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Articles
Safety in lactation: Drugs for chronic bowel disorders
21 September 2020Additional information relating to breastfeeding To be used in conjunction with individual drug entries for specific information and guidance. Aminosalicylates for chronic bowel disorders Mesalazine…
Safety in Lactation: Systemic preparations for eczema and psoriasis
7 January 2019Drugs used orally or parenterally for severe eczema and psoriasis have a varied pharmacology, mainly either modifying the immune response to the disease or modifying…
Refrigerated Storage
HumiraAbbVie
AbbVie
Humira
40 mg solution for injection pre-filled syringe, pre-filled pen
In the event of an inadvertent temperature excursion the following data may be used:
A single Humira pre-filled syringe or pre-filled pen may be stored at temperatures up to a maximum of 25°C for a period of up to 14 days. The syringe or pen must be protected from light, and discarded if not used within the 14 -day period
Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk
For information outside of this excursion, contact AbbVie Ltd directly. Refer to the current BNF for company contact details.
25 March 2021
London MI Service
Amgevita Amgen Ltd
Amgen Ltd
Amgevita
Solution for injection in pre-filled syringe/pen
In the event of an inadvertent temperature excursion the following data may be used:
The pre-filled syringe or pre-filled pen may be stored at temperatures up to a maximum of 25°C for a period of up to 14 days. The pre-filled syringe or pre-filled pen must be protected from light, and discarded if not used within the 14-day period.
Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk
15 March 2021
London MI Service
ImraldiBiogen
Biogen
Imraldi
Solution for injection in a pre-filled pen or syringe
Once exposed to temperatures up to 25°C, the syringe or pen must be used within 28 days or discarded, even if it is returned to the refrigerator.
You should record the date when the syringe or pen is first removed from refrigerator, and the date after which it should be discarded.
Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk
19 March 2021
London MI Service
HyrimozSandoz
Sandoz
Hyrimoz
20mg and 40mg Solution for injection in pre-filled syringe and pen
In the event of an inadvertent temperature excursion the following data may be used:
A single Hyrimoz pre-filled syringe / pre-filled pen may be stored at temperatures up to a maximum of 25°C for a period of up to 21 days. The pre-filled syringe / pre-filled pen must be protected from light, and discarded if not used within the 21-day period.
The manufacturers have stated that they will deal with temperature excursions on a case by case basis to ensure the most up to date information is provided each time. Refer to the current BNF for company contact details.
Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk
28 September 2020
London MI Service
Lactation Safety Information
For rheumatoid arthritis
For rheumatoid arthritis
See summary
Moderate amount of published evidence of safety indicates small amounts in breast milk which are likely to be degraded in the infant’s GI tract
Long half-life increases risk of accumulation in breastfed infants
Although large protein molecules may appear in colostrum, risk to preterm infants and neonates is considered to be small and unproven
15 September 2019
New Medicines
HumiraModerate-to-severe ulcerative colitis (UC) in children unable to have conventional therapies
Information
Humira
Licence extension / variation
AbbVie
AbbVie
Development and Regulatory status
Launched
Launched
Phase III Clinical Trials
November 2020
Nov 20Licence extension approved in the EU [6].
Oct 20Recommended for EU approval by CHMP - the additional indication is "for the treatment of moderately to severely active ulcerative colitis in paediatric patients (from 6 years of age) who have had an inadequate response to conventional therapy including corticosteroids and/or 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies" [5].
Category
TNF-alfa antagonist
Ulcerative colitis is the most common type of inflammatory disease of the bowel. It has an incidence in the UK of approximately 10 per 100,000 people annually and a prevalence of approximately 240 per 100,000. Ulcerative colitis can develop at any age but peak incidence is between the ages of 15 and 25 years, with a second, smaller peak between 55 and 65 years [1].
