Rituximab

Refrigerated StorageLactation Safety InformationNew Medicines ·
108809004

Refrigerated Storage

MabTheraRoche Products Ltd

Roche Products Ltd
MabThera
Injection, 100mg and 500mg concentrate for solution for infusion and 1400mg solution for subcutaneous injection

Contact Roche in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.

Storage at ambient temperature: not provided by manufacturer.

Keep the container in the outer carton in order to protect from light.

28 September 2020
London MI Service

TruximaNapp Pharmaceuticals Limited

Napp Pharmaceuticals Limited
Truxima
Concentrate for solution for infusion, 100mg and 500mg

In the event of an inadvertent temperature excursion the following data may be used:

For 100mg vials, in-house stability data from the manufacturers have shown that the unopened vials may be kept up to 25°C for 1 month.

For 500mg vials, in-house stability from the manufacturers have shown that the unopened vial may be kept up to 25°C for 2 months.

 

Yes - as per the information above.
Yes
14 May 2020
London Medicines Information Service

RixathonSandoz Limited

Sandoz Limited
Rixathon
Injection, 100mg and 500mg concentrate for solution for infusion

Contact Sandoz in all cases where a deviation from the recommended storage conditions has occurred.

Refer to the current BNF for company contact details.

Storage at ambient temperature: not provided by manufacturer.

Keep the container in the outer carton in order to protect from light.

28 September 2020
London Medicines Information Service

Lactation Safety Information

for lymphoma/CLL

for lymphoma/CLL
-
Limited published evidence of safety indicates small amounts in breast milk which are likely to be degraded in infants GI tract
Long half-life increases risk of accumulation in breastfed infants
Infants should be monitored for signs of infection and immunosuppression
Although large protein molecules may appear in colostrum, risk to preterm infants and neonates is considered to be small and unproven
16 August 2020

for rheumatoid arthritis

for rheumatoid arthritis
See summary
Limited published evidence of safety indicates small amounts in breast milk which are likely to be degraded in infants GI tract
Long half-life increases risk of accumulation in breastfed infant
Although large protein molecules may appear in colostrum, risk to preterm infants and neonates is considered to be small and unproven
16 August 2020

New Medicines

MabThera (EU), Rituxan (US)Diffuse large B-cell lymphoma (DLBCL), Burkitt's lymphoma/leukaemia (BL) and Burkitt-like lymphoma (BLL), and severe, active GPA (Wegener’s) and MPA; paediatric patients

Information

MabThera (EU), Rituxan (US)
Licence extension / variation
Roche
Roche

Development and Regulatory status

Launched
Launched
Launched
March 2020
Mar 20Already licensed in US for treatment of GPA and MPA in children from the age of 2 years, but not for cancer in children [4].
Mar 20New indications approved in EU [3].
Jan 20EU positive opinion for two new indications for MabThera - 1. Use in combination with glucocorticoids for induction of remission in paediatric patients (aged ≥2 to <18 years old) with severe, active granulomatosis with polyangiitis (Wegener’s) (GPA) and microscopic polyangiitis (MPA); 2. Use in combination with chemotherapy for treatment of paediatric patients (aged ≥6 months to <18 years old) with previously untreated advanced stage CD20 positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL)/Burkitt leukaemia (mature B-cell acute leukaemia) (BAL) or Burkitt-like lymphoma (BLL) [2].

Category

B cell inhibitor, CD20 antigen inhibitor
Burkitt lymphoma most commonly affects children but can occur in adults. Burkitt and Burkitt-like lymphomas account for fewer than 10% of adult diffuse lymphomas but account for the majority of childhood B-cell lymphomas. It is significantly more common in sub-Saharan Africa [1].
Diffuse large B-cell lymphoma (DLBCL), Burkitt's lymphoma/leukaemia (BL) and Burkitt-like lymphoma (BLL), and severe, active GPA (Wegener’s) and MPA; paediatric patients
Intravenous

Evidence based evaluations

RuxienceRheumatoid arthritis (RA) and pemphigus vulgaris

Information

Ruxience
Biosimilar
Pfizer
Pfizer

Development and Regulatory status

Launched
Launched
Phase III Clinical Trials
July 2020
Jul 20Available in the UK. 10mg/ml conc for soln for inf in vial, 10ml=£157.17; 50ml=£785.84 [10].
Apr 20Approved in EU for treatment of RA and PV [9].
Jan 20Recommended for approval in EU for treatment of adults with rheumatoid arthritis and pemphigus vulgaris [8].
Mar 19Currently pre-registration in EU [6].

