Jyseleca in UC
UC is an inflammatory bowel disease resulting in ulcerations and inflammation of the inner layer of the colon and rectum. The current market for UC treatments is estimated at ~€1.0 billion in the five largest European markets.
Biologic therapies for UC were dominated by tumor necrosis factor (TNF) antagonists for nearly 20 years, but anti-integrin and anti-interleukin (IL)-12/IL-23 antibodies have recently become available. Although the introduction of advanced therapies has improved the treatment of some patients, 30% of patients do not respond to treatment,1 and 19% to 59% of initial responders don’t have a sustainable treatment response.2,3 Therefore, the medical need for improved treatment efficacy with additional treatment options remains high.
Commercialization and regulatory progress of Jyseleca in UC
Following approval of Jyseleca (200mg) for the treatment of adults with moderate to severe UC in the European Union in 2021 and in January 2022 in Great Britain, Jyseleca is now launched in UC in Germany and the Netherlands, with roll-out throughout the rest of Europe anticipated this year.
The European Summary of Product Characteristics for filgotinib, which includes contraindications and special warnings and precautions, is available at www.ema.europa.eu. The individual Great Britain and Northern Ireland Summary of Product Characteristics can be found at www.medicines.org.uk/emc and www.emcmedicines.com/en-GB/northernireland respectively.
Gilead is responsible for Jyseleca outside Europe and submitted the new drug application in Japan for filgotinib in UC to the Pharmaceuticals and Medical Devices Agency (PMDA) in the first half of 2021. A decision on its potential approval is anticipated in the first half of 2022.
Safety and efficacy in the filgotinib UC development program
Filgotinib 200mg has shown favorable results in terms of rapid onset of action, efficacy, safety, and tolerability from the SELECTION Phase 3 program in patients with moderate to severe UC. The SELECTION Phase 3 data (Feagan et al. 2021) were published in The Lancet.
Both in biologic-naïve and in biologic-experienced patients a rapid onset of action for filgotinib 200mg at week 2, with a sustained effect up to 10 weeks, was observed in a pre-specified exploratory analysis of the SELECTION study. The graph below shows the rapid onset in both cohorts using the partial Mayo Clinic Score.
Additionally, data from a post hoc analysis of the maintenance study showed a greater proportion of biologic-naïve and biologic-experienced patients receiving filgotinib 200mg maintained clinical remission up to 58 weeks versus those receiving placebo (37% versus 11% p<0.001) and had histologic remission (38% versus 13% p<0.001), 6-month corticosteroid-free clinical remission (27% versus 6% p<0.01), as shown in the graph below, and published in The Lancet (Feagan et al. 2021).
We presented a set of new data from the SELECTION study and SELECTION long-term extension study in UC at the European Crohn’s and Colitis Organisation (ECCO) 2022 annual conference. The key findings were:
- Continued treatment with filgotinib for up to additional 96 weeks in the long-term extension study was effective in maintaining long-term improvements in UC symptoms;
- Retreatment with filgotinib upon interruption, resulted in recovery of efficacy in most patients and that filgotinib was well tolerated with no new safety concern;
- Filgotinib's efficacy profile was consistent and the safety profile acceptable regardless of the age group, analysing patients with up to 75 years of age;
- Filgotinib was able to achieve the high bar of efficacy as defined by a combined endpoint of clinical and quality of life (QoL) remission, endoscopic and biomarker improvement.
Furthermore, additional safety data from the SELECTION studies were presented at the 16th European Crohn’s and Colitis Organisation (ECCO) 2021 virtual congress (Schreiber et al. 2021). Data were analyzed from the SELECTION induction, maintenance, and long-term extension study with a cumulative treatment exposure of 1,207 patient years for filgotinib 200mg versus 318 patient years for placebo, showing results consistent with the original induction and maintenance studies, where filgotinib was well tolerated in patients with moderately to severely active UC.
1 1Allez M et al. Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: definitions, frequency and pharmacological aspects. J Crohns Colitis. 2010 Oct;4(4):355-66;
2, 2,Ma C et al. Outpatient Ulcerative Colitis Primary Anti-TNF Responders Receiving Adalimumab or Infliximab Maintenance Therapy Have Similar Rates of Secondary Loss of Response. J Clin Gastroenterol. 2015 Sep;49(8):675-82;
3 3Ma C et al. Outpatient Ulcerative Colitis Primary Anti-TNF Responders Receiving Adalimumab or Infliximab Maintenance Therapy Have Similar Rates of Secondary Loss of Response. J Clin Gastroenterol. 2015 Sep;49(8):675-82;