Moderate-to-severe ulcerative colitis (UC) in children unable to have conventional therapies
Subcutaneous injection
Trial or other data
Jun 21Analysis of PIII ENVISION I trial (n=77;age 4-17 years), showed a significantly higher proportion of patients were in partial Mayo score (PMS) remission at 8 weeks with high-dose induction adalimumab vs placebo (60 vs 19.8%;p=0.0001) and similarly with full MS remission at week 52 in 8 week PMS responders (45 vs 18.4%;p=0.0001) [7].
Jan 20The PIII study NCT02065557, and the open-label long-term PIII trial are ongoing, with estimated primary completion dates of Jun 2020 and May 2023, respectively [4].
Nov 18The PIII study NCT02065557 is still recruiting with estimated primary completion date of May 2021. The open-label long-term PIII trial is still enrolling by invitation with estimated primary completion date of May 2023 [3].
Jan 18PIII study (NCT02065557) is still recruiting [2].
Nov 15Open-label long-term safety and efficacy PIII trial of repeated SC injections of adalimumab in paediatric subjects with ulcerative colitis, who completed M11-290 study starts (M10-870; NCT02632175). The single-group trial is recruiting 93 patients, by invitation only, in the US, Slovakia and Japan [2].
Aug 14PIII trial to investigate the efficacy, tolerability, and pharmacokinetics of induction and maintenance therapy with adalimumab in paediatric patients with moderate to severe ulcerative colitis starts (M11-290; NCT02065557). The trial is intended to enrol 225 patients aged 4 to 17 years old from sites around the world including the US and EU (incl. UK). Collection of primary outcome data (clinical remission at 8 and 52 weeks) is due to complete May 21 [2].
Evidence based evaluations
Idacio, KromeyaRheumatoid arthritis (RA) and other Humira indications
Information
Idacio, Kromeya
Biosimilar
Fresenius Kabi
Fresenius Kabi
Development and Regulatory status
Launched
Launched
Phase III Clinical Trials
April 2020
Jan 22New paediatric indication approved for Idacio 40 mg/0.8 mL solution for injection. Full indication is "treatment of moderately to severely active ulcerative colitis in paediatric patients (from 6 years of age) who have had an inadequate response to conventional therapy including corticosteroids and/or 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies "[12].
Apr 20Available in the UK. 2 pack of pre-filled syringes = £633.86, 2 pack of pre-filled pens = £633.86 and 1 pack of solution for injection vials = £316.93 [10,11].
May 19Launched in Germany, where it is available as a pre-filled syringe, pre-filled pen and in a vial presentation [9].
Apr 19Fresenius announced on 3 April 2019 that it had received European Commission (EC) approval for its adalimumab biosimilar MSB11455 (Idacio) [8].
Apr 19Fresenius announced on 3 April 2019 that it had received European Commission (EC) approval for its adalimumab biosimilar MSB11455 (Idacio) [8].
Jan 19Proposed licensed indications include treatment of rheumatoid, juvenile idiopathic and psoriatic arthritis, axial spondyloarthritis, psoriasis, hidradenitis suppurativa, Crohn’s disease, ulcerative colitis and uveitis [7].
Jan 19Recommended for EU approval by CHMP - indicated for rheumatoid arthritis and other indications of Humira [7].
Dec 18Fresenius Kabi plans to launch adalimumab biosimilar in Europe in H1 2019 [6].
Dec 17Preregistration for psoriasis, PIII for RA [5].
Apr 17Merck KgA announces it is divesting its biosimilar business to Fresenius, closing expected H2 2017 [4].
Feb 16PIII trial (AURIEL-PsO; NCT02660580) trial of MSB11022 for the treatment of moderate to severe chronic plaque psoriasis initiated in Germany [2].
Category
A biosimilar version of adalimumab, a humanised recombinant monoclonal IgG1 antibody targeting tumour necrosis factor (TNF)-α.
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
Rheumatoid arthritis (RA) and other Humira indications
Subcutaneous injection
Trial or other data
Mar 16Merck KGaA announce first patient treated in adalimumab biosimilar candidate study[3].
