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704316006

New Medicines

XeljanzRheumatoid arthritis (RA) and psoriatic arthritis - modified-release once-daily formulation

Information

Xeljanz
New formulation
Pfizer
Pfizer

Development and Regulatory status

Launched
Launched
Launched
February 2020
Sep 21MHRA approves a licence extension for Xeljanz 11mg prolonged-release tablets, to allow use in combination with methotrexate for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug therapy [10].
Jul 21EMA approves a licence extension for Xeljanz 11mg prolonged-release tablets, to allow use in combination with methotrexate for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug therapy [11].
Feb 20Available in the UK. Price 1x28 tablet pack = £690.03 [7,8].
Dec 19Xeljanz 11mg prolonged-release tablets approved in EU [5,6].
Oct 19EU positive opinion for Xeljanz 11mg prolonged-release tablets for use in combination with methotrexate (MTX) for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs. Tofacitinib can be given as monotherapy in case of intolerance to MTX or when treatment with MTX is inappropriate [6].
May 18Filed in EU [3].
Feb 16US FDA approves XELJANZ® XR (tofacitinib citrate) extended-release 11 mg tablets for the once-daily treatment of moderate to severe RA in patients who have had an inadequate response or intolerance to MTX [2].

Category

Janus kinase (JAK) 3 inhibitor - once daily, modified-release 11mg formulation
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 [1].
Rheumatoid arthritis (RA) and psoriatic arthritis - modified-release once-daily formulation
Oral

Trial or other data

Jan 21Tofacitinib fails to meet co-primary endpoints in PIV safety study (NCT02092467, n=4362). The primary objective was to evaluate safety of tofacitinib at two doses (5 or 10 mg BD) vs. adalimumab or etanercept in RA pts (≥50 years + at least 1 additional cardiovascular risk factor). For tofacitinib, the most frequently reported major adverse cardiovascular events was myocardial infarction and the most frequently reported malignancy was lung cancer. [9]
Jun 19Pfizer announce positive results from PIIIb/IV randomised, double-blind, placebo-controlled study, ORAL Shift (NCT02831855), in adult patients (n=694) with moderately to severely active rheumatoid arthritis (RA). Patients who achieved low disease activity (LDA) with Xeljanz XR 11 mg once daily plus methotrexate (MTX) after a 24-week open-label run-in period, were randomised to evaluate the efficacy and safety of Xeljanz XR as monotherapy after MTX withdrawal vs Xeljanz XR with continued MTX. The study demonstrated non-inferiority of MTX withdrawal with Xeljanz XR vs Xeljanz XR plus MTX at week 48 as measured by the primary endpoint, the change in the Disease Activity Score (DAS28-4[ESR]) from randomisation at week 24 to the end of the double-blind MTX withdrawal phase at week 48. The study results will be presented at the Annual European Congress of Rheumatology (EULAR 2019) in Spain [4].

Evidence based evaluations

XeljanzPolyarticular juvenile idiopathic arthritis and juvenile psoriatic arthritis - and new oral solution formulation

Information

Xeljanz
Licence extension / variation and new formulation
Pfizer
Pfizer

Development and Regulatory status

Launched
Launched
Launched
Oct 211 mg/mL oral solution (new formulation) approved in UK with same indication as 5mg tablets [14].
Oct 215mg tablets approved in UK for "the treatment of active polyarticular juvenile idiopathic arthritis (rheumatoid factor positive [RF+] or negative [RF-] polyarthritis and extended oligoarthritis), and juvenile psoriatic arthritis (PsA) in patients 2 years of age and older, who have responded inadequately to previous therapy with DMARDs" [13].
Aug 21EMA approves licence extension for tofacitinib and approves a new pharmaceutical form (oral solution, 1mg/ml)[12].
Jun 21Extension to existing indication recommended for EU approval by CHMP – the new indication is “Tofacitinib is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (rheumatoid factor positive or negative polyarthritis and extended oligoarthritis), and juvenile psoriatic arthritis (PsA) in patients 2 years of age and older, who have responded inadequately to previous therapy with DMARDs. Tofacitinib can be given in combination with methotrexate (MTX) or as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate [11].
Jan 21Is currently pre-registration in the EU, having been filed using the centralised procedure [10].
Sep 20Approved in US for treatment of children and adolescents 2 years and older with active polyarticular course juvenile idiopathic arthritis (pcJIA). Two formulations were approved, a tablet and an oral solution, and are dosed based upon weight. Xeljanz oral solution is anticipated to be available by the end of Q1 2021. Xeljanz 5 mg tablets are available immediately [10].

