Sanofi and Teva's Duvakitug Shows Sustained Efficacy in Phase 2b Maintenance Study for Inflammatory Bowel Disease
核心洞察
Duvakitug, a TL1A (搜索)-targeting monoclonal antibody, demonstrated durable clinical and endoscopic efficacy over 44 weeks in patients with ulcerative colitis (搜索) and Crohn's disease (搜索) who initially responded to induction therapy.
In the maintenance study, 58% of ulcerative colitis (搜索) patients achieved clinical remission with the 900 mg dose, while 55% of Crohn's disease (搜索) patients achieved endoscopic response at the same dose level.
The therapy was well tolerated with safety profiles consistent with the induction study, reinforcing its potential as a best-in-class treatment for inflammatory bowel disease (搜索).
Positive results from the RELIEVE UCCD long-term extension study demonstrate that duvakitug, an investigational human monoclonal antibody targeting TL1A (搜索), maintained durable clinical and endoscopic efficacy over 44 weeks in patients with ulcerative colitis (搜索) (UC) and Crohn's disease (搜索) (CD) who initially responded to induction therapy. The findings reinforce the therapeutic potential of this novel approach to treating inflammatory bowel disease (搜索) (IBD (搜索)).
Sustained Clinical Benefits Across Both IBD Subtypes
The double-blind randomized maintenance study enrolled 130 patients who had responded to duvakitug during the 14-week RELIEVE UCCD induction phase. Participants were re-randomized to receive either 450 mg or 900 mg subcutaneous doses of duvakitug every four weeks throughout the 44-week maintenance period.
At week 44, the higher 900 mg dose demonstrated superior efficacy across both disease types. In ulcerative colitis (搜索) patients, 58% achieved the primary endpoint of clinical remission per the modified Mayo score, compared to 47% with the 450 mg dose. For Crohn's disease (搜索) patients, 55% achieved endoscopic response as defined by the Simple Endoscopic Score for CD with the 900 mg dose, versus 41% with the lower dose.
"One of the persistent challenges in treating ulcerative colitis (搜索) and Crohn's disease (搜索) isn't just achieving an initial response, but sustaining it," said Eric Hughes, MD, PhD, Executive Vice President, Global R&D and Chief Medical Officer at Teva (搜索). "These Phase 2b results further reinforce TL1A (搜索) as a compelling target and clearly strengthen the case that duvakitug has the potential to be a best-in-class therapy."
Favorable Safety Profile Maintained
Both doses of duvakitug were well tolerated throughout the extended treatment period. The most frequently observed adverse events (≥5% of all patients) with pooled duvakitug doses included upper respiratory tract infection, nasopharyngitis, Crohn's disease (搜索), and hypertension. Importantly, the safety profile remained consistent with that observed during the induction study, suggesting no emergence of new safety signals with prolonged exposure.
Novel Mechanism Targets Key Inflammatory Pathway
Duvakitug represents a novel therapeutic approach through its selective targeting of TL1A (搜索) (TNF-like ligand 1A), a cytokine believed to amplify inflammation and drive fibrosis (搜索) associated with IBD (搜索) through binding to its receptor, DR3 (搜索). The monoclonal antibody preferentially inhibits TL1A-DR3 signaling over DcR3 (搜索) (decoy receptor 3) binding, with the potential to reduce both inflammation and fibrosis.
The RELIEVE UCCD program utilized an innovative basket study design, allowing inclusion of patients with either UC or CD. Notably, this represents the first and only randomized, blinded, and placebo-controlled phase 2 study to investigate the impact of TL1A (搜索) inhibition in Crohn's disease (搜索).
Addressing Significant Unmet Medical Need
IBD (搜索) affects approximately 4.9 million people globally, with incidence rising in several regions. The autoimmune disorder is characterized by chronic inflammation of the gastrointestinal tract, with UC and CD representing the two most common forms. Both conditions follow repetitive cycles of relapses and remission, presenting symptoms including persistent diarrhea, rectal bleeding, abdominal pain, loss of appetite, and weight loss.
Prolonged inflammation can lead to serious complications, including fibrosis (搜索) characterized by excessive accumulation of scar tissue in the intestinal wall, potentially causing narrowing and obstruction. Currently, no cure exists for IBD (搜索), with treatment goals focused on inducing and maintaining remission while preventing flares.
Strategic Partnership Advances Development
The collaboration between Teva (搜索) and Sanofi involves equal sharing of global development costs and net profits and losses in major markets. Sanofi leads the phase 3 clinical development program, while Teva will lead commercialization in Europe, Israel, and specified other countries. Sanofi will handle commercialization in North America, Japan, other parts of Asia, and the rest of the world.
"These results reinforce duvakitug's potential as a leading TL1A (搜索) therapy and an important advancement in inflammatory bowel disease (搜索) treatment with durable efficacy maintained for nearly one year in patients living with ulcerative colitis (搜索) or Crohn's disease (搜索)," said Houman Ashrafian, Executive Vice President, Head of Research and Development at Sanofi. "With phase 3 studies underway, we're committed to advancing duvakitug for patients who need new options, and it remains a key opportunity in our pipeline."
The companies plan to present detailed results from the study at an upcoming medical meeting, while phase 3 clinical studies for both UC and CD are currently underway. The sustained efficacy demonstrated in this maintenance study provides strong support for the ongoing late-stage development program and the potential for duvakitug to address significant unmet needs in IBD (搜索) treatment.