Lilly and Novartis reveal separate studies on plaque psoriasis

Good news for patients with moderate-to-severe plaque psoriasis. In only two days two big pharmaceutical companies have issued press releases about their studies in treatmenet of this desease. On March 4, Eli Lilly has issued press release about its study on this desease. The press release follows.

Eli Lilly and Company have announced  that treatment for moderate-to-severe plaque psoriasis with ixekizumab resulted in clinically meaningful improvements as early as one week, compared to patients treated with etanercept or placebo. Detailed results of this combined analysis of UNCOVER-2 and UNCOVER-3 were presented during the American Academy of Dermatology (AAD) Annual Meeting taking place March 4-8 in Washington, D.C.

Lilly says that UNCOVER-2 and UNCOVER-3 are double-blind, multicenter, Phase 3 studies evaluating more than 2,500 patients with moderate-to-severe plaque psoriasis across 19 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.

This combined analysis evaluated the speed of onset of clinical improvement as measured by mean percentage improvement in Psoriasis Area Severity Index (PASI) score from baseline, as well as time to PASI 50 and PASI 75 among patients treated with ixekizumab, etanercept or placebo. PASI measures the extent and severity of psoriasis by assessing average redness, thickness and scaliness of skin lesions (each graded on a zero to four scale), weighted by the body surface area of involved skin.[1]

“Studies have shown that clinical improvement observed early during psoriasis treatment can help predict clinical response at later times”, said Craig Leonardi, M.D., lead study author and clinical professor of dermatology at St. Louis University School of Medicine. “In this analysis of ixekizumab, early results were seen in patients with moderate-to-severe plaque psoriasis, an extensive and difficult-to-treat disease. According to patients and their dermatologists, rapid clearing of psoriasis plaques is one of the most important attributes for treatment success.”

According to Lilly significant differences in mean percentage improvement of psoriasis plaques were observed among patients treated with ixekizumab compared to etanercept and placebo:

At one week, the mean percentage improvement was 32.7 percent in the group randomized to receive ixekizumab every two weeks, 10.3 percent in etanercept and 5.31 percent in placebo (p < 0.001 for all comparisons).
At two weeks, the mean percentage improvement was 53.6 percent in the group randomized to receive ixekizumab every two weeks, 23.3 percent in etanercept and 9.25 etanercept in placebo (p < 0.001 for all comparisons).
Treatment with ixekizumab also resulted in clinically meaningful improvements (PASI 50) as early as one week, which were statistically significantly different compared with etanercept and placebo.

At one week, PASI 50 was achieved by 22.8 percent of patients treated with ixekizumab every two weeks compared to 3.9 percent among those treated with etanercept and 1.4 percent in placebo (p < 0.001 for all comparisons).
At two weeks, PASI 50 was achieved among 58.8 percent of patients treated with ixekizumab every two weeks compared to 14.6 percent of those treated with etanercept and 4.2 percent in placebo (p < 0.001 for all comparisons).
Median time to PASI 75 was 30 days among patients treated with ixekizumab every two weeks and 85 days among those treated with etanercept.

The majority of treatment-emergent adverse events were mild or moderate. The most frequently reported adverse drug reactions were injection site reactions and upper respiratory tract infections (most frequently nasopharyngitis) and generally did not lead to treatment discontinuations. Overall, the safety profile was comparable to etanercept in these two clinical studies.

Ixekizumab is the company’s investigational medicine for the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis.

Lilly About Ixekizumab
Ixekizumab is an IgG4 monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of pro-inflammatory cytokines and chemokines.

Just day later, Novartis issued  press release about its own study:

Novartis has announced new late-breaking data from the head-to-head CLEAR study, demonstrating that Cosentyx (secukinumab) remains superior to Stelara (ustekinumab) in achieving sustained skin clearance (PASI 90 response) at 52 weeks for adults living with moderate-to-severe psoriasis. These findings were presented for the first time at the American Academy of Dermatology (AAD) Annual Meeting in Washington, DC.

In its press release Novartis said that Cosentyx is the first fully human interleukin-17A inhibitor approved for adults to treat moderate-to-severe plaque psoriasis, and was recently approved for the treatment of psoriatic arthritis and ankylosing spondylitis in the EU and US.

“Cosentyx continues to demonstrate superior and sustainable efficacy against currently available biologics and is a proven first-line treatment option for adult patients with moderate-to-severe psoriasis,” said Vasant Narasimhan, Global Head, Drug Development and Chief Medical Officer, Novartis. “Cosentyx has the potential to give more people with psoriasis than ever before the benefit of long-lasting skin clearance.”

The ultimate aim of psoriasis treatment is clear skin, and the Psoriasis Area Severity Index (PASI) 90 response is considered an important measure of treatment success. Meeting all primary and secondary endpoints at Weeks Four, 16 and 52, Cosentyx demonstrated it remains consistently superior to Stelara in achieving and sustaining PASI 90 response (76.2% vs. 60.6%; P<0.0001), and significantly better in achieving PASI 100 (clear skin) response (45.9% vs. 35.8%; P=0.0103) at 52 weeks. Cosentyx also showed significantly greater and sustained Dermatology Life Quality Index (DLQI) 0/1 responses versus Stelara (71.6% vs. 59.2%; P=0.0008).

According to Novartis, the study also demonstrated Cosentyx had a superior rapid onset of action compared to Stelara, with half of Cosentyx patients achieving PASI 75 as early as Week Four (50.0% vs. 20.6%, P<0.0001)[4]. Cosentyx had a similar safety profileto that of Stelara in the study, which was consistent with that reported in the pivotal Cosentyx Phase III studies.

Affecting around 125 million people globally, psoriasis is a chronic skin condition that causes itching, scaling and pain, and can have a significant impact on physical and psychological wellbeing. Despite this, up to half of patients receive no treatment, and of those who do, many (52%) remain dissatisfied with their disease management.

Novartis About the CLEAR study

CLEAR (Comparison to assess Long-term Efficacy, sAfety and toleRability of secukinumab vs. ustekinumab) is a multi-center, double-blind, parallel-group study of Cosentyx (n=334) versus Stelara (n=335) to compare efficacy, safety and tolerability in adults with moderate-to-severe plaque psoriasis. Patients were randomized to receive either Cosentyx (300 mg) by subcutaneous injection at Baseline, Weeks One, Two and Three, then every four weeks from Week Four, or Stelara (dosing per package label). Cosentyx achieved the primary objective of superior PASI 90 response at Week 16. These data were published as an e-publication in the Journal of the American Academy of Dermatology, June 17, 2015. The 52-week PASI 90 response is a secondary objective in this study. PASI 100 and DLQI responses at 52 weeks are exploratory endpoints.