Date: 2015-06-10
Type of
information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in The Lancet
Company: Eli Lilly (USA - IN)
Product: ixekizumab
Action
mechanism:
- monoclonal antibody. Ixekizumab is a monoclonal antibody with high affinity and specificity that binds to and neutralizes the pro-inflammatory cytokine interleukin-17A (IL-17A). In psoriasis, IL-17A plays a major role in driving excess keratinocyte (skin cell) proliferation and activation. Ixekizumab does not bind to cytokines IL-17B, IL-17C, IL-17D, IL-17E or IL-17F. Ixekizumab is administered via subcutaneous injection (under the skin). Ixekizumab is also in clinical development for the treatment of psoriatic arthritis.
Disease: moderate-to-severe plaque psoriasis
Therapeutic
area: Autoimmune diseases - Dermatological diseases
Country: Australia, Austria, Bulgaria, Canada, Czech Republic, France, Denmark, Germany, Hungary, India,Italy, Mexico, The Netherlands, Poland, Romania, Spain, UK, USA
Trial
details:
- UNCOVER-2 and UNCOVER-3 are double-blind, multicenter, Phase III studies evaluating more than 2,500 patients with moderate-to-severe psoriasis in 18 countries. In these comparator studies, patients were assigned to receive either placebo, etanercept (50 mg twice a week) or ixekizumab (80 mg every two or four weeks) for 12 weeks, following a 160 mg starting dose. Patients enrolled in the UNCOVER-2 and 3 studies had a confirmed diagnosis of chronic plaque psoriasis for at least six months prior to randomization. Additionally, at screening and at randomization, they demonstrated at least 10 percent Body Surface Area (BSA) of psoriasis, an sPGA score of at least 3 and PASI score of at least 12. (NCT01474512 and NCT01646177)
Latest
news:
- • On June 10, 2015, Eli Lilly announced that detailed results of two pivotal Phase III studies for ixekizumab were published by The Lancet. The UNCOVER-2 and UNCOVER-3 clinical studies of more than 2,500 patients found ixekizumab to be statistically superior to etanercept and placebo on all measures of skin clearance. Patients treated with ixekizumab also demonstrated significant and meaningful improvements in health-related quality-of-life measures. In each study, co-primary efficacy objectives assessed whether ixekizumab administered once every two weeks or once every four weeks was superior to etanercept and placebo after twelve weeks, as measured by a Psoriasis Area and Severity Index reduction of at least 75 percent (PASI 75) and a Static Physician Global Assessment score of clear or minimal (sPGA 0/1).
- PASI is a measure used by healthcare professionals to determine the severity of psoriasis, including redness, thickness, scaling and the extent of psoriasis coverage. A PASI 75 score signals at least a 75 percent reduction in a patient's psoriasis from their baseline assessment. The sPGA is the physician's assessment of severity of a patient's psoriasis lesions overall at a specific point in time.
- Rapid Onset of Efficacy; High Levels of Skin Clearance: In both studies and at both dosing regimens, ixekizumab achieved superiority to etanercept and placebo for PASI 75 at week 12, with statistically significant differences seen as early as the first week of the studies. Approximately 50 percent of all ixekizumab-treated patients achieved PASI 75 by week four.
- Patients treated with ixekizumab also achieved higher rates of skin clearance as measured by PASI 90 and PASI 100 compared with etanercept and placebo. PASI 90 reflects at least a 90 percent reduction in psoriasis symptoms, while PASI 100 is the highest possible reduction, representing complete skin clearance. Patients treated with ixekizumab were five to seven times more likely to achieve a PASI 100 score than with etanercept. At the end of the 12-week study period, patients achieved PASI 90 and PASI 100 at the following rates:
- Patients receiving ixekizumab every two weeks: 71 percent in UNCOVER-2 and 68 percent in UNCOVER-3 achieved PASI 90; 41 percent in UNCOVER-2 and 38 percent in UNCOVER-3 achieved PASI 100;
Patients receiving ixekizumab every four weeks: 60 percent in UNCOVER-2 and 65 percent in UNCOVER-3 achieved PASI 90; 31 percent in UNCOVER-2 and 35 percent in UNCOVER-3 achieved PASI 100;
Patients receiving etanercept: 19 percent in UNCOVER-2 and 26 percent in UNCOVER-3 achieved PASI 90; 5 percent in UNCOVER-2 and 7 percent in UNCOVER-3 achieved PASI 100.
Quality-of-Life Measures Significantly Improved: Clinical improvements in ixekizumab-treated patients were accompanied by rapid improvements in health-related quality-of-life measures. Nearly 60 percent of ixekizumab-treated patients reported that their psoriasis had no impact on their quality of life by week 12 as measured by the Dermatology Life Quality Index (DLQI). The DLQI is a standardized tool that evaluates how psoriasis affects various aspects of a person's quality of life, including itching, ability to conduct daily activities, and relationships and intimacy.
- In a separate, pre-specified analysis evaluating patients that had achieved PASI 100, 78 percent in UNCOVER-2 and 85 percent in UNCOVER-3 reported the disease had no impact to their quality of life as measured by the DLQI.
- Adverse Events: The overall rates and severities of adverse events observed were comparable to those for etanercept in the two active comparator trials. Most Treatment-Emergent Adverse Events (AEs) were mild or moderate in severity. The most common (?2 percent) Treatment-Emergent AEs in ixekizumab-treated patients were upper respiratory tract infections, injection site reactions, itching, headache and arthralgia. Serious Adverse Events (SAEs) were reported by < 2 percent of patients, and there were no deaths in either study. Rates of SAEs and discontinuations due to AEs were comparable across treatment groups.
- (Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials.
Is
general: Yes