Feb 16AURIEL-PsO (NCT02660580) will compare the safety, efficacy and immunogenicity of MSB 11022 to Humira® and will enrol approximately 406 patients in Germany; enrolment is expected to expand in the US, Bulgaria, Canada, Czech, Estonia, France, Germany, Hungary, Mexico, Poland, Romania, Russia and the UK [2].
YuflymaRheumatoid arthritis (RA) and other Humira indications - 40mg strength pre-filled pen and syringe
Information
Yuflyma
Biosimilar
Celltrion
Celltrion
Development and Regulatory status
Launched
Approved (Licensed)
Phase III Clinical Trials
August 2021
Aug 21Yuflyma 40mg/0.4ml pre-filled syringe or pre-filled pen available in the UK [12].
Jul 21NHS indicative price announced for Yuflyma 40mg/0.4ml solution for injection pre-filled pens, £633.70 for 2 pens. Launch is presumably imminent [11].
Feb 21Approved in UK by MHRA [10].
Feb 21Celltrion will take the EC Decision Reliance Procedure (ECDRP) to minimise lead time to launch the product (Yuflyma) in the UK [9].
Feb 21Approved in EU [8].
Dec 20Yuflyma is a high concentration (100mg/ml) citrate free formulation [5]. It is a similar concentration that of Humira (20mg in 0.2ml, 40mg in 0.4ml etc [6], higher than other biosimilars.
Dec 20The proposed indications in the EU are rheumatoid arthritis in adults, juvenile idiopathic arthritis, axial spondyloarthritis in adults, psoriatic arthritis in adults, psoriasis in adults and children, hidradenitis suppurativa in adults and adolescents aged ≥12 years, Crohn’s disease in adults and children, ulcerative colitis in adults, and uveitis in adults and children [7].
Dec 20Recommended for EU approval by CHMP - approval covers all indications of the originator product [7].
Apr 20Currently pre-registration in the EU. Has been filed using the centralised procedure. The following indications are awaiting approval: RA, juvenile idiopathic arthritis, enthesis-related arthritis, ankylosing spondylitis, axial spondyloarthritis, PsA, psoriasis (adults and children), hidradenitis suppurativa, Crohns disease (adults and children), ulcerative colitis, and uveitis (adults and children) [4].
Apr 19Celltrion announced (Mar 19) that it had completed registering patients for its global phase III clinical trial of its candidate adalimumab biosimilar, CT P17 [3].
Aug 18Celltrion aims to complete phase 3 clinical trials by 2020 [1].
Aug 18CT-P17 is being developed as a high-concentration formulation differentiating it from the other biosimilars in trials or already approved [1].
Category
Tumour necrosis factor (TNF) inhibitor, citrate-free double concentrate (reduced volume) formulation. 40 mg solution for injection in pre-filled syringe.
In the UK the population minimum prevalence of RA was 1.16% in women and 0.44% in men in one study [2].
Rheumatoid arthritis (RA) and other Humira indications - 40mg strength pre-filled pen and syringe
Subcutaneous injection
Trial or other data
Jun 21Jun 21: Celltrion announce PIII trial (EudraCT2018-001690-25) of CT-517 vs Humira met its primary and secondary endpoints, demonstrating that the efficacy, pharmacokinetics, safety and immunogenicity of CT-517 is comparable to reference adalimumab in the treatment of patients with moderate-to-severe active RA up to one year [3].
Apr 20Trials used in support of a licence include single-arm PIII (NCT03789292) study in 50 patients with moderate to severe RA recruited in Eastern Europe, double-blind PIII (NCT03789292) study versus Humira, in combination with methotrexate, in 564 adults with moderate to severe RA recruited in Eastern Europe, and PI studies (NCT04295356 and NCT03970824) in healthy subjects recruited in North America and Asia, respectively [4].
Imraldi Ulcerative colitis (UC) in children aged 6 years and older
Information
Imraldi
Licence extension / variation
Biogen
Merck & Co (name used in US for MSD)
Development and Regulatory status
Launched
Launched
None
November 2021
Nov 21Approved by MHRA for treatment of moderately to severely active ulcerative colitis in paediatric patients (from 6 years of age) who have had an inadequate response to conventional therapy including corticosteroids and/or 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies [3].
