Clinical Trials

Date: 2017-06-16

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the European League Against Rheumatism Annual Congress (EULAR 2017)

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: active psoriatic arthritis

Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases

Country: Belgium, Bulgaria, Canada, Czech Republic, Estonia, France, Japan, Mexico, The Netherlands, Poland, Russian Federation, Spain, Ukraine, UK, USA

Trial details:

• SPIRIT-P1 is a Phase 3 randomized, active- and placebo-controlled study examining the effect of ixekizumab compared with placebo in patients with active PsA who are bDMARD-naïve. Patients were required to have an established diagnosis of PsA and active disease for at least six months. During the study, ixekizumab-treated patients received a starting dose of 160 mg administered subcutaneously (SC), followed by one of two dosing regimens: either 80 mg administered SC once every two weeks or 80 mg administered SC once every four weeks. Adalimumab at the approved dose of 40 mg SC and regimen of every other week was selected as the active control for comparison with placebo. The SPIRIT-P1 study will also evaluate the long-term efficacy and safety of ixekizumab in PsA for up to three years. (NCT01695239)

Latest news:

• • On June 16, 2017, Eli Lilly announced that the majority of patients with active psoriatic arthritis treated with Taltz® (ixekizumab) exhibited either no progression or minimal progression of radiographic structural joint damage through 52 weeks of treatment. Detailed results from the extension period of the SPIRIT-P1 trial have been presented in an oral presentation today during the Annual European Congress of Rheumatology (EULAR) 2017.
• During the 24-week, double-blind period of the SPIRIT-P1 study, patients with active PsA who had never received a biologic disease-modifying antirheumatic drug were treated with either 80 mg of Taltz® once every two weeks or every four weeks (following a 160-mg starting dose), or adalimumab at the approved dose of 40 mg every two weeks or placebo. Adalimumab was employed as an active control in the SPIRIT-P1 study and was not powered for comparison with Taltz treatment groups. Following completion of the 24-week treatment period, patients were re-randomized to receive 80 mg of Taltz® every two weeks or four weeks to evaluate response rates during the extension period through 52 weeks.
• Patients treated with Taltz® at both dosing regimens experienced either no progression or minimal radiographic progression of structural joint damage as measured by the change from baseline in the van der Heijde modified Total Sharp Score (mTSS) for PsA at 52 weeks. No progression or minimal radiographic progression of structural joint damage was also observed for patients who switched from placebo or adalimumab to either dosing regimen of Taltz® after the 24-week treatment period.
• During the extension period of SPIRIT-P1, the incidence of treatment-emergent adverse events was greater with Taltz® treatment compared with placebo. The most common (?4 percent) treatment-emergent adverse events observed in all patients treated with Taltz® were nasopharyngitis and injection site reaction. These events are consistent with those reported in the Phase 3 studies of Taltz® for the treatment of moderate-to-severe plaque psoriasis (UNCOVER 1, 2, 3).
• Lilly has filed a supplemental Biologics License Application (sBLA) with the FDA for Taltz® as a treatment of adult patients with active PsA. Taltz® is approved for adult patients with active PsA in Japan. Submissions to other regulatory agencies around the world are expected later this year.
• • On November 8, 2015, Eli Lilly announced that psoriatic arthritis (PsA) patients treated with ixekizumab for 24 weeks achieved significant improvements in signs and symptoms of their disease when compared to placebo, while also experiencing significantly less progression of radiographic structural joint damage, reduced disability when performing certain physical functions and improved skin clearance of plaque psoriasis.
