Crohn's disease (CD) new drug! EU approves Skyrizi: first specific IL-23 inhibitor for the treatment of CD!

Nov.
22, 2022 /Biovalley BIOON/ -- AbbVie has announced that the European Commission (EC) has approved a new indication for the new anti-inflammatory drug IL-23 inhibitor Skyrizi (risankizumab, 150mg): Skyrizi 600mg intravenous (IV) induction and 360mg subcutaneous (SC) maintenance regimen for the treatment of inadequate response to conventional or biological therapy, Adults with moderately to severely active Crohn's disease (CD) who are unresponsive or intolerant
.

It is worth mentioning that Skyrizi is the first specific IL-23 inhibitor
approved by the European Union and the United States for the treatment of CD.
In the US, Skyrizi was approved in June 2022 for the treatment of adults with
moderately to severely active CD.
In two induction trials and one maintenance trial, Skyrizi as induction and maintenance therapy showed significant improvements
in endoscopic response and clinical remission compared with placebo.

Up to now, Skyrizi has been approved for 3 indications in the United States and the European Union: (1) for the treatment of adult patients with moderate to severe plaque psoriasis (PsO); (2) for the treatment of adult patients with active psoriatic arthritis (PsA); (3) For the treatment of adult patients
with moderately to severely active Crohn's disease (CD).

Skyrizi's mechanism of action (Image: AbbVie abbviepro.
com)

The EU approval is based on the results of
a global Phase 3 clinical program.
This project includes 3 pivotal Phase 3 clinical studies (ADVANCE induction study [NCT03105128], MOTIVATE induction study [NCT03104413], FORTIFY maintenance study [NCT03105102]).

The three pivotal Phase 3 studies were all multicenter, randomised, double-blind, placebo-controlled studies evaluating the efficacy, safety, and tolerability
of Skyrizi.

ADVANCE studies were conducted in patients who had underresponded or were intolerant to conventional therapy (non-bio-IR) and/or to biological therapies (bio-IR); The MOTIVATE study was conducted
in patients with inadequate response to or intolerance to biological therapy (bio-NR).
The FORTIFY maintenance study was conducted
in patients who responded to induction therapy with Skyrizi IV.

All three studies met the common primary endpoint (clinical response and endoscopic response) and secondary endpoints (including: mucosal healing and endoscopic remission).

Detailed efficacy data are as follows:

1.
Clinical remission and endoscopic response:

- In the Phase 3 ADVANCE and MOTIVE induction studies, the proportion of patients who received 600 mg of Skyrizi IV induction therapy at week 12 achieved a significant increase in the proportion of patients who met the common primary endpoint (clinical response and endoscopic response) at week 12 compared with placebo: (1) clinical response (ADVANCE study: 43% vs 22%; MOTIVE study: 35% vs 19%); (2) endoscopic response (ADVANCE study: 40% vs 12%; MOTIVE STUDY: 29% VS 11%)
.

- In the Phase 3 FORTIFY maintenance study, the proportion of patients receiving Skyrizi 360mg SC maintenance therapy had a significant increase in the proportion of patients who met the common primary endpoint (clinical response and endoscopic response) at one year (52 weeks) compared with those who discontinued Skyrizi (placebo): (1) clinical response (52 versus 40%); (2) endoscopic response (47% vs 22%)
.

2.
Mucosal healing and endoscopic relief

- In the Phase 3 ADVANCE and MOTIVE induction studies, the proportion of patients who received 600 mg of Skyrizi IV induction therapy achieved mucosal healing and endoscopic remission at week 12 compared with placebo: (1) mucosal healing (ADVANCE study: 21% vs 8%; MOTIVE STUDY: 14% vs 4%); (2) endoscopic remission (ADVANCE study: 24% vs 9%; MOTIVE study: 19% vs 4%)
.

- In the Phase 3 FORTIFY maintenance study, the proportion of patients receiving Skyrizi 360mg SC maintenance therapy achieved mucosal healing and endoscopic remission at one year (52 weeks) compared with those who discontinued Skyrizi (placebo): (1) mucosal healing (31 versus 10%); (2) endoscopic remission (39% vs 13%)
.

In the three studies, the safety profile of Skyrizi was consistent with the known safety profile of the drug, and no new safety risks
were observed.

Crohn's disease (CD) is a chronic systemic disease characterized by inflammation within the gastrointestinal tract (or digestive tract), causing persistent diarrhea and abdominal pain that requires emergency medical care
.
The disease is progressive, meaning it worsens
over time.
Because the signs and symptoms of CD are unpredictable, it places a huge burden
on the patient not only physically, but also emotionally and financially.

Skyrizi's active pharmaceutical ingredient is risankizumab, a monoclonal antibody drug that selectively blocks interleukin-23 (IL-23), a cytokine, a cytokine thought to play a key role
in many chronic immune diseases by specifically targeting the IL-23p19 subunit 。 Originally developed by German pharmaceutical company Boehringer Ingelheim (BI), AbbVie secured the global commercialization rights
to risankizumab in February 2016 for an upfront payment of $600 million.
Currently, a Phase 3 clinical trial of Skyrizi for the treatment of psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis is
ongoing.

Skyrizi was approved in the United States and the European Union in 2019 for the treatment of adults with
moderate to severe plaque psoriasis.
Skyrizi entered a very crowded market, and the drug competed with a variety of drugs, including: Novartis Cosentyx and Ilaris, Eli Lilly's Taltz, Valeant's Siliq, Johnson & Johnson's Tremfya, Sun Pharmaceuticals' Ilumya and others
.
Among these drugs, Tremfya and Ilumya are also biological therapies
that selectively target IL-23.

However, despite all these competitors, Skyrizi's sales performance was very strong, reaching $2.
939 billion in global sales in 2021, an increase of 84.
9%
over the previous year.
With the success of a series of Phase 3 clinical trials, AbbVie is optimistic that Skyrizi and Rinvoq, another oral anti-inflammatory drug JAK inhibitor, will have sales of $15 billion in 2025, which will be able to make up for the loss
of sales caused by the flagship Humira (Humira, adalimumab) biosimilar competition in the US market since 2023.
(Biovalley Bioon.
com)

AbbVie Announces European Commission Approval of SKYRIZI® (risankizumab) for the Treatment of Moderate to Severe Active Crohn's Disease