dm+d

38030311000001103

New Medicines

RinvoqModerate to severe psoriatic arthritis - second-line

Information

Rinvoq
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

Launched
Launched
Launched
January 2021
Dec 21Rinvoq approved by US FDA for treatment of adults with active psoriatic arthritis who have had an inadequate response or demonstrated an intolerance to >1 TNF blockers. Approval was based on data from 2 PIII studies, SELECT-PsA 1 and SELECT-PsA 2. [10]
Jun 21Decision on US licence application further delayed due to the ongoing review into FDA safety concerns for JAK inhibitors as a class [9]
Mar 21AbbVie announces extension of FDA review. The updated Prescription Drug User Fee Act (PDUFA) action date has been extended three months to late Q2 2021 [7].
Jan 21Licence extension also approved in UK [6].
Jan 21Approved in EU [5].
Dec 20Recommended for EU approval by CHMP - the additional indication is "for the treatment of active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs. Rinvoq may be used as monotherapy or in combination with methotrexate" [4].
Jun 20Filed in EU via centralised procedure and in US [4].

Category

Janus kinase inhibitor
Prevalence varies from 20-420 per 100,000 population across the world, except in Japan where it is 1 per 100,000. In about 80% of cases the presence of psoriasis precedes the onset of psoriatic arthritis [2].
Moderate to severe psoriatic arthritis - second-line
Oral

Further information

Yes

Trial or other data

Apr 21PIII SELECT – PsA 1 RCT (n=1704) found percentage of patients who had ACR20 response at week 12 was significantly higher with 15-mg or 30-mg upadacitinib than with placebo. (70.6% and 78.5% vs. 36.2%, respectively; p<0.001) but adverse events were more frequent with upadacitinib [8].
Nov 19PIII trial (NCT03104374) found both doses of upadacitinib 15 mg and 30 mg, once daily met the primary endpoint of ACR20 response at week 12 versus placebo in adult patients with active psoriatic arthritis who have responded inadequately to one or more biologic disease modifying anti-rheumatic drugs (bDMARDs) [3].
Apr 17PIII trial assessing the safety, tolerability, and efficacy of upadacitinib two doses in patients with with moderately to severely active psoriatic arthritis who have an inadequate response to biological disease modifying anti-rheumatic drugs starts (SELECT - PsA 2; NCT03104374). The primary endpoint is the proportion of patients achieving American College of Rheumatology (ACR) 20 response at 12 weeks. The trial is recruiting approximately 630 adult and elderly patients, in the US [1].
Apr 17PIII trial to compare upadacitinib with placebo and with adalimumab in patients with psoriatic arthritis who have a history of inadequate response to at least one non-biologic disease modifying anti-rheumatic drug (DMARD) starts (SELECT - PsA 1; NCT03104400). 1640 patients are being enrolled by invitation only in the US [1].

Evidence based evaluations

RinvoqActive ankylosing spondylitis (AS)

Information

Rinvoq
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

Launched
Launched
Launched
January 2021
Apr 22Company announces the FDA has approved upadacitinib for the treatment of adults with active ankylosing spondylitis [10]
Jun 21Decision on US licence application delayed due to the ongoing review into FDA safety concerns for JAK inhibitors as a class [7]
Jan 21Licence extension also approved in UK [6].
Jan 21Approved in EU [5].
Dec 20Recommended for EU approval by CHMP - the additional indication is "the treatment of active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy" [4].
Aug 20Filed in the US. An application to the EMA has also been filed earlier in the year (date not specified but presumed to be June or July) [3].

Category

Oral small molecule JAK1-selective inhibitor
Prevalence of AS 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. Male:female ratio is 3:1. Women tend to have milder or subclinical disease [1].
Active ankylosing spondylitis (AS)
Oral

