Lilly's ixekizumab Phase II trial on plaque psoriasis meets primary endpoint

New Phase II data, published today in the New England Journal of Medicine, showed that Eli Lilly and Company's (NYSE: LLY) ixekizumab (pronounced ix" e kiz' ue mab, previously known as LY2439821), an anti-IL-17 monoclonal antibody, met its primary endpoint in patients with moderate-to-severe plaque psoriasis, with significantly more patients achieving at least a 75 percent improvement in Psoriasis Area and Severity Index (PASI) scores from baseline (PASI 75) compared with placebo at week 12.

PASI score represents a combined assessment of overall skin lesions ranging from 0 for no psoriasis to 72 for the worst possible psoriasis in a patient and is a standard measure of skin disease severity in clinical trials in psoriasis. A PASI 75 response in a patient represents a 75 percent reduction of PASI scores from baseline.  

In the 142-subject study, significantly more patients achieved a PASI 75 response in the 150 mg (82 percent), 75 mg (83 percent) and 25 mg (77 percent) ixekizumab groups compared with placebo (8 percent, p<0.001) at week 12. The 10 mg dose (29 percent) did not separate from placebo at week 12.

Secondary endpoints included an evaluation of the percentage of patients achieving at least 90 percent and 100 percent improvement in PASI (PASI 90 or PASI 100) at week 12. In patients treated with ixekizumab, the percentages of patients achieving a PASI 90 response were 71 percent (150 mg), 59 percent (75 mg) and 50 percent (25 mg), which were significantly higher than with placebo (0 percent). PASI 100 responses were significantly better at the 150 mg dose (39 percent) and 75 mg dose (38 percent) when compared with placebo (0 percent). PASI 100 responses at the 25 mg (17 percent) and 10 mg doses (0 percent) were not significantly greater than placebo, nor was the PASI 90 response at the 10 mg dose (18 percent).

PASI 75 response was significantly better than placebo as early as week 2 at the highest dose, and significant differences from placebo in PASI scores were seen as early as week 1 at the two highest doses and by week 4 for the remaining two doses. Differences from placebo were sustained to week 20 in both PASI 75 responses and PASI scores.

Skin disease severity also was evaluated by static Physician Global Assessments (sPGA), with patients having a score of 3-5 (moderate to severe disease) at baseline. Significantly more patients treated with ixekizumab achieved an sPGA score of 0 (clear of disease) or 1 (minimal disease), when compared with placebo at week 12. The percentage of patients achieving an sPGA 0 or 1 score were 71 percent (150 mg), 72 percent (75 mg), 70 percent (25 mg) and 25 percent (10 mg) compared with 8 percent (placebo), with the highest three doses being significantly higher than placebo. The percentage of patients achieving an sPGA score of 0 at week 12 were 46 percent (150 mg), 38 percent (75 mg), 20 percent (25 mg), 7 percent (10 mg) and 0 percent (placebo), again with the highest three ixekizumab doses being significantly higher than placebo.

Approximately 40 percent of patients in the two highest dose groups had complete clearance of psoriasis plaques on the skin, as reflected by a reduction in the PASI score by 100 percent or an sPGA score of 0 at 12 weeks.

In addition, significant reductions in mean Nail Psoriasis Severity Index (NAPSI) and Psoriasis Scalp Severity Index (PSSI), which evaluate disease in the difficult-to-treat areas of nails and scalp, respectively, were seen at the two highest ixekizumab doses compared with placebo at week 12 (NAPSI: 150 mg [-49.3 percent], 75 mg  [-57.1 percent], placebo [+6.8 percent]; PSSI: 150 mg [-84.8 percent], 75 mg [-94.8 percent], placebo [-30.5 percent]).

The frequency of adverse events in both the combined ixekizumab groups and in the placebo group was 63 percent, with the most common adverse events observed being nasopharyngitis (inflammation of the nasal passages and of the upper part of the pharynx), upper respiratory infection, injection site reactions and headache. There were no serious adverse events reported. Infections occurred in 33 percent (38 patients) of subjects receiving ixekizumab and 26 percent (seven patients) receiving placebo. No dose-related trends in infections or other adverse events were observed. Four patients (one in the placebo group, two in the 10 mg group and one in 25 mg group) discontinued the study due to adverse events.

"These data suggest ixekizumab may be an effective treatment for patients with chronic moderate-to-severe plaque psoriasis and could represent a new treatment approach for patients with this condition," said Craig Leonardi, M.D., clinical professor of dermatology at the Saint Louis University School of Medicine, and lead author of the manuscript. "Further studies are needed, but we are encouraged by the results showing improvements in skin clearance early in treatment."

Psoriasis is the most prevalent chronic, autoimmune disease of the skin in the United States, affecting about 7.5 million people. It occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells. Approximately 17 percent of psoriasis patients have moderate-to-severe plaque psoriasis.

"While there are a number of commonly used treatments for autoimmune diseases, new and alternative treatment options are needed for those impacted by these potentially debilitating conditions, including psoriasis," said Eiry Roberts, M.D., vice president of autoimmune product development at Lilly. "We are committed to developing new autoimmune therapies such as ixekizumab, which was discovered in our own research labs and is now being studied in Phase III for psoriasis."