Jul 21Approved in EU [2].
Jun 21EU positive opinion for a new indication of treatment of moderately to severely active ulcerative colitis in paediatric patients (from 6 years of age) who have had an inadequate response to conventional therapy including corticosteroids and/or 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies [2].
Category
A biosimilar version of adalimumab (SB 5), a humanised recombinant monoclonal IgG1 antibody targeting tumour necrosis factor (TNF)-α.
Ulcerative colitis is the most common type of inflammatory disease of the bowel. It has an incidence in the UK of approximately 10 per 100,000 people annually and a prevalence of approximately 240 per 100,000. Ulcerative colitis can develop at any age but peak incidence is between the ages of 15 and 25 years, with a second, smaller peak between 55 and 65 years [1].
Ulcerative colitis (UC) in children aged 6 years and older
Subcutaneous injection
Hukyndra, Libmyris Rheumatoid arthritis (RA), ankylosing spondylitis, plaque psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s Disease.
Information
Hukyndra, Libmyris
Biosimilar
Thornton & Ross (parent company Stada)
Teva
Development and Regulatory status
Approved (Licensed)
Recommended for approval (Positive opinion)
Pre-registration (Filed)
Apr 22Alvotech announces the resolution of all intellectual property disputes with AbbVie in Europe and selected markets outside of Europe, related to its AVT02 biosimilar candidate. This paves the way for STADA to commercialize AVT02 in European countries under the HUKYNDRA® brand name [13}
Feb 22Approved in UK by MHRA for same indications and presentations as EU [12].
Dec 21Approved in the EU [11].
Sep 21Recommended for EU approval by CHMP – approval covers all indications of the originator product. Stada have also received a positive opinion with the brand name Libmyris. Hukyndra and Libmyris will be available as 40mg solution for injection in a pre-filled syringe and pre-filled pen and 80mg solution for injection in a pre-filled syringe [10].
Mar 21Alvotech also has an agreement with Stada allowing it to commercialise seven biosimilars in Europe [8].
Mar 21Alvotech has an agreement with Teva Pharmaceuticals granting the latter rights to exclusively commercialise five biosimilars (including adalimumab) in the US [8].
Nov 20Concentration of AVT-02 is similar to Humira (100mg/ml), all other biosimilars currently marketed (Amgevita, Hyrimoz, Idacio, Imraldi) are 50mg/ml [7].
Nov 20Filed in the EU and US with an expected MAA in the EU of Q4 2021 [6].
Jun 20AVT 02 is being developed by Alvotech,as a biosimilar of adalimumab with higher concentration dosage forms for the treatment of autoimmune disorders, rheumatoid Arthritis and plaque psoriasis [5].
May 20Plans to file in EU in second half 2020 [2].
Aug 19AVT02 is in Phase-3 clinical development ahead of filing with the European Medicines Agency (EMA) and United States Food and Drug Administration (USFDA) by early 2020 [1].
Category
TNF inhibitor
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
Rheumatoid arthritis (RA), ankylosing spondylitis, plaque psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s Disease.
Subcutaneous injection
Trial or other data
Sep 21Alvotech report positive results from PIII NCT04453137 (n=568) switching study. Repeated switches between Humira and AVT02 was found to be bioequivalent to administration of Humira without switching, with no significant differences observed in clinical efficacy, safety and immunogenicity [no specific results reported] [9].
Jun 20PIII trial (n=413) in moderate-severe psoriasis NCT03849404 comparing AVT02 with Humira due to complete June 20 [3].
May 20Alvotech reported that the phase III trial (NCT03849404, n=412) met its primary endpoint of demonstrating equivalent efficacy as measured by the Psoriasis Area and Severity Index (PASI) percent improvement at week 16 [4].
Aug 19PIII trials ongoing are Eudra-CT2017-003367-35 and NCT03579823.
