Abbott Reports Psoriasis Phase III Results of its Investigational IL-12/23 Inhibitor Briakinumab (ABT-874)

Data Compares Briakinumab (ABT-874) to Etanercept, Methotrexate and Placebo in Psoriasis

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Oct 11, 2010, 10:00 ET

ABBOTT PARK, Ill., Oct. 11 /PRNewswire-FirstCall/ -- In four separate pivotal clinical studies presented on Friday, a greater percentage of moderate to severe chronic plaque psoriasis patients treated with briakinumab, Abbott's investigational IL-12/23 inhibitor (ABT-874), achieved 75 percent or better skin clearance rates than those treated with etanercept (Enbrel®), methotrexate or placebo. Abbott (NYSE: ABT) presented data from all briakinumab pivotal studies in psoriasis at the European Association of Dermatology and Venereology scientific sessions.

Briakinumab is an investigational biologic medication that targets IL-12/23 proteins linked to inflammation. Briakinumab is the second medication in the IL-12/23 class to have completed Phase III trials for the treatment of plaque psoriasis. The most commonly prescribed biologics used to treat moderate to severe chronic plaque psoriasis target a protein called tumor necrosis factor (TNF).

"While anti-TNFs are the cornerstone of biologic treatment for psoriasis, these data suggest that briakinumab may be evaluated as a potentially important alternative treatment option for some psoriasis patients," said Eugene Sun, M.D., vice president, Global Pharmaceutical Development, Abbott.

In the largest of the four studies, a 52-week study comparing briakinumab (N=981) to placebo (N=484), significantly more patients experienced skin clearance versus patients with placebo. At week 12, skin clearance of 75 percent (PASI 75) was achieved in 80.7 percent of patients receiving briakinumab every four weeks versus 4.5 percent with placebo. Skin clearance of 90 percent (PASI 90) was achieved in 61.6 percent on briakinumab versus 1.4 percent on placebo, and 100 percent skin clearance (PASI 100), was achieved in 32.2 percent of patients versus no placebo patients. Of the 290 briakinumab patients that achieved PASI 75 and Physician's Global Assessment (PGA) of clear or normal at week 12, 82.4 percent maintained PASI 75 at week 52, versus 9.0 percent of the 144 patients on placebo.

Of the 243 briakinumab patients that achieved PASI 90 and PGA of clear or normal at week 12, 81.5 percent maintained PASI 90 at week 52, versus 9.2 percent of the 109 placebo patients. Of the 298 briakinumab patients who achieved PGA of clear or normal at week 12, 63.4 percent of patients demonstrated PASI 100 at week 52, versus 4 percent of the 149 placebo patients.

The most common adverse events observed across all four briakinumab pivotal studies and the ongoing open-label extension were upper respiratory infection, nasopharyngitis (stuffy nose), headache, arthralgia (joint pain), hypertension and back pain. The incidences of infection and malignancy with briakinumab were generally higher than those with placebo, but were similar to those in patients treated with etanercept or methotrexate. Because briakinumab is a modulator of the immune system, these results are not unexpected and emphasize the need for close monitoring and surveillance. Major adverse cardiovascular events (MACE) including myocardial infarction, stroke and cardiovascular death were observed in one of the four briakinumab pivotal studies and in the ongoing open-label extension. An analysis of the data showed that all patients experiencing MACE in the pivotal briakinumab study had identifiable underlying cardiovascular risk factors.

"These clinical trials advance our understanding of the benefits and risks of inhibiting IL-12/23 proteins with briakinumab in patients with psoriasis," said Kenneth Gordon, M.D., Head, Division of Dermatology, NorthShore University Health System.

About the Briakinumab Clinical Program

The following pivotal studies were presented at the European Association of Dermatology and Venereology scientific sessions in Gothenburg, Sweden, Oct. 6-10, 2010:

M10-255 Study

Phase III, 52-week, double-blind, randomized, multi-center, active controlled study of 317 patients with moderate to severe psoriasis comparing briakinumab to methotrexate treatment
Primary endpoints were based on PASI (Psoriasis Area and Severity Index) and PGA measures
At baseline (week 0), patients were randomized to receive briakinumab or methotrexate (MTX). The briakinumab treatment group received 200 mg at weeks 0 and 4 and 100 mg every 4 weeks from weeks 8 to 48. The MTX treatment group received MTX (5 to 25 mg weekly from weeks 0 to 51) plus oral folate (5 mg weekly from weeks 0 to 51)
Patients in the MTX group received MTX 5 mg at week 0, 10 mg at week 1, and 15 mg/wk from weeks 2 to 9. At weeks 10 and 16, MTX dosage was increased by 5 mg (to 20 mg/wk at week 10 and 25 mg/wk at week 16) for patients who did not achieve PASI >/- 75 or a PGA of 0 or 1 (indicating clear skin or minimal psoriasis plaques)
The four primary endpoints were percentage of patients with PASI 75 at week 24, PGA of 0 or 1 at week 24, PASI 75 at week 52 and PGA score of 0 or 1 at week 52
At 24 weeks, 81.8 percent of briakinumab patients achieved PASI 75 clearance compared with 39.9 percent of those taking methotrexate. PASI 90 clearance was achieved by 63.6 percent of briakinumab patients versus 22.7 percent with methotrexate, while PASI 100 was achieved by 42.2 percent of briakinumab patients versus 8.6 percent of methotrexate patients
At 52 weeks, 66.2 percent of briakinumab patients achieved PASI 75 clearance compared with 23.9 percent of methotrexate patients. PASI 90 clearance was achieved by 59.7 percent of briakinumab patients versus 17.8 percent of those taking methotrexate, while PASI 100 was achieved by 45.5 percent of briakinumab patients versus 9.2 percent of methotrexate patients
Results on the primary endpoints were statistically significant - P<0.001, briakinumab versus methotrexate
The most common adverse events in briakinumab and methotrexate treatment groups were nasopharyngitis, headache, diarrhea, arthralgia and upper respiratory tract infection
Three cases of malignancies were reported in the briakinumab group
Serious infections were reported by four (2.6 percent) patients in the briakinumab group and three (1.8 percent) patients in the MTX group
No MACE were reported for either treatment group