Further information

Yes

Trial or other data

Aug 22PIII RCT SELECT-AXIS 2 (23 countries; n=295) found upadacitinib treatment achieved a significantly higher ASAS40 response rate vs placebo at week 14 (45% vs 23%, 95% CI 12-32, p<0.0001). The rate of adverse events was similar in both groups (48% vs 46%) [9].
Nov 21Results from the open-label extension of the SELECT-AXIS 1 (NCT03178487) study show sustained efficacy over 1 year, with ≥70% of patients receiving 15 mg once daily, or switching from placebo at week 14, achieving ASAS40 response at week 64 [9].
Oct 21PIII SELECT-AXIS 2 RCT evaluated the efficacy and safety of 15mg daily upadacitinib in pts with active ankylosing spondylitis and an inadequate response to biologic DMARD therapy. Significantly more upadacitinib -treated pts achieved SpondyloArthritis International Society (ASAS) 40 response at week 14 vs placebo (45% vs 18%; p<0.0001). Safety data were consistent with SELECT-AXIS 1 [8].
Nov 19PII/III SELECT-AXIS 1 RCT (NCT03178487; n=187) found that more patients given upadacitinib had an Assessment of SpondyloArthritis international Society 40 response by week 14 vs placebo (52% vs 26%, p=0.0003). Adverse effects were reported in 62% of patients on upadacitinib vs 55% for placebo [2].

RinvoqModerate to severe atopic dermatitis

Information

Rinvoq
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

Launched
Launched
Launched
September 2021
Jan 22Approved in the US [20]
Sep 21New 30mg Rinvoq tablet available in UK. Price £1,611.12 for 28 tabs (price for 15mg tabs x 28 is £805.56) [19].
Aug 21Approved in UK [18].
Aug 21Approved in EU [17].
Jun 21Extension to existing indication recommended for EU approval by CHMP – the new indication is “Rinvoq is indicated for the treatment of moderate to severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy [15].
Apr 21In the US, the FDA has pushed back the decision by 3 months following safety concerns for the JAK inhibitor class. A decision is now expected in Q3 2021 [14].
Oct 20Abbvie announced that it has submitted applications to the U.S. FDA and EMA seeking approval for upadacitinib for the treatment of adults (15 mg and 30 mg, once daily) and adolescents (15 mg, once daily) with moderate to severe atopic dermatitis [11].
Jan 18Upadacitinib Granted Breakthrough Therapy Designation From the FDA for Atopic Dermatitis.[3]
Sep 17After reporting positive PIIb trial results, AbbVie are preparing to start PIII trials in 2018. There is speculation that the drug may get a faster than expected approval in the US on the basis of the PIIb results, as was the case with dupilumab [1].

Category

Oral small molecule JAK1-selective inhibitor
Atopic eczema is common and the prevalence is increasing. Eczema affects 15-20% of school children and 2-10% of adults.
Moderate to severe atopic dermatitis
Oral

Further information

Yes

Trial or other data

Aug 21Results of PIII Heads Up RCT (n=692) reported in JAMA [16].
May 21Results of PIII trials Measure Up 1 and Measure Up 2 reported in The Lancet [13].
Dec 20Abbvie report positive results from PIII Heads Up study. In adults with moderate to severe atopic dermatitis, an improvement of at least 75% in EASI 75)at week 16 was achieved in 71% of patients treated with upadacitinib and 61% of those treated with dupilumab (p=0.006) [12].
Jul 20Abbvie report positive results from PIII Measure Up 2 study. An EASI 75 response at week 16 was achieved in 60% (15mg upadacitinib) and 73% (30mg) vs. 13% with placebo (p<0.001) [10].
Jun 20Abbvie report positive results from PIII NCT03569293 study. An EASI 75 response at week 16 was achieved in 70% (15mg upadacitinib) and 80% (30mg) vs. 16% with placebo (p<0.001). A validated Investigator´s Global Assessment for Atopic Dermatitis of clear or almost clear was achieved by 48%, 62% and 8%, respectively (p<0.001) [9].
Nov 19Current estimated primary completion date for PIII NCT03738397 is Sept 2020 [8].
Feb 19PIII trial to evaluate the safety and efficacy of upadacitinib compared with dupilumab in adult patients with moderate to severe atopic dermatitis who are candidates for systemic therapy has started (NCT03738397). The primary endpoint of the study is to determine the percentage of patients achieving a 75% reduction in Eczema Area and Severity Index (EASI 75) from baseline, at week 16. The randomised, double-blind trial intends to enrol approximately 650 adult patients in the US and may expand to other locations [7].
Nov 18PIII trial to assess the safety of upadacitinib combined with topical corticosteroids in adolescent and adult participants with moderate to severe atopic dermatitis who are candidates for systemic therapy (NCT03661138) has started; the double-blind, randomised trial is enrolling approximately 264 patients in Japan [7]. 28/05/2019 14:16:16
Aug 18Two PIII trials have started: AD Up trial (NCT03568318) and Measure Up 1 trial (NCT03569293), both aim to assess the efficacy and safety of upadacitinib in combination with topical corticosteroids for the treatment of adolescents and adults with moderate-to-severe atopic dermatitis who are candidates for systemic therapy. The estimated primary completion date for both is December 2019 [5,6].
Jul 18PIII trial (NCT03607422) to assess the efficacy and safety of upadacitinib for the treatment of adolescents (over 12 years old) and adults with moderate-to-severe atopic dermatitis who are candidates for systemic therapy has started. The estimated primary completion date is January 2020 [5,6]
Feb 18Abbvie announce new data from PIIb study NCT02925117. Across all doses (30/15/7.5 mg once-daily), exploratory results showed significant reduction in pruritus at week 1 (39, 56, 59% decrease vs. 9% placebo, p<0.001) and improvement in the extent and severity of skin lesions at week 2 (29, 46 and 58%, vs. -2%; all p<0.001) [4]