Category

Biosimilar. Rituximab is a chimeric mouse-human monoclonal antibody that targets and binds to the CD20 antigen, a cell surface marker that is widely expressed on the surface of B-cells.
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.
Rheumatoid arthritis (RA) and pemphigus vulgaris
Intravenous infusion

Trial or other data

Sep 16Results of NCT01526057 (REFLECTIONS B328-01) published. Study of 214 patients found no clinically meaningful difference in DAS28 or ACR response at 24 weeks between PF-05280586, rituximab sourced from the EU and rituximab sourced from the US. The differences were within the pre-specified ranges [5].
Oct 15REFLECTIONS B328-04 is still on-going and is expected to complete collection of primary outcome data in Mar 16 [4].
Mar 15REFLECTIONS B328-01 has completed and REFLECTIONS B328-04 is on-going but is fully recruited [2]
Jun 13NCT01643928 (REFLECTIONS B328-04) this extension study will evaluate the safety and immunogenicity of treatment with rituximab-Pfizer, including that after transitioning from rituximab-US or rituximab-EU to rituximab-Pfizer. This study will provide continued treatment access to subjects with active rheumatoid arthritis who have participated for at least 16 weeks in other studies in the rituximab-Pfizer program. The study will enroll 157 subjects who will receive rituximab-Pfizer on days 1 and 15 of each 24 week treatment course for up to 3 courses or rituximab-US or rituximab-EU for 1 course and rituximab Pfizer for up to an additional two treatment courses. It started Aug 12 and is due to complete Aug 15 [1].
Jun 13NCT01526057 (REFLECTIONS B328-01) is a PI/II randomized, double-blind, 3-arm study comparing the pharmacokinetics and pharmacodynamics, and assessing the safety of PF-05280586 and US- and EU-sourced rituximab (1000mg, IV on days 1 and 15) in 210 subjects with active rheumatoid arthritis on a background of methotrexate who have had an inadequate response to one or more TNF antagonist therapies. The primary outcomes are Cmax `nd AUC 0-infinity at week 25. The study started Mar 12 and is due to complete Jun 14 [1].

RuxienceFollicular lymphoma and all licensed cancer (and NHSE commissioned) indications of originator product

Information

Ruxience
Biosimilar
Pfizer
Pfizer

Development and Regulatory status

Launched
Launched
Approved (Licensed)
July 2020
Jul 20Available in the UK. 10mg/ml conc for soln for inf in vial, 10ml=£157.17; 50ml=£785.84 [13].
Apr 20Approved in EU for treatment of NHL, CLL, GPA and MPA [12].
Jan 20Recommended for approval in the EU for treatment of NHL, CLL, GPA and MPA [11].
Jul 19Approved in US for the treatment of adult patients with non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), and granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) [10].
Mar 19Currently pre-registration in EU [9].
Sep 18Filed in US for follicular lymphoma with the BsUFA goal date for a decision by the FDA in Q2 2019 [6,7].
Oct 15PIII development continues [3].
Sep 14PIII [1].

Category

A biosimilar version of rituximab, designated PF-05280586. Rituximab is a chimeric mouse-human monoclonal antibody that targets and binds to the CD20 antigen, a cell surface marker that is widely expressed on the surface of B-cells.
The UK incidence of NHL is about 18 per 100,000 people. Around 22% of people have follicular disease (4 per 100,000).
Follicular lymphoma and all licensed cancer (and NHSE commissioned) indications of originator product
Intravenous infusion

