dm+d

37138511000001105

New Medicines

SkyriziModerate-to-severe chronic plaque psoriasis in adults

Information

Skyrizi
New molecular entity
AbbVie
AbbVie

Development and Regulatory status

Launched
Launched
Launched
May 2019
Jun 21Skyrizi 150mg pre-filled pen and syringe approved and available in the UK. Price £3,326.09 per pen/syringe [24,25].
May 19Approved in EU [17].
May 19Available through AbbVie (direct orders from hospital pharmacy) or via the homecare providers : Alcura, Healthcare at Home or Healthnet [19].
May 19Launched in the UK. £3,326.09 per pack. Packsize = 2 x 75mg pre-filled syringe [18] [19].
Apr 19In the US, Skyrizi will be priced at $88,500 for the first year and $59,000 per year for maintenance doses [16].
Mar 19A new market research report identifies risankizumab as one of seven new drugs it believes will hit sales of $1 billion or more, the so-called “blockbuster” mark, by 2023 [14].
Feb 19Recommended for EU approval by CHMP - the full indication is "for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy”. It is proposed that the drug be prescribed by physicians experienced in the treatment of psoriasis [13].
May 18Filed in the EU for treatment of moderate-to-severe plaque psoriasis. The application is supported by data from four pivotal PIII studies: ultIMMA-1, ultIMMa-2, IMMhance and IMMvent [10].
Apr 18Approved in US [15].
Apr 18Filed in the US [9].
May 17Global launches predicted in 2019 [5].
Mar 16AbbVie pays over $595 million to partner with Boehringer Ingelheim on BI-655066. AbbVie will share in late-stage development while gaining sole marketing rights [3].

Category

A humanised IgG1 monoclonal antibody that binds to and neutralises the p19 subunit of interleukin-23.
The prevalence of psoriasis is around 1.3-2.2% in the UK.
Moderate-to-severe chronic plaque psoriasis in adults
Subcutaneous injection

