Novel Combination Therapy of IL-23 and TNFα Antagonists (Tremfya + Simponi) Demonstrates Superior Efficacy Over Monotherapy in Ulcerative Colitis

News on February 21, 2022 /BioValleyBIOON/ -- Johnson & Johnson (JNJ) subsidiary Janssen Pharmaceuticals recently presented data from the proof-of-concept Phase 2a VEGA study (NCT03662542; EudraCT 2018-001510-15) of Tremfya (Tremfya, generic name: guselkumab) in combination with Simponi (Simponi, generic name: golimumab) for the treatment of adult patients with moderate to severe active ulcerative colitis (UC) at the 17th European Crohn's and Colitis Organisation (ECCO) Congress 2022. Tremfya is a selective IL-23p19 subunit antagonist and is not yet approved for the treatment of UC. Simponi is aTumorTumor Necrosis Factor-alpha (TNF-α) antagonists have been approved for the treatment of UC.

Results:At Week 12 of treatment, compared with Tremfya or Simponi monotherapy, the combination therapy of Tremfya + Simponi induced higher rates of clinical response, clinical remission, endoscopic improvement, and composite histologic-endoscopic endpoints. The incidence of adverse events (AEs) was comparable across the treatment groups.

The next step in evaluating Tremfya + Simponi combination therapy for UC is the Phase 2b DUET-UC study, a one-year dose-ranging study that will compare combination therapy with monotherapy.

Jan Wehkamp, Head of Gastroenterology at Janssen Research & Development, said: "VEGA is the first study in its class to evaluate the combination of an IL-23p19 subunit antagonist with a TNFα antagonist for the treatment of UC."The results from this study enable us to further explore and identify areas of unmet needs among patients. We are encouraged by the insights gained from the collaborative research as they can help us redefine treatment for patients with immune-mediated diseases, such as ulcerative colitis."

VEGA is a randomized, double-blind, positive drug-controlled, parallel-group, global multicenter Phase 2a study conducted in patients with moderate to severe active UC. These patients had a Mayo score of 6-12, an endoscopy subscore ≥2, were previously untreated with TNFα antagonists (TNF-α naive), and were refractory or intolerant to conventional therapies (such as immunomodulators and/or corticosteroids). In the study, these patients were randomly assigned to receive Tremfya monotherapy (n=71), Simponi monotherapy (n=72), or Tremfya+Simponi combination therapy (n=71).

The primary endpoint of the study was clinical response at week 12, defined as a reduction from baseline in the Mayo score of ≥30% and ≥3 points, with a decrease in the rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1. The key secondary endpoint was clinical remission at week 12, defined as a Mayo score of ≤2, with no individual subscore >1. No adjustments were made for multiple comparisons in the study. Other key endpoints assessed at week 12 included clinical remission (based on components of the modified Mayo score), symptomatic remission, endoscopic improvement, endoscopic normalization, histologic remission, composite histologic-endoscopic endpoints, and others.BiomarkerResults.

The 12-week results of the study showed:

-- Clinical Response: Patients receiving combination therapy had a higher clinical response rate, with 83.1% in the Tremfya + Simponi combination therapy group, 74.6% in the Tremfya monotherapy group, and 61.1% in the Simponi monotherapy group.

--Clinical Remission: According to the Mayo score, patients receiving combination therapy had a higher clinical remission rate, with rates of 36.6%, 21.1%, and 22.2% in the Tremfya+Simponi combination therapy group, Tremfya monotherapy group, and Simponi monotherapy group, respectively. Additionally, based on the modified Mayo score, patients receiving combination therapy also showed a higher clinical remission rate, with rates of 46.5%, 23.9%, and 25% in the Tremfya+Simponi combination therapy group, Tremfya monotherapy group, and Simponi monotherapy group, respectively.

——Endoscopic results: Patients receiving combination therapy had a higher endoscopic improvement rate, with rates of 49.3%, 29.6%, and 25% in the Tremfya+Simponi combination therapy group, Tremfya monotherapy group, and Simponi monotherapy group, respectively.

——Proportion of patients with normalized endoscopy: The combination therapy group is almost twice that of the monotherapy group, with 18.3% in the Tremfya+Simponi combination therapy group, 8.5% in the Tremfya monotherapy group, and 9.7% in the Simponi monotherapy group.

——Composite histologic and endoscopic outcomes: 40.8% of patients in the Tremfya + Simponi combination therapy group achieved the composite endpoint of histologic remission and endoscopic improvement, compared to 26.8% in the Tremfya monotherapy group and 15.3% in the Simponi monotherapy group.

At week 12, the rate of symptom relief (based on patient-reported rectal bleeding and stool frequency [SF]), histological remission rate,BiomarkerNormalization rates (calprotectin, C-reactive protein) were also higher.

The incidence of key safety events was similar across treatment groups. The incidence of adverse events in the combination therapy group, Tremfya monotherapy group, and Simponi monotherapy group was 40.8%, 43.7%, and 52.8%, respectively. The incidence of serious adverse events was 1.4%, 2.8%, and 1.4%, respectively. The infection rates in the combination therapy group, Tremfya monotherapy group, and Simponi monotherapy group were 14.1%, 14.1%, and 22.2%, respectively. No deaths or malignancies were reported within 12 weeks of the study.TumorOr tuberculosis cases. One patient receiving combination therapy simultaneously developed severe influenza and sepsis infection. (Bioon.com)

Source of Original Text:Results of Novel Clinical Study Show Adults with Moderately to Severely Active Ulcerative Colitis Achieved Higher Rates of Clinical Response, Clinical Remission, and Endoscopic Improvement at 12 Weeks with Guselkumab and Golimumab Combination Therapy Versus Either Monotherapy Alone