Unlocking Approval: Sofie Berg from AbbVie in an Illuminating Dialogue Exchange with PharmaShots

Shots:

Recently, the European Commission approved AbbVie’s Skyrizi for the treatment of adults with moderate to severe active Ulcerative Colitis

The approval was based on positive data from the P-III INSPIRE induction trial and COMMAND maintenance study

Today, at PharmaShots we have Sofie Berg, TA Head of International Immunology at AbbVie, shedding light on the approval

Saurabh: How does this approval fit into AbbVie's broader strategy for treating inflammatory bowel diseases? And what can patients with ulcerative colitis hope for in terms of long-term benefits from SKYRIZI?  

Sofie: AbbVie aims to provide a portfolio of inflammatory bowel disease (IBD) therapies with different mechanisms of action and modes of administration to meet the different needs of patients with IBD. AbbVie now has two efficacious products to offer people living with (both) Crohn’s disease or ulcerative colitis (UC): RINVOQ and SKYRIZI. HCPs can choose the optimal treatment based on a benefit-risk assessment with the patient, and considering the preferred method of administration.

In the Phase 3 SKYRIZI UC clinical trials, INSPIRE and COMMAND, patients treated with SKYRIZI experienced significant improvements in clinical remission and mucosal healing. These are important findings as mucosal healing goes beyond symptom management to restoration of the intestinal lining and is associated with improved long-term outcomes. It has been shown that achieving mucosal healing in UC is associated with an increase in long-term clinical remission, a decreased risk of hospitalization and need for surgery and a decreased impact on work and leisure activities.

Long-term extension studies for SKYRIZI in patients with UC will continue over the next couple of years.

Saurabh: Why are clinical remission and mucosal healing so important for patients with ulcerative colitis? And how does histologic endoscopic mucosal healing (HEMH) help us gauge how well the treatment is working?  

Sofie: Clinical remission in UC includes improvement of disease symptoms as well as mucosal inflammation. Achieving symptom control is an important first step in treating a patient with UC, however, reaching symptom control does not prevent future flares from occurring, so it is important for people living with UC to understand that symptom management alone does not change the course of disease. Achieving mucosal healing is associated with improved outcomes, including long-term clinical remission and reduced risk of hospitalizations and surgeries.

Treatment goals in UC continue to evolve beyond symptom improvement and clinical remission toward mucosal healing. Extensive evidence and the STRIDE II recommendations support that if mucosal healing is not achieved, there may be significant consequences for patients.

HEMH is an endpoint that assesses both the visual appearance of the colon, through endoscopy, and the level of inflammation from biopsies, within the colon. Achievement of HEMH indicates a significant reduction of inflammation within the colon. In the Phase 3 COMMAND study, significantly more patients treated with SKYRIZI 180 mg and 360 mg achieved HEMH at week 52 than those treated with the induction dose only: 43% and 42%, respectively, versus 23%. These results indicate that SKYRIZI is working to heal the intestinal lining – an important long-term treatment goal in UC.

Saurabh: What were the key results from the INSPIRE and COMMAND trials that led to this approval? Also, how did SKYRIZI® perform in terms of safety, and were any new safety concerns discovered during the trials?  

Sofie: The European Commission approval is based on data from two Phase 3 clinical trials: the INSPIRE induction trial and the COMMAND maintenance trial that evaluated the efficacy and safety of SKYRIZI in adults with moderately to severely active UC.

In both trials, the primary endpoint of clinical remission (per Adapted Mayo Score) and key secondary endpoints, including endoscopic improvement, HEMH, mucosal healing and steroid-free clinical remission, were met.

The safety profile of SKYRIZI in both the INSPIRE and COMMAND trials was consistent with the safety profile observed in previous trials across other indications, with no new safety risks observed.

Saurabh: How does SKYRIZI® meet the needs of patients who haven’t had success with conventional or biologic treatments? And what do the Phase 3 trial results say about SKYRIZI®’s effectiveness for those who haven't previously used biologics or JAK inhibitors?  

Sofie: UC is a chronic, unpredictable and sometimes debilitating disease. Despite available treatment options, research has found that many patients with UC are not reaching their long-term treatment targets, and new therapeutic options may be necessary.

In the Phase 3 clinical trials, SKYRIZI was effective as an induction and maintenance therapy for a wide range of patients, including those who are naive to advanced therapy as well as those who have failed one or more advanced therapies.

Specifically, in the INSPIRE induction trial, a significantly higher proportion of patients treated with risankizumab 1,200 mg IV achieved the primary endpoint of clinical remission (per Adapted Mayo Score) at week 12 than patients receiving placebo (20% vs 6%). The positive response was maintained over 52 weeks of treatment, with a significantly higher proportion of patients who received risankizumab 180 mg or 360 mg subcutaneously achieving clinical remission at week 52 than patients in the induction-only control group: 40% and 38%, respectively, versus 25%.

COMMAND, the Phase 3 maintenance trial, included 75% (411/548) of subjects who had failed (inadequate response or intolerance) one or more biologics therapies, JAK inhibitors, and/or S1P receptor modulators prior to induction baseline.

Of the patients without previous biologic or JAK inhibitor failure, SKYRIZI performed especially well for the primary endpoint of clinical remission and key secondary endpoint of mucosal healing. Specifically, 62% of patients who received risankizumab 360 mg and 51% who received risankizumab 180 mg achieved clinical remission versus 31% of patients in the induction-only control group. Similarly, 76% of patients who received risankizumab 360 mg and 60% who received risankizumab 180 mg achieved mucosal healing versus 36% of patients in the induction-only control group.

These findings represent significant improvements in clinical remission and mucosal healing for patients living with UC. These are important findings as mucosal healing goes beyond symptom management to restoration of the intestinal lining and is associated with improved long-term outcomes.

Saurabh: How has the partnership between AbbVie and Boehringer Ingelheim contributed to the development of SKYRIZI®?  

Sofie: SKYRIZI is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally.

Saurabh: What comes next for SKYRIZI® now that it’s approved in the EU? And how does AbbVie plan to keep pushing forward with research to explore new benefits or indications for SKYRIZI? 

Sofie: The approval of SKYRIZI introduces a new treatment option for patients with UC. This is important since the intense symptoms of UC can disrupt a patient’s quality of life, and living with UC comes with significant personal health costs. As a next step in the EU, we will continue to work on obtaining access to SKYRIZI for patients with UC.

Multiyear trials, including sub-analyses, for SKYRIZI in UC and Crohn’s disease are ongoing, and we look forward to sharing those results with the scientific community in upcoming congresses and scientific journals.

We remain committed to bringing new treatment options to patients in need through ongoing research and development in gastroenterology.

Image Source: Canva

About the Author:

Sofie Berg

Sofie Berg, Pharm.D, PhD., is the therapeutic area head of international immunology, International Medical Affairs, at AbbVie. Her team is responsible for late-stage pipeline and on-market assets within the immunology franchise. Sofie’s background is in gastroenterology, and she has been working in this field since earning her Ph.D. in gastroenterology approximately 20 years ago. Sofie is deeply engaged with hearing patients’ stories and the unmet needs impacting them.