Further information

Yes

Trial or other data

Jan 20Risankizumab met both primary and all ranked secondary endpoints in PIII trial (NCT03478787) vs. secukinumab in plaque psoriasis. The trial was a head-to-head, multicentre, open-label non-inferiority study in 327 adults with moderate to severe plaque psoriasis. At week 16, 74% of pts on risankizumab acheived PASI 90 vs. 66% on secukinumab, demonstrating non-inferiority. Of pts treated with risankizumab (75mg at week 0, 4 and then every 12 weeks), 87% achieved PASI 90 vs. 57% treated with secukinumab (150mg at weeks 0,1, 2, 3 and 4, then every 4 weeks after) at 52 weeks (p<0.001). Adverse events were comnparable and no new safety signals were observed [22,23].
Jul 19PIII IMMvent RCT (n=605) is published; it found risankizumab (RI) superior to adalimumab (AD) for PASI90 response at week 16 (72 vs 47%, p<0.0001). At 16 weeks AD intermediate responders were re-randomised to RI or AD; by week 44 PASI90 was achieved in 66% switched vs 21% continuing on AD (p<0.0001) [21].
Jun 19New 2-year data from the ongoing PIII IMMhance study reported at the World Congress of Dermatology showed 73% and 72% of patients treated with continuous risankizumab experienced complete skin clearance (defined as sPGA 0 and PASI 100, respectively) at week 94, among patients who achieved sPGA 0/1 at week 28. No new safety findings observed at 2 years (104 weeks) [20].
Sep 18Pooled analyses from ultIMMa-1 and ultIMMa-2 studies showed significantly more pts treated with risankizumab were symptom-free vs. placebo and ustekinumab. At week 16, 30% of pts receiving risankizumab had a PSS score of 0 vs. 15% and 1% receiving ustekinumab and placebo, respectively (p<0.001). At 1 year, 56% of risankizumab-treated pts reported being symptom free (PSS=0) vs. 30% of pts receiving ustekinumab (p<0.001) [12].
Aug 18Results of UltIMMa-1 and UltIMMa-2 published in The Lancet [11].
Feb 18Abbvie present data from PIII UltIMMa-1 trial (NCT02684370) and UltIMMa-2 trial (NCT02684357) at conference. Results at weeks 16 and 52 demonstrate significantly higher rates of clear skin (as measured by static Physician Global Assessment), both ranked secondary endpoints, in patients treated with risankizumab, compared to ustekinumab or placebo (P<0.001) [8].
Nov 17IMMhance (NCT02672852) study (n=500) meets all primary endpoints. At week 16, 73% of patients receiving risankizumab achieved PASI90 vs 2% of patients receiving placebo. Additionally, 47% of patients on risankizumab achieved PASI100 vs 7% on placebo (p<0.001 for both comparisons vs placebo) [7].
Oct 17Three phase III trials found that risankizumab was better than either ustekinumab or adalimumab in moderate-severe plaque psoriasis. In ultIMMa-1 (NCT02684370) and ultIMMa-2 (NCT02684357), patients were given risankizumab (150 mg) or ustekinumab 45 mg or 90 mg at week 0, 4, 16, 28, 40. After 16 weeks, PASI 90 was 75% in the risankizumab group compared with 42% in the ustekinumab group and 5% in the placebo group; 75%, 48% and 2% respectively in the ultiMMa-2 trial. The PIII IMMvent study (NCT02694523) compared risankizumab with adalimumab. Patients were randomized to either risankizumab (150 mg), given as a subcutaneous injection at baseline, 4 weeks later and every 12 weeks thereafter or adalimumab, given as a subcutaneous injection, with an initial dose of 80 mg followed by 40 mg every other week starting one week after the initial dose. PASI 90 at 16 weeks was 72% (n=301) with risankizumab and 47% in the adalimumab group (n=304) [6 ].
Apr 17PIII UltIMMa-1 trial (NCT02684370) and UltIMMa-2 trial (NCT02684357) have completed recruitment. Collection of primary outcome data was due to complete Dec 16 [4].
Feb 17Open-label PIII LIMMITLESS extension trial to assess the long term safety and efficacy of 150mg risankizumab in the treatment of moderate to severe chronic plaque psoriasis starts. The trial will enrol approximately 1900 subjects aged 18 to 99 years in the US and Canada. Patients from the previous PII/III studies will be rolled over in this study [5].
Feb 16Boehringer Ingelheim plans to conduct the PIII UltIMMa-2 trial to investigate safety and efficacy of risankizumab to support registration for treatment of patients with moderate to severe chronic plaque psoriasis (NCT02684357). The randomised, double-blind trial will enrol approximately 500 participants in Belgium, Canada, the Netherlands, Spain, the US, France, Germany, Italy, Mexico, Portugal, Austria and Poland [2].
Feb 16Boehringer Ingelheim plans to conduct the PIII UltIMMa-1 trial to investigate safety and efficacy of risankizumab to support registration for thtreatment of patients with moderate to severe chronic plaque psoriasis (NCT02684370). The randomised, double-blind trial will enrol approximately 500 participants in the US, Canada, Czech Republic, France, Germany, Japan, South Korea and Australia [2].
Feb 16Boehringer Ingelheim initiates the PIII IMMhance trial to evaluate safety and efficacy of risankizumab in patients with moderate to severe plaque psoriasis (NCT02672852). The study will assess maintenance of response following treatment withdrawal, as well as response to re-treatment for patients who relapse. The randomised, double-blind trial has initiated enrolment of approximately 500 patients in the US, Canada, and is expected to expand in Belgium, France, South Korea and Germany [2].
Feb 16NCT02694523 = IMMvent trial [2].
Feb 16PIII study (NCT02694523) to assess safety and efficacy of BI 655066 compared to adalimumab to support registration for treatment of moderate to severe chronic plaque psoriasis in adults begins. 600 adults will be recruited from sites in Finland, France, Germany, Great Britain, Italy, Mexico, Poland, Portugal, Taiwan, US, Canada, Czech Republic, & Sweden. Co-primary outcomes are Achievement of >=90% reduction from baseline Psoriasis Area and Severity Index (PASI) score (PASI 90) at Week 16 and Achievement of a static Physician Global Assessment (sPGA) score of clear or almost clear at Week 16. Collection of these data are expected to complete Mar 17 [1].

