Takeda Pharmaceutical Company Limited announced that two interim reports from the ongoing, open-label GEMINI long-term safety (LTS) study describing clinical data of long-term Entyvio (vedolizumab) treatment in patients with moderately to severely active ulcerative colitis (UC) and moderately to severely active Crohn's disease (CD) have been published in the Journal of Crohn's & Colitis.
The data showed that patients with moderately to severely active UC experienced clinical and health-related quality of life (HRQL) improvements with continued vedolizumab treatment. For patients with moderately to severely active CD, the clinical benefits of vedolizumab continued with long-term treatment regardless of prior TNF antagonist exposure. UC and CD patients that entered the study after discontinuing prior eight-weekly maintenance dosing due to loss of clinical response, in GEMINI I and II respectively, could experience a beneficial effect with increasing dosing frequency to every four weeks.
GEMINI LTS is an ongoing, single-arm, open-label phase 3 extension study, with a primary objective of evaluating the safety profile of long-term vedolizumab treatment. Enrolled patients included those who completed or withdrew early from the double-blind, randomized, placebo-controlled phase 3 studies GEMINI I and II. The interim reports published in the Journal of Crohn's & Colitis represent efficacy data collected from May 22, 2009 to June 27, 2013. Outcomes of clinical response, remission and HRQL were assessed for up to 152 weeks of treatment in the efficacy population.
"Given that ulcerative colitis and Crohn's are chronic diseases, it is imperative we evaluate a treatment's efficacy and safety over the long-term to assess its continued benefit for patients," Edward V. Loftus, MD, Professor of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. "These latest findings, reflecting continuous use of vedolizumab for up to three years, are encouraging and provide additional information about the potential benefit for vedolizumab as a long-term treatment option for people with ulcerative colitis and Crohn's disease."
About the Interim Analysis
GEMINI LTS Ulcerative Colitis Analysis
A total of 894 patients with UC were enrolled in the GEMINI LTS study and constituted the safety population, and a subset of 845 patients with moderately to severely active UC constituted the efficacy population.
As of June 27, 2013, 63 percent of the efficacy population (n=532/845) were continuing treatment. Among patients who responded to vedolizumab induction and had data available, 88 percent (n=120/136) were in remission after 104 weeks of exposure (96 percent [n=70/73] after 152 weeks). Among patients who withdrew from every-8-week vedolizumab maintenance in GEMINI I (n=32) before week 52, increased dosing to every 4 weeks in GEMINI LTS resulted in response and remission rates of 41 percent and 28 percent, respectively, after 52 weeks, an increase from 19 percent and 6 percent, respectively, from before the dose increase. Similar benefits were demonstrated regardless of prior TNF antagonist exposure. Durable benefits on HRQL were also observed.
GEMINI LTS Crohn's Disease AnalysisA total of 1,349 patients with CD enrolled in the GEMINI LTS study and constituted the safety population. The efficacy population comprised 1,297 patients with moderately to severely active CD: 700 from GEMINI II, 372 from GEMINI III, and 225 vedolizumab-naïve patients.
Among patients with response at week 6 in GEMINI II who received vedolizumab continuously, 83 percent (n=100/120) and 89 percent (n=62/70) of patients with available data were in remission after 104 and 152 weeks, respectively. Increased dosing frequency from every 8 weeks (GEMINI II) to every 4 weeks (GEMINI LTS) improved outcomes in patients who had withdrawn early from GEMINI II, with 47 percent (n=27/57) experiencing clinical response and 32 percent (n=18/57) in remission at week 52 of GEMINI LTS (up from 39 percent and 4 percent before the dose increase). Similar improvements were observed regardless of prior TNF antagonist exposure. Long-term benefits of HRQL were also observed.
Patients who were previously exposed to vedolizumab in the GEMINI II and GEMINI III trials demonstrated a reduction in disease activity which was sustained with long-term open-label vedolizumab therapy. After an additional 100 weeks (week 152) of treatment, 74 percent (n=156/212) of all patients who completed GEMINI II were in remission including 66 percent (n=75/113) of those with prior TNF antagonist failure and 82 percent (n=69/84) of TNF antagonist naïve patients. Long-term benefits of HRQL were also observed.
"This latest data from GEMINI LTS provide clinicians and patients valuable information regarding the durability of treatment response to vedolizumab over time," said Michael Smyth, Executive Medical Director, Takeda Pharmaceuticals. "At Takeda, we are committed to continuing this important research to further characterize vedolizumab's benefit: risk profile as a treatment option for patients with moderately to severely active ulcerative colitis and Crohn's disease."
Vedolizumab is a gut-selective humanized monoclonal antibody, approved in over 50 countries. It is the first and only biologic therapy to be approved simultaneously for the treatment of adults with moderately to severely active UC or CD who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha antagonist.
Article: Long-term Efficacy of Vedolizumab for Ulcerative Colitis, Edward V. Loftus Jr, Jean-Frédéric Colombel, Brian G. Feagan, Severine Vermeire, William J Sandborn, Bruce E. Sands, Silvio Danese, Geert R. D'Haens, Arthur Kaser, Remo Panaccione, David T. Rubin, Ira Shafran, Megan McAuliffe, Arpeat Kaviya, Serap Sankoh, Reema Mody, Brihad Abhyankar, Michael Smyth, Journal of Crohn's & Colitis, doi: 10.1093/ecco-jcc/jjw177, published online 28 September 2016.