collected by Feb 17 [1].

·

Oct 18: Adalimumab 40mg/0.8ml soln for inj in pre-filled syringe or pre-filled pen, Price = £633.85 [12]

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Oct 18: Launched in EU [11]

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Apr 18: AbbVie announces global resolution of Humira (adalimumab) patent disputes with Samsung Bioepis. Under the terms of the agreement, Imraldi may be launched in Europe from Oct 18. Merck & Co, Samsung´s commercialisation partner for the US, can launch in Jun 23 [9,10]

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Aug 17: Approved in EU [7]

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Jun 17: EU positive opinion for treatment of rheumatoid arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis, paediatric plaque psoriasis, hidradenitis suppurativa, Crohns disease, paediatric Crohns disease, ulcerative colitis and uveitis [6]

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Jul 16: SB5 has been accepted for review by the EMA [4]

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Nov 15: The 24-week PIII study of SB5, which randomised 544 pts with moderate to severe RA despite methotrexate therapy, showed ACR20 response rate of 72.5% in the SB5 arm vs. 72.0% in the Humira® arm. The safety profile of SB5 was comparable to Humira® [3]

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Jul 15: Samsung Bioepis and Merck intend to file applications for the approval of adalimumab by 2016 [2]

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Feb 13: Merck & Co. and Samsung Bioepis enter into an agreement. Samsung Bioepis has responsibility for preclinical and clinical development, process development and manufacturing, clinical trials and registration; Merck & Co. has responsibility for commercialisation worldwide excluding the territories of the EU, Russia and Turkey [1]

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·

NICE suggest the benchmark rate for the number of people with RA eligible for and receiving biologic drugs is 86 per 100,000 adults per year. ·

01. Apr 14: Samsung Bioepis initiates a PIII trial to evaluate safety, efficacy, tolerability, pharmacokinetics and immunogenicity of its adalimumab biosimilar, compared with Humira in adult and elderly patients with moderate to severe RA (SB5-G31-RA; EudraCT2013-005013-13). The primary objective of the study is to demonstrate the equivalence of the two agents in terms of response rate at week 24. The trial will enrol approximately 490 patients. Enrolment has begun in Lithuania, Bulgaria and Poland, and will extend to other countries [2]. ·

02. Jul 15: Samsung Bioepis announces SB5 met its main goal of measuring up to adalimumab in a PIII study on patients with RA, charting at least a 20% average improvement in symptoms after 24 weeks [1]. ·

03. Jul 16: PIII study lasting 62 weeks randomised 544 patients with moderate to severe rheumatoid arthritis despite methotrexate therapy to either SB5 or adalimumab (Humira). Results at 24-weeks showed ACR20 response rate of 72.5% in the SB5 arm versus 72.0% in the adalimumab arm. The safety profile of SB5 was comparable to adalimumab and the incidence of anti-drug antibody was 15.7% in the SB5 group and 18.3% in the Humira group [4]. ·

04. Aug 16: PIII trial where 508 patients with rheumatoid arthritis were randomized in a 1:1 ratio to receive either SB5 or Humira (adalimumab) 40 mg every other week. At Week 24, 254 patients from SB5 continued to receive SB5 (SB5/SB5), 125 patients from Humira were transitioned to SB5 (adalimumab/SB5) and 129 patients from Humira continued to receive Humira (adalimumab/adalimumab). At Week 52, the efficacy, safety and immunogenicity profiles were comparable, with ACR20 response rates of 76.9%, 81.1% and 71.2%, respectively. There were no treatment emergent issues or clinically relevant immunogenicity precipitated by switching. At week 52, the incidence of anti-drug antibodies was 15.7% in SB5/SB5, 16.8% in adalimumab/SB5 and 18.3% in adalimumab/adalimumab [5]. ·

05. Nov 17: Results of 24-week PIII study of SB5 (NCT02167139) published in Arthritis and Rheumatology [8]. ·

EPAR ·

NICE ·

Oct 18: Mylan N.V. announced that it has initiated the commercial launch of Hulio across major markets in Europe [9].

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Sep 18: Launch anticipated mid Oct 2018 [8]

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Sep 18 Approved in the EU [7]

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Jul 18: EU positive opinion for treatment of rheumatoid arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis, paediatric plaque psoriasis, hidradenitis suppurativa, Crohn´s disease in adults and children, ulcerative colitis and uveitis in adults and children [6].

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May 17: the European Medicines Agency (EMA) accepted the Marketing Authorisation Application (MAA) for FKB327, an adalimumab biosimilar, for review on May 18, 2017 [4].

·

NICE suggest the benchmark rate for the number of people with RA eligible for and receiving biologic drugs is 86 per 100,000 adults per year ·

Mar 17: Pharmacokinetic similarity of FKB327 with Humira demonstrated in healthy subjects (n=180). FKB327 was well tolerated with AE´s similar to Humira (EudraCT 2012–005140-23) [3].

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Jul 16: PIII efficacy/safety trial completed in rheumatoid arthritis (NCT0220791), no study results posted [3]

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Jul 15: PIII ARABESC-OLE open extension trial in 480 patients started, to evaluate the safety/efficacy/immunogenicity of adalimumab biosimilar in patients who completed the ARABESC trial [2].

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Jan 15: PIII ARABESC efficacy/safety trial comparing FKB-327 with Humira in 600 patients with rheumatoid arthritis inadequately controlled on methotrexate (EudraCT2014-000109-11; NCT02260791) in US/Canada, Germany, Spain, and other countries [1].

·

EPAR ·

Dec 18: Boehringer Ingelheim has said that it will not commercialize its approved adalimumab biosimilar Cyltezo (BI 695501) in Europe and is discontinuing all biosimilar development activities outside the US [12].

