To create an alert for the Global Brand Director of Entyvio at Takeda to inform the latest development, highlighting the relevance of the news and its implications for Takeda

1. AbbVie presents positive topline results from the Phase-3 maintenance study (FORTIFY) showing Skyrizi SC
achieves co-primary endpoints at week-52 in patients with moderate-severe Crohn’s disease
Sources: 1. AbbVie Press Release 2. PRNewswire 3. NCT03105102 4. NCT03105128 5. NCT03104413
Skyrizi® (risankizumab): IL-23 inhibitor developed by AbbVie in partnership with BI
[02-Jun-2021] Phase-3 maintenance results show patients with Crohn's disease receiving risankizumab (Skyrizi®) achieved
endoscopic response and clinical remission at one year1,2
Endpoints Skyrizi SC (180mg)
(N=157)
Skyrizi SC (360mg)
(N=141)
Skyrizi IV (N= 164)
(Control group)
Endoscopic Response (ER)
(Primary endpoint - US Plan)
47%
(P<0.001)
47%
(P<0.001)
22%
Clinical Remission (CDAI)
(Primary endpoint - US Plan)
55%
(P<0.001)
52%
(P<0.001)
41%
Clinical Remission (SF/AP)
(Primary endpoint – OUS Plan)
46%
(P>0.005)
52%
(P<0.001)
40%
Endoscopic Remission (ER)
(Secondary endpoint - OUS)
30%
(P<0.001)
39%
(P<0.001)
13%
Deep Remission
(Secondary endpoint - OUS)
25%
(P<0.001)
29%
(P<0.001)
10%
FORTIFY Efficacy Results @ WK-52
BI – Boehringer Ingelheim, SC – Subcutaneous, IV – Intravenous, WK – Week, CDAI – Crohn’s disease activity index, SF/AP – Stool frequency/Abdominal pain, OUS – Outside US, RCT – Randomized controlled trial
Skyrizi SC (360 mg, @ every WK-8)
Met co-primary endpoints in both the US /
Outside the US (OUS) analysis plan
Nearly half of patients achieved both the
primary endpoints
FORTIFY Safety Results @ WK-52: No new safety risks were observed – nearly consistent with the known safety profile of risankizumab
 Rates of serious adverse events were 12.3% and 13.4% in subjects treated with Skyrizi 180 or 360mg respectively, vs. 12.5% in control group
Skyrizi SC (180 mg, @ every WK-8)
Met co-primary endpoints in the U.S. analysis
plan, but not in the OUS analysis plan
The FORTIFY study [NCT03105102]3 evaluated two doses: 180mg and 360mg of subcutaneous (SC) Skyrizi in moderate-severe Crohn’s patients
 Multi-centre, randomized, double-blind, control group, 52-week Phase 3 open-label extension study (US, EU, UK, Japan, Canada, China)
 Two analysis plans for clinical remission: Crohn's disease activity index (CDAI) for the US analysis plan, and stool frequency and abdominal
pain (SA/AP) the outside of the US analysis plan — due to regulatory requirements in the different regions

2. Sources: 1. AbbVie Press Release 2. Skyrizi - Advance/Motivate 3. Skyrizi Approval 4. Entyvio SC – SmPC 5. Entyvio Website
Skyrizi SC vs. Entyvio SC: As Crohn’s Disease Maintenance Therapy
SC – Subcutaneous, WK – Week, OUS – Outside the US
Skyrizi SC shows better compliance rate as compared to Entyvio SC
Skyrizi SC (180/360mg) at every 8-weeks [once in 2-months]1 Entyvio SC (108mg) at every 2-weeks [twice in a month]4
COMPLIANCE
Skyrizi SC reported more significant clinical endpoints – with quicker onset of action as compared to Entyvio SC
Clinically significant endpoints evaluated such as Endoscopic
Response and Clinical Remission [both are primary endpoints]1
Skyrizi SC (360mg) achieved both co-primary and secondary
endpoints1
Skyrizi has faster onset of action [starts to work within 4-weeks]2
Clinical Remission was only evaluated as primary endpoint5
Secondary endpoints (Clinical Response) was not statistically
significant [52% Entyvio vs. 44.8% placebo]5
At week-6 considered to reflect early onset of action5
CLINICAL
OUTCOMES
Skyrizi SC has higher chance to get launched in the US market – before Entyvio SC
Expected approval in Q2-20223: Skyrizi SC (360 mg, @WK-8)
met co-primary endpoints in both the US / OUS analysis plan
Approved in EU, Canada, Australia; However Entyvio SC has
been rejected by the US FDA
COMMERCIAL
DATA
Skyrizi SC and Entyvio SC – both have comparable safety profile
Safety profile of both tested doses of Skyrizi SC was in-line with
prior data [no new safety risks were reported]1
Favorable safety profile with 'No-box warning‘5
SAFETY
PROFILE
Skyrizi SC Entyvio SC
Entyvio will face significant competition from AbbVie’s Skyrizi which has higher compliance, favorable
clinical outcomes with faster-onset of action, and comparable safety profile
Lead/ Superiority
Negative/ Inferiority

3. Sources: 1. Seeking Alpha
Skyrizi SC vs. Entyvio SC: Recommendations
AbbVie’s Skyrizi has competitive edge over Entyvio based on new late-phase 3 clinical data:
1.
Better compliance with Skyrizi as subcutaneous formulation is taken 'once in 2-months' whereas
Entyvio SC is prescribed 'twice in a month'
2.
Might have higher acceptance within HCPs as more significant clinical endpoints were
evaluated in Skyrizi trial (such as endoscopic response, deep remission)
3.
Skyrizi has faster onset-of-action: Quicker onset-of-action is a leading parameter for HCPs
as one-third patients were found to be non-responder to biologics
4. High probability for the US launch before Entyvio; Also AbbVie’s strong relationship
with payers to secure positive formulary positioning
“AbbVie's replacements for Humira (Skyrizi and Rinvoq) are rapidly growing and will eventually make up for the
drop in sales as generics begin to pressure Humira” [Seeking Alpha, Jun-04, 2021]1

4. 2.