Together PSO Trial - Combination Ixekizumab and Tirzepatide Save

Today Lilly announced top line results of the TOGETHER-PsO open-label, Phase 3b trial demonstrating the significant benefits of concomitant ixekizumab (IXE: an IL-17A inhibitor) and tirzepatide (TIR: GLP-1agonist) over IXE alone.

This report comes on the heels of the recently announced 271 patient, phase 3b "TOGETHER PsA" trial, demonstrating the superiority of the combination use of ixekizumab (Taltz) and tirzepatide (Zepbound) over IXE alone, with the primary endpoint (ACR50 and >10% weight loss) favoring combination therapy (31.7%) over IXE (0.8%) at 36 weeks.

The TOGETHER-PsO trial was a 36 week trial that enrolled patients with moderate-to-severe plaque psoriasis and obesity or overweight with at least one additional weight-related comorbid condition. At 36 weeks, the combination met both primary and all key secondary endpoints, delivering superior skin clearance and weight loss compared to IXE monotherapy.

These findings are significant for the psoriatic population In the U.S., where approximately 61% of people with psoriasis also have obesity or overweight with at least one weight-related comorbidity,  Obesity and an increase in BMI has been shown to reduce the odds of reaching skin clearance across multiple psoriasis studies. The study enrolled a population with a very high burden of disease that is often associated with poorer treatment outcomes, with an average BMI of more than 39 kg/m2 across both treatment arms. 

The primary endpoint in this was achieving both a PASI 100 (Psoriasis Area Severity Index) and >10% weight loss. This was seen in 27.1% on IXE and TIR, compared to 5.8% IXE alone (p<0.001). Looking at PASI 100 alone, the combination outperformed monotherapy (40.6% vs. 29%, p<0.05). 

Most patients in the TOGETHER-PsO trial had extensive skin involvement, with approximately 25% of their body surface area affected, and nearly all (97%) had psoriasis affecting high-impact body areas linked to significant morbidity, itch, and skin pain, such as the face, scalp or genitals. 

Adverse events in participants treated with combination therapy were generally mild to moderate, and the types of adverse events were generally consistent with the known safety profile of each medicine. The most common adverse events occurring in ≥5% of participants were nausea, diarrhea, constipation, injection site reaction, dosing error, vomiting, and dizziness in the IXE and TIR concomitant treatment arm, and injection site reaction, dosing error, and nasopharyngitis in the IXE monotherapy arm.