M06-890

Phase III, 52-week, randomized, multi-center study of 1,465 patients comparing the efficacy and safety of two dosing regimens of briakinumab to placebo
In an induction phase, patients were first randomized in a 2:1 ratio at week 0 to receive briakinumab 200 mg at weeks 0 and 4, followed by 100 mg at week 8 (n=981), or placebo injections to match briakinumab (n=484)
Randomization of those patients who had a clinical response (PGA 0 or 1) occurred at week 12, with patients receiving briakinumab 100 mg every four weeks (n=298), briakinumab 100 mg every 12 weeks (n=298) or placebo injections to match briakinumab (n=149)
Co-primary endpoints were proportion of patients achieving PGA 0 or 1 at week 12; proportion of patients achieving PASI 75 at week 12; and proportion of patients achieving PGA 0 or 1 at week 52
Briakinumab was statistically superior to placebo by the primary endpoint measures at week 12: 76 percent of patients achieved PGA 0 or 1 at week 12 compared to 4.3 percent with placebo and 80.7 percent achieved PASI 75 at week 12 compared to 4.5 percent with placebo
At 52 weeks, 79.2 percent of patients treated every four weeks with briakinumab achieved PGA 0 or 1 compared to 41.6 percent treated every 12 weeks with briakinumab and 6 percent treated with placebo
Results on the primary endpoints were statistically significant - P<0.001, briakinumab versus placebo
A higher incidence of infection and skin malignancy adverse events were observed in briakinumab versus placebo-treated patients
Seven cases of major adverse cardiovascular events were reported in the briakinumab group compared with no events in the placebo group during the 12-week randomized phase

M10-114 Study

Phase III, 12-week, double-blind, double-dummy, randomized multi-center study in 347 patients with moderate to severe psoriasis comparing the efficacy and safety of treatment with briakinumab (n=138) to etanercept (n=141) and placebo (n=68)
Patients were randomized to receive briakinumab 200 mg at weeks 0 and 4, then 100 mg at week 8; etanercept 50 mg twice weekly; or placebo injection to match briakinumab and etanercept
There were two co-primary endpoints at week 12 – proportion of patients achieving PGA 0 or 1 and proportion of patients achieving PASI 75
Briakinumab was statistically superior to both etanercept and placebo on both primary endpoint measures, with 71 percent of briakinumab-treated patients achieving PGA 0 or 1 (39.7 percent with etanercept, 2.9 percent with placebo) and 81.9 percent of briakinumab-treated patients achieving PASI 75 (56 percent with etanercept, 7.4 percent with placebo)
Results on the primary endpoints were statistically significant - P<0.001, briakinumab versus etanercept and P<0.001, briakinumab versus placebo
A slightly higher percentage of patients receiving etanercept or briakinumab experienced adverse events as compared with patients receiving placebo, however the safety profile for the two active treatments was similar
No differences were seen across the active treatment groups for the percentage of patients experiencing serious infections or malignancies
No MACE were reported in any treatment group

M10-315 Study

Phase III, 12-week, double-blind, double-dummy, randomized multi-center study in 350 patients with moderate to severe psoriasis comparing the efficacy and safety of treatment with briakinumab (n=139) to etanercept (n=139) and placebo (n=72)
Patients were randomized to receive briakinumab 200 mg at weeks 0 and 4, then 100 mg at week 8; etanercept 50 mg twice weekly; or placebo injection to match briakinumab and etanercept
There were two co-primary endpoints at week 12 – proportion of patients achieving PGA 0 or 1 and proportion of patients achieving PASI 75
Briakinumab was superior to both etanercept and placebo on both primary endpoint measures, with 72.7 percent of briakinumab-treated patients achieving PGA 0 or 1 (29.5 percent with etanercept, 4.2 percent with placebo) and 80.6 percent of briakinumab-treated patients achieving PASI 75 (39.6 percent with etanercept and 6.9 percent with placebo)
Results on the primary endpoints were statistically significant - P<0.001, briakinumab versus etanercept and P<0.001, briakinumab versus placebo
A higher percentage of patients in the briakinumab and entanercept treatment groups experienced adverse events than patients in the placebo group (50.4 percent, 49.6 percent, and 44.4 percent, respectively)
The frequently reported adverse events occurring in at least 5 percent of patients in both the briakinumab and etanercept treatment groups were upper respiratory tract infection (7.2 percent and 11.5 percent, respectively) and nasopharyngitis (7.2 percent and 7.9 percent, respectively)
Eight patients experienced malignancies: three cases in the briakinumab treatment group, four cases in the etanercept treatment group, and one case in the placebo group
No cases of serious infection were reported in any of the groups
No MACE were reported in any treatment group

About Abbott

Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs nearly 90,000 people and markets its products in more than 130 countries.

Abbott's news release and other information are available on the company's Web site at www.abbott.com

SOURCE Abbott