Evidence based evaluations
Hyrimoz Psoriasis and other Humira indications - new 100mg/mL citrate-free formulation
Information
Hyrimoz
New formulation
Sandoz
Sandoz
Development and Regulatory status
None
Pre-registration (Filed)
None
Jun 22EMA accepts an application for a high-concentration, 100mg/mL formulation of Hyrimoz for regulatory review [2].
Category
Tumour necrosis factor alpha (TNF-α) inhibitor. Available as a 100mg/mL formulation, free from the excipient citrate and uses the same autoinjector as the 50mg/mL version of Hyrimoz.
The prevalence of psoriasis is estimated to be about 1.3-2.2% in the UK, with the highest prevalence being in white people. Men and women are equally affected. It can occur at any age but the majority of cases first present before the age of 35 years. It is uncommon in children. Plaque psoriasis accounts for 90% of all people with psoriasis [1].
Psoriasis and other Humira indications - new 100mg/mL citrate-free formulation
Subcutaneous injection
Trial or other data
Jun 22Sandoz submits data to the EMA from a phase 1 pharmacokinetic bridging study that compared the 50mg/mL and 100mg/mL versions of Hyrimoz. The study showed the new formulation has comparable pharmacokinetics and similar safety and immunogenicity to its lower-concentration predecessor [2].
Amsparity (EU), Abrilada (US) Rheumatoid arthritis (RA) and other Humira indications
Information
Amsparity (EU), Abrilada (US)
Biosimilar
Pfizer
Pfizer
Development and Regulatory status
Licensed but not launched
Licensed but not launched
Approved (Licensed)
Mar 22The patents on Humira expired in Europe in June 2017. However, in the US AbbVie has stated that although the composition of matter patent covering Humira expired in December 2016, non-composition of matter patents covering Humira expire no earlier than 2022. The company has therefore made settlement agreements with eight companies delaying the launch of biosimilars in the US until January 2023 [15]
Feb 22FDA accepts for review the Prior approval Supplement (PAS) to the BLA for for Abrilada (adalimumab-afzb) as an interchangeable biosimilar to Humira (adalimumab). If approved as interchangeable, Abrilada will be the second interchangeable adalimumab biosimilar. Cyltezo (adalimumab-adbm) was approved as interchangeable in Oct 21 [15]
Aug 20Pfizer currently has no plans to launch Amsparity in the EU [14].
Feb 20Approved in EU [13].
Jan 20Has received approval is US as Abrilada [12].
Dec 19Has also been filed in the US [11].
Dec 19The proposed indications for Amsparity include rheumatoid arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis, paediatric plaque psoriasis, hidradenitis suppurativa, Crohn´s disease, paediatric Crohn´s disease, ulcerative colitis, uveitis, paediatric uveitis (although not for all strengths). Amsparity will be available as a solution for injection (40mg in a pre-filled syringe and pre-filled pen and, for paediatric use only, 20mg in a pre-filled syringe and 40mg/0.8 ml in a vial) [10].
Dec 19Recommended for EU approval by CHMP as Amsparity, for the full indications of the reference product (Humira) [10].
Dec 18The application under the brand name Fyzoclad incorporated a subset of indications; a further application including the full spectrum of indications remains under review [9].
Dec 18Pfizer have withdrawn their EU Marketing Authorisation Application during the early stages of its assessment by CHMP: the reason given by the company is a change of strategy, although they reserve the right ro re-submit an application in future [8].
Category
A biosimilar version of adalimumab, a humanised recombinant monoclonal IgG1 antibody targeting tumour necrosis factor (TNF)-α.
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
Rheumatoid arthritis (RA) and other Humira indications
Subcutaneous
Trial or other data
Jan 17Pfizer announce REFLECTIONS B538-02 trial (NCT02480153) met its primary endpoint by demonstrating that the efficacy of PF-06410293 was equivalent to Humira as measured by ACR20 response rate at week 12 in patients with moderate to severe rheumatoid arthritis [6].