Trial or other data

Feb 19PIII trial (B328-06, NCT02213263) with subjects randomized to PF‑05280586 (n = 196) or rituximab‑EU (Mabthera, n = 198). No meaningful difference in efficacy between PF‑05280586 and MabThera was identified. ORR at Week 26 was 75.5% for PF‑05280586 and 70.7% for rituximab-EU, within the pre-specified equivalence margin of ±16% (FDA and EMA´s regulatory agreed limit). Estimated rates of one-year progression-free survival were similar across both groups (76.4% PF‑05280586 vs 81.2% MabThera)[8].
Jan 18Pfizer announces positive top-line results from comparative REFLECTIONS B3281006 study. PF-05280586 demonstrated equivalence to MabThera® in overall response rate (no absolute results reported) [5].
Jan 17PIII trial comparing PF-05280586 with rituximab in low tumour burden follicular lymphoma (NCT02213263) due to complete Jun 2018 [4].
Dec 14NCT02213262 = REFLECTIONS B328-06 [2].
Sep 14PIII (NCT02213263) study begins recruitment of 394 patients with CD20-positive, low tumor burden follicular lymphoma to assess safety and effectiveness of PF-05280586 versus rituximab-EU. The primary hypothesis to be tested in this study is that the effectiveness of PF-05280586, as measured by the Overall Response Rate, is similar to that of rituximab-EU. Study sites include the US & EU (but not UK). The study is expected to complete collection of primary outcome data in Nov 16 [2].

rituximab biosimilar (MabionCD20)Non-Hodgkin lymphoma (NHL)

Information

rituximab biosimilar (MabionCD20)
Biosimilar
Mylan UK
Not Known

Development and Regulatory status

Filing withdrawn
Filing withdrawn
None
Apr 20Mabion signed an agreement with US-based drugmaker Mylan to commercialize MabionCD20 in the European Union (EU) and non-EU Balkan states in November 2016 [1]. Then the company submitted its first application of MabionCD20 to the European Medicines Agency (EMA) for approval in June 2018 [2]. Then on 6 August 2018, Mabion received permission from EMA to submit a second, or duplicate, application for MabionCD20. The second application was submitted in order to acquire an additional trade name, for which the list of indications for the product would be limited and would not include rheumatoid arthritis (RA). This, according to the company, could accelerate the commercialization of MabionCD20 in markets where RA is still covered by the patent protection for MabThera. However, on 16 April 2020, Mabion withdrew the applications. This decision was taken by the company after EMA ‘had evaluated the information from the company and prepared questions’. EMA said that after it had ‘assessed the company’s responses to the last round of questions, there were still some unresolved issues’. Based on the review of the data and the company’s response to EMA’s questions, at the time of the withdrawal, the agency still ‘had some concerns and its provisional opinion was that Rituximab Mabion could not have been authorized for the requested indications’. EMA said that it ‘was concerned that biosimilarity between Rituximab Mabion and the reference medicine MabThera had not been established’. In addition, EMA said that it ‘also had concerns about the manufacturing process and the system for ensuring reliable quality of the medicine’. Therefore, at the time of the withdrawal, EMA’s ‘opinion was that the company had not fully addressed its concerns and therefore the benefit of Rituximab Mabion could not be established’. Despite the rejection by EMA, Mabion said in its letter notifying EMA of the withdrawal of the applications that the applications ‘pertained only to the initial scale of manufacturing process’ and that they ‘will prepare a new application’ [9].
Mar 20Mabion has withdrawn its application for EU marketing authorisation - further details will be published later [8].
Jun 18Filed in EU using the centralised authorisation procedure. The application is based on data from trials conducted on patients with rheumatoid arthritis and non-Hodgkin´s lymphoma. Mabion has an upcoming meeting with the US FDA to finalise the most optimal pathway towards registering MabionCD20 in the US [7].
Jan 17Mylan has reached an agreement with Mabion for the exclusive right to commercialise their rituximab biosimilar in the EU [7].

Category

Chimeric monoclonal antibody against CD20 protein on B-lymphocytes.
2.4 in 10,000 people in the EU have diffuse large B-cell lymphoma, equivalent to around 123,000 people [3].
Non-Hodgkin lymphoma (NHL)
Intravenous

Trial or other data

Jan 18PIII trial (NCT02617485) completes [10].
May 16PIII trial in DBCL (NCT02617485) due to complete June 2017 [5].
Nov 15Mabion is planning a PIII trial in DBCL in Bosnia and Herzegovina, Croatia, Georgia, Hungary, Moldova, Poland, Romania, Serbia and Ukraine (NCT02617485) [4].
Mar 15PIII study end points include pharmacokinetic endpoints, efficacy, comparative safety and immunogenicity [1].
Sep 14Sep 14: PIII study initiated to evaluate the bioequivalence of Mabion´s rituximab biosimilar compared with Roche´s rituximab (MabThera®), in patients with diffuse large B-cell lymphoma (EudraCT2013-005506-56). The study is expected to enrol approximately 140 subjects; recruitment is underway in Croatia and is expected to expand to Bosnia, Herzegovina, Bulgaria, Georgia, Hungary, Republic of Moldova, Poland and Serbia [2].