Evidence based evaluations

RinvoqUlcerative colitis (UC)

Information

Rinvoq
Licence extension / variation and new formulation
AbbVie
AbbVie

Development and Regulatory status

Approved (Licensed)
Approved (Licensed)
Launched
Jul 22MHRA approves a new indication for Rinvoq 15mg and 30mg prolonged-release tablets for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent, plus approves a new 45mg prolonged-release tablet for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, atopic dermatitis, and ulcerative colitis [14].
Jul 22EMA approves an extension application to add a new strength (45 mg) of the prolonged-release tablets, grouped with a type II variation for the existing 15mg and 30mg strengths to include the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent [13].
May 22EU positive opinion granted recommending a licence change to include use “for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent” [11].
Mar 22Approved in US [10].
Sep 21Filed in EU and US for treatment of adults with moderately to severely active ulcerative colitis, who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent [9].

Category

Oral small molecule JAK1-selective inhibitor
UC has an incidence in the UK of approximately 10 per 100,000 people annually and a prevalence of approximately 240 per 100,000 [3].
Ulcerative colitis (UC)
Oral

Further information

Yes

Trial or other data

May 22Results of PIII trials U-ACHIEVE and U-ACCOMPLISH reported in The Lancet [12].
Jun 21Further results from the PIII U-ACHIEVE study announced by AbbVie. In this part of the study investigating upadacitinib as maintenance treatment, adults with moderate to severe UC who achieved a clinical response following an 8-week period of once-daily upadacitinib 45 mg induction treatment (n=451) were re-randomised to receive upadacitinib 15 mg, upadacitinib 30 mg or placebo for an additional 52 weeks. Significantly more upadacitinib-treated patients achieved clinical remission at week 52 vs placebo (15 mg: 42% and 30 mg: 52% vs placebo: 12%; p<0.001) and all secondary endpoints were met, including the achievement of endoscopic improvement, HEMI and corticosteroid-free clinical remission. Safety results were consistent with the previous PIII induction studies and the known safety profile of upadacitinib, with no new safety risks observed. This trial is no longer recruiting. A long-term global safety and efficacy PIII trial (NCT03006068) is enrolling with primary completion due Aug 2024 [7,8].
Feb 21PIII U-ACCOMPLISH study meets primary endpoint of clinical remission (per Adapted Mayo Score); 33% of patients receiving upadacitinib (45mg once daily) achieved clinical remission at week 8 vs 4 % receiving placebo (p<0.001) [6].
Dec 20Positive results from PIIb/III U-ACHIEVE of upadacitinib for induction and maintenance therapy of moderate to severe UC. At week 8, 26% of pts receiving upadacitinib achieved clinical remission (primary endpoint) vs. 5% in the placebo group. Endoscopic improvement at week 8 was seen in 36% of pts receiving upadacitinib vs. 7% of placebo pts. Histologic-endoscopic mucosal improvement at week 8 was seen in 30% of upadacitinib pts vs. 7% with placebo and 73% achieved clinical response per the Adapted Mayo Score vs. 27% with placebo group. Clinical response was reported by 60% upadacitinib at week 2 vs. 27% with placebo. However, it is worth noting that upadacitinib has a JAK class warning label regarding serious infections, malignancy and thrombosis. [5]
Dec 19The PIII U-Accomplish (NCT03653026) and U-ACHIEVE (NCT02819635) trials are still recruiting, with estimated primary completion dates of Feb 2021 and Apr 2021, respectively [4].
Nov 18U-ACHIEVE study = NCT02819635. Collection of primary outcome data due to complete Apr 21. Second study also underway (NCT03653026) [2].
Oct 18Results from P2b/III trial U-ACHIEVE evaluating upadacitinib for induction and maintenance therapy in adults with moderate to severe ulcerative colitis found more patients had clinical remission on upadacitinib than placebo. Using Adapted Mayo Score, 14/14/20 percent of patients on 15/30/45 mg once daily had remission compared to placebo (0 percent) at week 8. Secondary endpoints were also met [1].