Category

Janus kinase (JAK) 3 inhibitor. Tablets and oral solution.
The prevalence is estimated to be 1-2 per 1,000 children [3].
Polyarticular juvenile idiopathic arthritis and juvenile psoriatic arthritis - and new oral solution formulation
Oral

Further information

Yes

Trial or other data

Feb 20PIII NCT02592434 study meets primary outcome showing that in patients with pcJIA who achieved a JIA ACR 30 response at the end of the run-in phase, the occurrence of disease flare in patients treated with tofacitinib (27/88) was statistically significantly (p=0.0007) lower than patients treated with placebo (47/85) at week 44 [9].
May 19PIII NCT02592434 study completes [8].
Dec 18PIII study (NCT02592434) to evaluate efficacy, safety and tolerability of tofacitinib in pediatric JIA patients is recruiting. This is a randomized withdrawal, double blind, placebo controlled study of 210 pediatric subjects (2 to <18 years of age) with JIA. The primary objective is to compare the efficacy of tofacitinib versus placebo for the treatment of signs and symptoms of JIA at Week 26 of the double blind phase as measured by the percentage of subjects with disease flare (according to PRCSG/PRINTO Disease Flare criteria) after Week 18 of the open label run in phase.All eligible subjects enrolled in the study will initially receive open label tofacitinib for 18 weeks (run in phase). At the end of the 18 week run in phase, only subjects who achieve at least a JIA ACR 30 response will be randomized to the 26 week double blind, placebo controlled phase. Subjects who do not achieve a JIA ACR 30 response at this time point will be discontinued from the study. In addition, subjects who experience a single episode of disease flare at any time during the study (including the open label run in and double blind phase) will also be discontinued from the study. All subjects participating in this study, including those discontinued from the study, will have the option, if eligible (based on inclusion and exclusion criteria), of enrolling in the tofacitinib JIA long term extension study (A3921145; NCT01500551). Collection of primary outcome data is due to complete May 19 [7].
Sep 17NCT01500551 now estimated to complete March 2021 [7].
Feb 15PIII NCT01500551 study is currently recruiting patients [5].
Apr 14Estimated study completion date Sep 2020. [5]
Jan 13Phase II/III clinical trial initiated to evaluate the long-term tolerability of tofacitinib in patients with juvenile idiopathic arthritis (juvenile rheumatoid arthritis) (NCT01500551). [4]
Apr 12Pfizer is planning to initiate a phase II/III clinical trial to evaluate the long-term tolerability of tofacitinib in patients with juvenile rheumatoid arthritis (NCT01500551). This trial is scheduled to begin in May 2012. [2]
Jan 11NCT01500551 A PII/PIII long-term, open-label follow-up study in 290 subjects (aged 2-18 years) with juvenile idiopathic arthritis (JIA). The primary outcome is standard laboratory safety data and adverse event (AE) reports including body weight, height and Tanner Stages collected for up tp 8 years. The study will start May 12 and is due to complete Aug 19 [1].

Evidence based evaluations

XeljanzAnkylosing spondylitis (AS) in adults who have responded inadequately to conventional therapy

Information

Xeljanz
Licence extension / variation
Pfizer
Pfizer

Development and Regulatory status

None
Recommended for approval (Positive opinion)
Pre-registration (Filed)
Oct 21Recommended for EU approval by CHMP – the additional indication is “for the treatment of adult patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy” [9].
Jul 21Pfizer announce that FDA will not meet the PDUFA goal date for tofacitinib due to ongoing review of the Pfizer post-marketing safety study evaluating tofacitinib in RA. Pfizer remain confident in the benefit-risk profile. The FDA had previously updated the PDUFA goal date to Q3 2021, no further update to dates has been provided [8].
May 21Is pre-registration in the EU [7].
Oct 20Has been filed in the US [5].
Jan 20PIII (NCT03502616) active but not recruiting. Primary completion date December 2019 [3].

Category

Janus kinase (JAK) 3 inhibitor.
Prevalence is 0.1-2% of the general population, with the highest prevalence in northern European countries and the lowest in people of Afro-Caribbean descent [1].
Ankylosing spondylitis (AS) in adults who have responded inadequately to conventional therapy
Oral

Further information

Yes

Trial or other data

May 21NCT03502616 RCT (n=269) is published; it found a significantly improved ASAS20 response for tofacitinib vs placebo at week 16 (56.4% vs 29.4%, p<0.0001). The ASAS40 response was also superior (40.6% vs 12.5%, p<0.0001). Authors state no new potential safety risks for tofacitinib were identified [6].
Nov 20PIII trial ASAS (n=270) met primary endpoint showing that at week 16, the percentage of patients achieving an ASAS20 response was significantly greater with tofacitinib (56.4%) versus placebo (29.4%) (p<0.0001). In addition, ASAS40 response was significantly greater with tofacitinib versus placebo (40.6% vs12.5%, p<0.0001), a secondary endpoint [4].
Feb 19PIII study (NCT03502616) is recruiting [2].
Jun 18PIII study (NCT03502616) to determine if tofacitinib is safe and effective in subjects with active ankylosing spondylitis starts. 240 adults will be recruited from countries including the US & EU (but not UK). Collection of primary outcome data (Assessment in Ankylosing Spondylitis (ASAS) 20 response at week 16) is due to complete Aug 20 [2].

Evidence based evaluations