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Nov 17 Approved in EU [6]

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Sep 17: EU positive opinion for treatment of rheumatoid arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis, paediatric plaque psoriasis, hidradenitis suppurativa, Crohn’s disease, paediatric Crohn´s disease, ulcerative colitis and uveitis [5].

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Aug 17: Approved in US [4]

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Jan 17: company announces that both the EMA and the FDA have accepted regulatory filings for BI695501 adalimumab biosimilar - the media release states that the product is intended for treatment of ´inflammatory diseases´ but doesn´t indicate whether it has been filed for one indication or for all those currently licensed for Humira [2].

·

July 17: Boehringer Ingelheim initiates a PIII study (NCT03210259) to evaluate efficacy, safety and immunogenicity of BI-695501 compared to Humira® in patients with plaque psoriasis. The trial will compare the pharmacokinetics and clinical outcomes between patients receiving Humira® continuously, vs those who switch repeatedly between Humira® and BI 695501 [3].

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Oct 16: PIII study to evaluate efficacy safety and immunogenicity of BI 695501 Versus Humira® in Patients With Moderate to Severe Chronic Plaque Psoriasis now started (NCT02850965), with primary outcome PASI 75 response at week 16 [1].

·

EPAR ·

Dec 18: Boehringer Ingelheim has said that it will not commercialize its approved adalimumab biosimilar Cyltezo (BI 695501) in Europe and is discontinuing all biosimilar development activities outside the US [7].

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Nov 17: Approved in EU [12]

---

Sep 17: EU positive opinion for treatment of rheumatoid arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis, paediatric plaque psoriasis, hidradenitis suppurativa, Crohn’s disease, paediatric Crohn´s disease, ulcerative colitis and uveitis [11].

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Aug 17. Approved in US [10]

---

Jan 17: company announces that both the EMA and the FDA have accepted regulatory filings for BI695501 adalimumab biosimilar - the media release states that the product is intended for treatment of ´inflammatory diseases´ but doesn´t indicate whether it has been filed for one indication or for all those currently licensed for Humira [8].

---

Apr 15: PIII [2].

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PI study conducted in New Zealand [1].

·

Prevalence ranges from 0.5-1.5% of the population in industrialised countries. The incidence of the condition is low, with around 1.5 men and 3.6 women developing RA per 10,000 people per year. ·

Mar 18: Results of VOLTAIRE-RA equivalence study (NCT02137226) published. RCT (n=645) found BI 695501 demonstrated similar efficacy, safety and immunogenicity to Humira. At week 12, 61.1% and 67.0%, respectively, achieved ACR20; at week 24 corresponding values were 64.5% and 69.0%. Switching from Humira to BI 695501 had no impact on efficacy and safety [11].

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Jul 17: Boehringer Ingelheim announced that the first patient has been enrolled into its VOLTAIRE-X interchangeability study. The goal of the study is to demonstrate that BI 695501 is interchangeable with the U.S.-marketed formulation of Humira® 40 mg/0.8 mL. This is the first study in the U.S. to investigate an interchangeability designation for an adalimumab biosimilar candidate. The study will compare the pharmacokinetics and clinical outcomes between patients receiving Humira continuously, versus those who switch repeatedly between Humira and BI 695501, Boehringer Ingelheim’s adalimumab biosimilar candidate. The study will also assess safety, immunogenicity and efficacy [9].

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Oct 16: Boehringer Ingelheim announces BI 695501 shows similar efficacy and safety profile to Humira® in pivotal PIII study NCT02137226. In this 48 week RCT (n=645) both primary efficacy endpoint (to establish equivalence with Humira®) and secondary endpoints (efficacy, safety and immunogenicity of BI 695501 vs. Humira®) were met [7].

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Nov 15: Recruitment to PIII trial of BI 695501 vs adalimumab lasting 48 weeks in patients with rheumatoid arthritis is now complete [6].

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Sep 15: A PIII trial investigating efficacy, safety and immunogenicity of BI 695501 versus adalimumab in patients with active rheumatoid arthritis (EUDRA-CT no 2012-002945-40) started in Sept 2014 involving 600 patients in Germany Hungary Spain Estonia and Bulgaria and is ongoing. Outcomes include Disease Activity Score in 28 joints (DAS28) [5].

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Jun 15: PIII NCT02137226 study is currently recruiting. It is expected to complete collection of primary outcome data in Apr 2016 [4].

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Jan 15: Boehringer Ingelheim initiates a PIII study to evaluate efficacy, safety and immunogenicity of BI-695501 compared to commercially available adalimumab sourced from the US, in adult and elderly patients with RA (NCT02137226). The primary endpoints will be change from baseline in DAS 28 and proportion of patients achieving ACR 20, both at 24 weeks. The global trial will enrol 650 patients. Enrolment has begun in Germany, Hungary, Estonia, Bulgaria, Poland and Spain [3].

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NCT01505491 is a randomized, open-label, single dose, parallel arm, active comparator PI study of the pharmacokinetics and safety of BI 695501 in 193 healthy subjects. The study was conducted in New Zealand. It started in Dec 11 and completed Jul 12 [1].

·

EPAR ·

Psoriasis is a common, chronic relapsing autoimmune-mediated inflammatory skin disorder. The prevalence of psoriasis is estimated to be about 1.3-2.2% in the UK. Plaque psoriasis accounts for 90% of all people with psoriasis, the majority of cases first present before the age of 35 [2]. ·

NICE suggest the benchmark rate for the number of people with RA eligible for and receiving biologic drugs is 86 per 100,000 adults per year ·

NICE suggest the benchmark rate for the number of people with RA eligible for and receiving biologic drugs is 86 per 100,000 adults per year ·

In the UK the population minimum prevalence of RA was 1.16% in women and 0.44% in men in one study [2]. ·