Evidence based evaluations

RinvoqAxial spondyloarthritis

Information

Rinvoq
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

Launched
Launched
Launched
August 2022
Oct 22FDA approves use of upadacitinib in adults with active non-radiographic axial spondyloarthritis (nr-axSpA). The approval covers patients with objective signs of inflammation who have either failed on or were not suitable for tumor necrosis factor (TNF) blockers [11].
Aug 22MHRA approves new indication for Rinvoq 15mg and 30mg tablets, for treatment of active non-radiographic axial spondyloarthritis in adult patients with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs) [10].
Jul 22New indication approved in EU [8].
Jun 22Recommended for EU approval by CHMP – the extension to the existing indication is “for the treatment of active non-radiographic axial spondyloarthritis in adult patients with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs)” [7].
Jan 22Filed in EU and US for the treatment of adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation who have responded inadequately to NSAIDs [7].

Category

Oral small molecule JAK1-selective inhibitor
Spondyloarthritis (SpA) is a constellation of chronic inflammatory conditions that includes ankylosing spondylitis (AS), reactive arthritis, enteropathic arthritis, and psoriatic arthritis, among others. Collectively, prevalence of SpA varies between 0.5 % and 2 %, making it approximately as common as rheumatoid arthritis. Patients with SpA can be categorized as having axial SpA, in which the spine is predominantly affected, or peripheral [1].
Axial spondyloarthritis
Oral

Further information

Yes

Trial or other data

Oct 21Study 1 of PIII 3 SELECT-AXIS 2 trial meets primary endpoint of ASAS40 at week 14 vs. placebo (45% vs 18%) in patients with ankylosing spondylitis and inadequate response to bDMARD therapy [4].
Oct 21Study 2 of PIII 3 SELECT-AXIS 2 trial (n=313) meets primary endpoint. Assessment in SpondyloArthritis International Society (ASAS) 40 response at week 14 is 45% with upadacitinib 15mg OD vs. 23% with placebo. Safety data are consistent with SELECT-AXIS 1 and the known safety profile of upadacitinib [5].
Feb 21Estimated primary completion date for PIII NCT04169373 is now Feb 2023 [3].
Nov 19PIII study starts (NCT04169373). The protocol includes 2 standalone studies with randomisation, data collection, analysis and reporting conducted independently. The main objectives of this protocol are: To evaluate the efficacy of upadacitinib compared with placebo on reduction of signs and symptoms in adult participants with active axial spondyloarthritis (axSpA) including biologic disease-modifying antirheumatic drug inadequate responders (bDMARD-IR) ankylosing spondylitis (AS) (Study 1) and non-radiographic axial spondyloarthritis (nr-axSpA) (Study 2). Also to assess the safety and tolerability of upadacitinib in adult participants with active axSpA including bDMARD-IR AS (Study 1) and with nr-axSpA (Study 2). 690 adults will be recruited in the UK, Eastern Europe, Western Europe, North America, South America, Asia, Australia and Oceania. Primary outcome in Study 1: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) 40 Response at week 14. In Study 2, it is: Percentage of Participants Achieving Assessment of SpondyloArthritis International Society (ASAS) 40 Response. Collection of primary outcome data is due to complete Jun 22 [2].

