Lilly takes its turn in the IL-17 psoriasis data game
This article was originally published in Scrip
Eli Lilly has followed AstraZeneca and Novartis in releasing promising data for a novel drug acting on interleukin-17 in plaque psoriasis, saying its candidate, ixekizumab, has succeeded in the Phase III UNCOVER studies.
Top-line data show that ixekizumab beat placebo and mainstay psoriasis therapy Enbrel (etanercept) using the PASI 75 and PASI 100 skin clearance measures in patients with moderate-to-severe disease at 12 weeks in the three trials.
Lilly says it will present the full data this year and submit regulatory filings next year.
The subcutaneous monoclonal antibody product targets the pro-inflammatory cytokine interleukin-17A (IL-17A), which plays a major role in driving excess keratinocyte proliferation and activation.
But it is competing with Novartis's secukinumab, which is leading the anti-IL17 charge in psoriasis, as well as AstraZeneca/Amgen's brodalumab, and pivotal results already have been reported for both of these drugs.
In May, Amgen and AstraZeneca released data from the first of their three Phase III trials for brodalumab, AMAGINE-1, results that some said might outshine those of leader secukinumab (scripintelligence.com, 10 May 2014).
Data are expected later this year from the AMAGINE-2 and AMAGINE-3 studies, which will assess the monoclonal antibody versus another major new psoriasis product, Stelara (ustekinumab). However, he Janssen IL-12 and IL-23 antagonist has the advantage of a favorable dosing schedule with a subcutaneous injection administered every 12 weeks after initial dosing at weeks zero and four.
Last year, Novartis's Phase III FIXTURE study of secukinumab showed it provided faster, stronger and longer lasting effects on disease symptoms than Enbrel, with a favorable safety profile, and this product is now awaiting US and EU approval (scripintelligence.com, 3 October 2013).
Each of these products will need to differentiate itself to demonstrate clinical attractiveness. Datamonitor Healthcare analysts note that in terms of direct differentiation from other pipeline agents, ixekizumab targets the IL-17 ligand whereas brodalumab targets the IL-17 receptor, which could potentially result in differential effects between these two agents, with a profile favoring ixekizumab.
Ixekizumab uncovered
In Lilly's three UNCOVER studies, patients received either placebo or 80mg of ixekizumab every two or four weeks for 12 weeks, following a 160mg starting dose. UNCOVER-2 and -3 were active comparator studies that also included arms in which patients received etanercept 50mg twice weekly for 12 weeks.
Between 78% and 90% of ixekizumab patients with both dose regimens achieved at least a 75% reduction in PASI score (PASI 75) at 12 weeks. Of these, 31% to 41% achieved PASI 100, or clear skin, at week 12. For comparison, between 5% and 7% of patients treated with etanercept in the UNCOVER-2 and -3 studies achieved PASI 100, Lilly said.
Significant improvements in skin clearance measures for ixekizumab patients were seen in the first week when compared to either placebo or etanercept, and continued through week 12.
Patients treated with both dosing regimens of ixekizumab had significantly greater levels of skin clearance compared with both placebo and etanercept at 12 weeks, measured by the PASI index and the Static Physician Global Assessment (sPGA).
The most frequently reported events (more than 5% across all three studies) were nasopharyngitis and injection site reactions, most of which were mild.