• Detailed results of the SPIRIT-P1 study were presented during the American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting in San Francisco. During the 24-week, double-blind period of this Phase 3 study, patients who had never received a biologic disease-modifying antirheumatic drug (bDMARD) were treated with either 80 mg of ixekizumab once every two weeks or every four weeks (following a 160 mg starting dose); adalimumab at the approved dose of 40 mg every other week; or placebo. Adalimumab was employed as an active control in the SPIRIT-P1 study and was not powered for comparison with ixekizumab treatment groups. In both dosing regimens, ixekizumab-treated patients demonstrated significant improvements compared with placebo in disease activity of PsA as demonstrated by the proportion of patients achieving an ACR20 response at 24 weeks, the study's primary objective. Improvements were experienced by ixekizumab-treated patients as early as one week after treatment initiation. ACR20 represents at least a 20 percent reduction in a composite measure of disease activity as defined by the ACR. Other measures included ACR50 and ACR70, which represent 50 percent and 70 percent reductions in disease activity.
• At 24 weeks, 62 percent of patients treated every two weeks and 58 percent of patients treated every four weeks with ixekizumab achieved ACR20 compared with 30 percent of placebo-treated patients. The proportions of ixekizumab-treated patients who achieved ACR50 when treated every two weeks or every four weeks were 47 percent and 40 percent, respectively, compared with 15 percent of patients treated with placebo. Furthermore, 34 percent of patients treated with ixekizumab every two weeks and 23 percent of those treated every four weeks experienced a 70 percent reduction in disease activity. Six percent of patients treated with placebo achieved this level of improvement.
• Patients treated with ixekizumab at both dosing regimens also experienced significantly less radiographic progression of structural joint damage than those treated with placebo, as measured by the change from baseline in the van der Heijde modified total Sharp score (mTSS) for PsA at 24 weeks. Structural joint damage caused by PsA may lead to permanent joint deformity and reduced physical function. Ixekizumab treatment groups also experienced significant improvements compared with placebo in other key secondary measures, including physical function as assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI), and improved skin clearance of plaque psoriasis as measured by the Psoriasis Area and Severity Index (PASI), including PASI75, 90 and 100. A PASI75 score indicates at least a 75 percent reduction in a patient's plaque psoriasis from the patient's baseline assessment, while PASI90 reflects a 90 percent reduction and PASI100 represents a 100 percent reduction, reflecting complete skin clearance.
• Efficacy results with adalimumab compared with placebo during the SPIRIT-P1 study were significant on most measures. At 24 weeks, 57 percent of patients treated with adalimumab, the study's active control, achieved ACR20, while 39 percent and 26 percent achieved ACR50 and ACR70, respectively.
• The incidence of treatment-emergent adverse events (TEAE) was greater with ixekizumab treatment compared with placebo. The most common (?4 percent) adverse events observed with ixekizumab treatment were injection site reaction, injection site erythema and nasopharyngitis. These events are consistent with those reported in the Phase 3 studies of ixekizumab for the treatment of moderate-to-severe plaque psoriasis (UNCOVER 1, 2, 3). Serious adverse events and discontinuation rates due to adverse events were not significantly different between treatment groups.
• • On April 20, 2015, Eli Lilly announced that ixekizumab was statistically superior to placebo in the treatment of patients with active psoriatic arthritis (PsA), as demonstrated by the proportion of patients achieving an ACR 20 response. ACR 20 is a standard assessment that represents a 20 percent reduction in disease signs and symptoms as defined by the American College of Rheumatology response criteria. During the 24-week, Phase 3 study, titled SPIRIT-P1, patients who were naïve to biologic disease-modifying antirheumatic drugs (bDMARD) were treated with one of two different ixekizumab dosing regimens or placebo. In both dosing regimens, ixekizumab-treated patients demonstrated significant improvements versus placebo in signs and symptoms of active PsA. In SPIRIT-P1, the incidence of treatment-emergent adverse events was more frequent with ixekizumab compared with placebo. The most common adverse events observed were consistent with the Phase 3 studies of ixekizumab for the treatment of moderate-to-severe plaque psoriasis. The rates of serious adverse events with ixekizumab treatment were similar to placebo. Discontinuation rates due to adverse events were similar between treatment groups. Lilly plans to submit detailed data from the SPIRIT-P1 study for disclosure at scientific meetings and in peer-reviewed journals.

     

Is general: Yes