Evidence based evaluations

SkyriziPsoriatic arthritis

Information

Skyrizi
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

Launched
Launched
Launched
Jan 22Licence extension approved in the US. US approval is to treat moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, as well as to treat active psoriatic arthritis in adults. The approved dose is 150 mg (one 150 mg pre-filled pen or pre-filled syringe) administered by SC injection at weeks 0 and 4, and every 12 weeks thereafter [13].
Nov 21Licence extension approved in UK. Skyrizi, alone or in combination with methotrexate (MTX), is indicated for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to one or more disease-modifying antirheumatic drugs (DMARDs) [12].
Oct 21Recommended for EU approval by CHMP – the additional indication is “for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to one or more disease-modifying antirheumatic drugs (DMARDs)” [10].
Apr 21AbbVie submits applications to EMA and US FDA for treatment of adults with active psoriatic arthritis [8].
Mar 19PIII studies start [5,6].
Jan 18Listed as PII in AbbVie pipeline [4].

Category

Humanised IgG monoclonal antibody that selectively blocks IL-23
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 [1].
Psoriatic arthritis
active
Subcutaneous

Further information

Yes

Trial or other data

Sep 21 Abbvie report long-term open-label extension data from KEEPsAKE-1 and KEEPsAKE-2; at 52 weeks, an ACR20 response was achieved by 70% and 58% of patients initially treated with risankizumab. ACR50 and ACR70 responses were achieved by 43% and 32%, and by 26% and 17%, respectively [8].
Jan 21Abbive report positive data from two PIII trials In KEEPsAKE-1 and KEEPsAKE-2, more patients treated with risankizumab 150 mg achieved the primary endpoint of ACR20 response at week 24 vs placebo; 57 and 51% of treated patients vs 34 and 27% placebo respectively; p<0.001) [7].
Mar 19A PIII trial (NCT03675308) evaluating risankizumab vs. placebo in patients with active psoriatic arthritis who have a history of inadequate response to, or intolerance to, at least one DMARD starts; the estimated primary completion date is January 2021 [5,6].
Mar 19The PIII IMMpact2 trial (NCT03671148), evaluating the safety and efficacy of risankizumab in the patients with moderately to severely active psoriatic arthritis, has started; the estimated primary completion date is January 2021 [5,6].
Nov 16AbbVie initiates an extension PII trial to evaluate the efficacy, safety and tolerability of risankizumab SC injection in psoriatic arthritis patients who have completed all doses of study drug and the Week 24 visit in Study 1311.5 (M16-244; EudraCT2016-003113-94). The open-label trial is recruiting 180 patients in Finland, Belgium and Spain, and will extend to the US, Canada, Japan, Taiwan and other EU countries [3].
Apr 16Boehringer Ingelheim initiates a PII trial to evaluate efficacy and safety of different subcutaneous doses of risankizumab in adult patients with psoriatic arthritis, in order to select doses for further clinical trials (NCT02719171; M16-002). The trial is enrolling approximately 180 patients in the US, Canada, Finland, France, Germany, Japan, the Netherlands, Poland, Spain, Taiwan, the Czech Republic and Belgium [2].

Evidence based evaluations

SkyriziModerate-to-severe Crohn's disease

Information

Skyrizi
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Launched
Yes
Jun 22FDA approves risankizumab to treat adults with moderate to severely active Crohn ’s disease [12].
Apr 22MHRA grants Early Access to Medicines Scheme (EAMS) status to AbbVie for risankizumab for treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to, lost response to, or were intolerant or contraindicated to tumour necrosis factor-alpha (TNFα) antagonist therapies, vedolizumab and ustekinumab and for the treatment of adolescent patients aged 16 to 17 years with moderately to severely active Crohn’s disease who have had an inadequate response to, lost response to, or were intolerant or contraindicated to TNFα antagonist therapies [9].
Nov 21Filed in EU [9].
Sep 21AbbVie announces it has submitted an application to FDA for risankizumab-rzaa for treatment of moderate to severe Crohn´s disease in patients 16 years and over. [8]
Nov 16Granted orphan drug designation for the treatment of Crohn´s disease in paediatric patients in the US [1].