rituximab biosimilar (MabionCD20)Rheumatoid arthritis (RA)

Information

rituximab biosimilar (MabionCD20)
Biosimilar
Mylan UK
Not Known

Development and Regulatory status

Filing withdrawn
Filing withdrawn
None
Apr 20Mabion signed an agreement with US-based drugmaker Mylan to commercialize MabionCD20 in the European Union (EU) and non-EU Balkan states in November 2016 [1]. Then the company submitted its first application of MabionCD20 to the European Medicines Agency (EMA) for approval in June 2018 [2]. Then on 6 August 2018, Mabion received permission from EMA to submit a second, or duplicate, application for MabionCD20. The second application was submitted in order to acquire an additional trade name, for which the list of indications for the product would be limited and would not include rheumatoid arthritis (RA). This, according to the company, could accelerate the commercialization of MabionCD20 in markets where RA is still covered by the patent protection for MabThera. However, on 16 April 2020, Mabion withdrew the applications. This decision was taken by the company after EMA ‘had evaluated the information from the company and prepared questions’. EMA said that after it had ‘assessed the company’s responses to the last round of questions, there were still some unresolved issues’. Based on the review of the data and the company’s response to EMA’s questions, at the time of the withdrawal, the agency still ‘had some concerns and its provisional opinion was that Rituximab Mabion could not have been authorized for the requested indications’. EMA said that it ‘was concerned that biosimilarity between Rituximab Mabion and the reference medicine MabThera had not been established’. In addition, EMA said that it ‘also had concerns about the manufacturing process and the system for ensuring reliable quality of the medicine’. Therefore, at the time of the withdrawal, EMA’s ‘opinion was that the company had not fully addressed its concerns and therefore the benefit of Rituximab Mabion could not be established’. Despite the rejection by EMA, Mabion said in its letter notifying EMA of the withdrawal of the applications that the applications ‘pertained only to the initial scale of manufacturing process’ and that they ‘will prepare a new application’ [8].
Mar 20Mabion has withdrawn its application for EU marketing authorisation - further details will be published later [7].
Jun 18Filed in EU using the centralised authorisation procedure. The application is based on data from trials conducted on patients with rheumatoid arthritis and non-Hodgkin´s lymphoma. Mabion has an upcoming meeting with the US FDA to finalise the most optimal pathway towards registering MabionCD20 in the US [6].
Jan 17Mylan has reached an agreement with Mabion for the exclusive right to commercialise their rituximab biosimilar in the EU [4].

Category

Chimeric monoclonal antibody against CD20 protein on B-lymphocytes.
The incidence of RA is low, with around 1.5 men and 3.6 women developing the condition per 10,000 people per year. The disease affects around 400,000 people in the UK, of whom approximately 15% have severe disease.
Rheumatoid arthritis (RA)
Intravenous

Trial or other data

Dec 20PIII MABRIDGE trial will aim to establish a 3-way PK similarity bridge between MabionCD20 , US-licensed Rituxan and EU approved MabThera, based on PK comparison. The main study objective is to demonstrate therapeutic similarity between MabionCD20 and registered EU- and US-rituximab. Patients with active moderate-to-severe rheumatoid arthritis diagnosed according to the 2010 ACR criteria will be randomized to receive treatment with stable methotrexate therapy with either MabionCD20, MabThera or Rituxan. Patients will be followed for a minimum of 24 weeks to establish pharmacokinetic and clinical similarity and to compare PD, safety and immunogenicity parameters between the three rituximab products. 210 adults will be recruited (sites yet to be announced). Collection of primary outcome data is due to complete Jun 22 [10].
Dec 20Mabion plans to start the PIII MABRIDGE (NCT04680962) in March 21 [9].
Jan 18No recent progress on NCT02468791 [5].
Jan 17No update available on progress of PIII (NCT02468791) study [3].
Jan 16The PIII study is registered on clinicaltrials.gov (NCT02468791) with an estimated enrollment of 863 patients and a completion date of Dec 16 [3].
Feb 13Mabion commences a PIII clinical trial to investigate the bioequivalence in terms of pharmacokinetics and efficacy of two different rituximab formulations in patients with rheumatoid arthritis. The primary endpoint is the peak drug concentration after the second infusion cycle, the area under the plasma concentration-time curve from the first administration to final time point at Week 24 and the percentage of patients achieving an American College of Rheumatology 20% response criteria score at week 24. Approximately 863 patients are expected to enrol in Georgia, Lithuania, Poland, Romania, Russia, Serbia, and Ukraine. Enrolment has commenced in Lithuania with other centres to follow (EudraCT2012-003194-25) [2]