Evidence based evaluations

RinvoqCrohn's disease

Information

Rinvoq
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
Jul 22Filings submitted to FDA and EMA for upadacitinib 45mg (induction dose) and 15mg and 30mg (maintenance dose) for the treatment of adult patients with moderately to severely active Crohn´s disease [7].
May 22Filings to the FDA planned for later this year. If successful, Rinvoq would become the first JAK inhibitor endorsed for use against Crohn ’s [6].

Category

Oral small molecule JAK1-selective inhibitor
Prevalence in the UK is about 145 per 100.000 population [1].
Crohn's disease
Oral

Further information

Yes

Trial or other data

May 22AbbVie announces upadacitinib has been shown to be effective as a maintenance therapy in the 52-week U-ENDURE study. For the year long study, patients who responded well to the 45-mg dose in the induction phase of those earlier trials were re-randomised to receive a 30-mg or 15-mg dose of the drug or placebo. Of those who took the higher dose, 48% achieved clinical remission , and 37% of patients on the lower drug dose vs. 15% for the placebo group. Those dosed with Rinvoq 30 mg and 15 mg showed more endoscopic response­ at 40% and 28%, respectively, versus 7% on placebo. They also showed more endoscopic remission at 29% and 19% for the high dose and low dose, respectively, versus 5% on placebo [6].
Feb 22In PIII U-EXCEL study (NCT03345849) patients with inadequate response/intolerance to at least one conventional and/or biological therapy, a12-week induction with upadacitinib achieved both primary endpoints of clinical remission (49% v 29% placebo; p<0.0001) and endoscopic response (46% v 13%; p<0.0001) [5].
Dec 21PIII U_EXCEED trial (NCT03345836) meets primary and secondary endpoints. In patients who had inadequate response or were intolerant to biologic therapy, a 12-week induction regimen of upadacitinib achieved both primary endpoints of clinical remission (39% vs 21% placebo; p<0.0001) and endoscopic response (35% vs 4%; p<0.0001) at week 12 [5].
Jan 21 PIII trials (NCT03345836 and NCT03345849) are still recruiting, with estimated primary completion dates of Jun 2021 and Sept 2021, respectively. The PIII maintenance and long-term extension study (NCT03345823) is recruiting by invitation with an estimated primary completion date of Aug 2027 [4].
Dec 19Two PIII trials (NCT03345836 and NCT03345849) are still recruiting, with estimated primary completion dates of Jun 2021 and Sept 2021, respectively. A PIII maintenance and long-term extension study (NCT03345823) is ongoing with an estimated primary completion date of Jan 2022 [3].
Feb 19PIII trial (NCT03345849) is also recruiting. Collection of primary outcome data expected to complete Dec 19 [2].
Feb 19PIII trial (NCT03345836) is recruiting. Collection of primary outcome data expected to complete Jan 20 [2].
Mar 18PIII maintenance and long-term extension study to assess the safety and efficacy of maintenance and long-term treatment administration of upadacitinib, in patients with Crohn´s disease starts (NCT03345823). The randomised, double blind, placebo-controlled trial is designed to enrol approximately 738 patients. Co-primary outcome is proportion of participants with clinical remission at week 52 & proportion of participants with endoscopic response; collection of these data is due to complete Jan 19 [2].
Nov 17Another PIII trial of similar trial design in approximately 300 patients in the the US starts (NCT03345849) [2].
Nov 17PIII trial to evaluate the efficacy and safety of upadacitinib compared to placebo as induction therapy in subjects with moderately and severely active Crohn´s disease who have inadequately responded to or are intolerant to biologic therapy starts (NCT03345836). 855 patients will be recruited from countries around the world including the US, EU & UK [2].

Evidence based evaluations

Rinvoq Giant cell (temporal) arteritis

Information

Rinvoq
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

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

Category

Oral small molecule JAK1-selective inhibitor
UK prevalence has been estimated as 0.25% in the population aged at least 55 years as of 2013 using data from a single large practice in Norfolk [1]. It is rare in those under 50 and rates increase with age, peaking around age 80; in Northern Europe, it is more common in females (ratio about 2.5:1). It is considered to be more common in Caucasian populations than non-Caucasian, and incidence is highest in Scandinavians and in populations with high Scandinavian ancestry [2].
Giant cell (temporal) arteritis
Oral