Jan 17Estimated completion date for REFLECTIONS B538-02 trial (NCT02480153) is Dec 17 [5].
Oct 14PIII study initiated to compare adalimumab biosimilar and adalimumab (Humira®) in combination with methotrexate in moderate to severe RA, who showed inadequate response to the treatment with methotrexate (REFLECTIONS B538-02; EudraCT2014-000352-29). Enrolment is underway in Lithuania and Spain, and is expected to expand to other sites in the EU, Canada, Australia, South America and Asia [3]
Oct 13NCT01870986 (REFLECTIONS) is a PI double-blind, randomized, parallel-group, single-dose, 3-arm study comparing pharmacokinetics of PF-06410293 and adalimumab sourced from the US and EU administered to healthy volunteers. The main objective is to demonstrate equivalent pharmacokinetic properties – maximum observed serum concentration (Cmax), area under the curve from time zero to last quantifiable concentration (AUCt) and AUC from time zero extrapolated to infinity (AUC¥) over a period of 43 days. The trial will include 210 healthy adults, aged 18–55 years. It started Jun 13 and is expected to be completed in Feb 2014 [1]
Evidence based evaluations
Yusimry (US)Psoriasis and other Humira indications
Information
Yusimry (US)
Biosimilar
Coherus Biosciences
Coherus Biosciences
Development and Regulatory status
Phase III Clinical Trials
Phase III Clinical Trials
Approved (Licensed)
Dec 21FDA approves YUSIMRY™ , a adalimumab biosimilar product. YUSIMRY is indicated for plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, Crohn’s disease, and ulcerative colitis [12]
Feb 21Coherus does not describe any plans for commercialisation of CHS-1420 in any markets outside the US; assume no plans to make CHS-1420 available in the UK. If approved by the FDA, it plans to launch CHS-1420 in the US on or after July 1, 2023 [10, 11].
Feb 21The FDA has accepted CHS-1420 for review, and has set a Biosimilar User Fee Act action date for December 2021 [8].
Jun 20Focus on securing competitive launch of CHS-1420 in US market [7].
Aug 18CHS-1420 is available for global licensing [5]; the company is focussed on competitive launch in the US [6].
Mar 18Coherus BioSciences intends to launch the product in 2022 [4]
Dec 14Coherus BioSciences reported its plan to start PIII clinical development the first half of 2015 [2]
Category
A biosimilar version of adalimumab, a humanised recombinant monoclonal IgG1 antibody targeting tumour necrosis factor (TNF)-α.
Psoriasis and other Humira indications
Subcutaneous injection
Trial or other data
Aug 17Positive results for clinical pharmacokinetic bioequivalence study for CHS-1420 vs. Humira in healthy subjects announced. This single-blind, single dose study (n=216) reports 90% confidence intervals of the geometric mean ratios for all pharmacokinetic endpoints fell within the bioequivalence boundaries of 80-125%. No clinically meaningful differential adverse events observed between the 2 agents [3].
Jan 17PIII study met its primary endpoint demonstrating similarity between CHS-1420 and Humira in patients achieving 75% improvement in psoriasis area and severity index (PASI-75). At Week 16, 80.3% of subjects in the CHS-1420 group and 77.5% of subjects in the Humira group achieved PASI-75. In weeks 16-24, half of the subjects who were initially treated with Humira were switched to CHS-1420. PASI-75 was similar across the 3 subsequent treatment groups, CHS-1420 followed by CHS-1420, Humira followed by CHS-1420, and Humira followed by Humira. CHS-1420 and Humira were similarly well tolerated in all groups during Part 2. Anti-drug antibody results are preliminary but have not identified any clinically significant differences between treatments [9].
Aug 14In a pivotal single-dose clinical pharmacokinetic study in healthy subjects vs. Humira, CHS-1420 met the criteria for similarity on three endpoints: maximum serum concentration (Cmax), area under the time-concentration curve from first to last time point measured (AUC0-t), and area under the time-concentration curve from first time point extrapolated to infinity (AUC0-inf) [1]