RiabniNon-Hodgkin lymphoma (NHL) chronic lymphocytic leukaemia, granulomatosis with polyangiitis and microscopic polyangiitis

Information

Riabni
Biosimilar
Amgen
Amgen

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Jan 21Amgen currently has no plans to apply for a licence for Riabni in the UK [13].
Dec 20The US licence application for Riabni sought approval for treatment of the following indications for which US Rituxan has previously been approved: adult CLL, adult NHL, adult GPA and adult MPA. Amgen did not seek approval for treatment of GPA/MPA in children [12].
Dec 20The Wholesale Acquisition Cost (list price) of Riabni in the US will be 23.7% lower than the reference product, Rituxan. List price $716.80 per 100 mg and $3,584.00 per 500 mg single-dose vial, 23.7% less than the WAC for Rituxan, which is 15.2% less than the WAC for Truxima® (biosimilar to Rituxan) and matching the WAC for Ruxience® (biosimilar to Rituxan). At launch, Riabni will be priced 16.7% below the current Rituxan Average Selling Price [11].
Dec 20Also approved in the US to treat granulomatosis with polyangiitis (GPA) (Wegener´s granulomatosis) and microscopic polyangiitis (MPA). Riabni will be made available in the US in January 2021 [11].
Dec 20Registered in US for NHL and CLL [10]
Dec 19ABP 798 has been successfully submitted to the US Food and Drug Administration (FDA) for review [10].
Oct 16No new information available on development progress in Amgen pipeline [4].
Nov 15Development continues [3].

Category

A biosimilar version of rituximab, designated ABP 798. Rituximab is a chimeric mouse-human monoclonal antibody that targets and binds to the CD20 antigen, a cell surface marker that is widely expressed on the surface of B-cells.
The UK incidence of NHL is about 18 per 100,000 people and 40-50% have indolent (low-grade) disease, usually advanced at presentation.
Non-Hodgkin lymphoma (NHL) chronic lymphocytic leukaemia, granulomatosis with polyangiitis and microscopic polyangiitis
Intravenous infusion

Trial or other data

Sep 19PIII trial NCT02747043 comparing ABP798 with Rituxan found the overall response rate (ORR) by week 28, was within the prespecified margin, showing clinical equivalence. Safety and immunogenicity of the two were comparable [8].
Jan 19PIII trial NCT02747043 is active, not recruiting [7].
Mar 18PIII trial still recruiting [6].
Nov 16PIII trial to compare ABP798 with licensed rituximab, in patients with CD 20 positive B-cell non Hodgkin lymphoma (NCT027470430), now recruiting with estimated primary completion date March 2018 [5].
Dec 14 A PIII trial designed to assess efficacy, safety and immunogenicity of biosimilar rituximab in 250 patients with CD20 positive B-Cell Non-Hodgkin Lymphoma (NHL) initiated(20130109; EudraCT2013-005542-11). Recruitment has been initiated in Spain and is expected to expand to other countries [2].

Evidence based evaluations

RiabniRheumatoid arthritis (RA) and pemphigus vulgaris in adults

Information

Riabni
Biosimilar
Amgen
Amgen

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

A biosimilar version of rituximab, designated ABP 798. Rituximab is a chimeric mouse-human monoclonal antibody that targets and binds to the CD20 antigen, a cell surface marker that is widely expressed on the surface of B-cells.
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.
Rheumatoid arthritis (RA) and pemphigus vulgaris in adults
Intravenous infusion