Category

Humanised IgG monoclonal antibody that selectively blocks IL-23
There are currently at least 115,000 people in the UK with Crohns disease [3].
Moderate-to-severe Crohn's disease
Intravenous infusion and
Subcutaneous injection

Further information

Yes

Trial or other data

May 22PIII FORTIFY RCT (NCT03105102) at 52 weeks reported greater clinical remission and endoscopic response rates with subcutaneous risankizumab 360mg vs placebo (n=542; 52% vs 41%) and with subcutaneous risankizumab 180 mg vs withdrawal (55% vs 47%) [11].
May 22PIII ADVANCE and MOTIVATE RCTs report improved clinical remission rates with intravenous risankizumab in patients with moderately to severely active Crohn's disease (ADVANCE; n=931; 45% with 600 mg; 42% with 1200 mg vs 25% with placebo: MOTIVATE; n=618; 42%, 40% vs 20%, respectively) [10].
May 21Data from PIII ADVANCE and MOTIVATE trials presented at Digestive Disease Week® (DDW) Virtual Conference 2021. Risankizumab met the co-primary endpoints of clinical remission and endoscopic response at week 12 vs. placebo.[7]
Jan 21Abbvie report positive topline data from PIII trials. In ADVANCE (patients with inadequate response or intolerant to conventional and/or biologic therapy), NCT03105128 and MOTIVATE (inadequate response or intolerant to biologic therapy), NCT03104413, both 600mg and 1200mg doses met primary endpoints of clinical remission and endoscopic response at week 12 [6].
Dec 19The PIII induction trials (NCT03105128 and NCT03104413) are still recruiting, with an estimated primary completion date of Mar 2021. The PIII open-label extension (maintenance) study (NCT03105102) is also ongoing with an estimated primary completion date of Oct 2025 [5].
Apr 18PIII open-label extension study (NCT03105102) is also recruiting [4].
Apr 18PIII induction trials (NCT03105128 and NCT03104413) are recruiting globally, including in the US & EU (plus UK) [4].
Apr 17Two multicentre, randomised, double-blind PIII induction trials (NCT03105128 and NCT03104413) and a multicentre, randomised, double-blind, 52-Week maintenance trial and open-label extension study (NCT03105102) are planned to commence this year to investigate the efficacy and safety of risankizumab IV and SC vs. placebo in patients aged 16-80 years with moderate to severe Crohn´s disease. Primary outcome measures are percentage of participants with clinical remission per average daily stool frequency (SF) and average daily abdominal pain (AP) score at Week 12, and percentage of participants with endoscopic response at Week 12. NCT03105128 (n=940 planned) has an estimated primary completion date of Oct 19; NCT03104413 (n=579 planned) has an estimated primary completion date of Mar 19; NCT03105102 (n=912 planned) has an estimated primary completion date of Apr 20 [2].

Evidence based evaluations

SkyriziModerate-to-severe ulcerative colitis (UC) in adults who have had an inadequate response to or were intolerant to aminosalicylate, corticosteroid, or immunomodulator, or biologic therapy

Information

Skyrizi
Licence extension / variation
AbbVie
AbbVie

Development and Regulatory status

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

Category

Humanised IgG monoclonal antibody that selectively blocks IL-23
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 [1].
Moderate-to-severe ulcerative colitis (UC) in adults who have had an inadequate response to or were intolerant to aminosalicylate, corticosteroid, or immunomodulator, or biologic therapy
Subcutaneous injection

Trial or other data

Dec 19The PII/III study (NCT03398148) to identify the appropriate induction dose of risankizumab is ongoing with an estimated primary completion date of Sept 2020.The PIII trial (NCT03398135) in subjects who responded to induction treatment is also recruiting, with an estimated primary completion date of Dec 2022 [4].