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Amgen And AstraZeneca Announce Positive Results From Third And Final Pivotal Phase 3 Study Of Brodalumab In Patients With Moderate-To-Severe Plaque Psoriasis
Results showed that 44.4 percent of patients in the brodalumab 210 mg group, 33.6 percent of patients in the brodalumab weight-based group, 25.7 percent of patients in the brodalumab 140 mg group, 21.7 percent of patients in the Stelara group and 0.6 percent of patients in the placebo group achieved total clearance of skin disease (PASI 100). In addition, 86.3 percent of patients in the brodalumab 210 mg group, 77.0 percent of patients in the brodalumab weight-based group, 66.6 percent of patients in the brodalumab 140 mg group, 70.0 percent of patients in the Stelara group and 8.1 percent of patients in the placebo group achieved PASI 75.
"Results from AMAGINE-2 underscore that treatment with brodalumab could help a significant number of moderate-to-severe plaque psoriasis patients achieve total clearance of their skin disease, and the great majority achieve at least a 75 percent improvement in their disease," said
All key secondary endpoints comparing brodalumab with placebo were met. The first key secondary endpoint comparing PASI 100 for brodalumab (140 mg) with Stelara at week 12 was numerically greater but not statistically significant (p=0.078). The remaining secondary endpoints against Stelara were also numerically greater (all nominal p-values were less than 0.05), but could not be deemed statistically significant due to the sequential testing method.
The most common adverse events that occurred in the brodalumab groups (more than 5 percent of patients in either group) were common cold, upper respiratory tract infection, headache and joint pain. Serious adverse events occurred in 1.0 percent of patients in the 210 mg group, 1.2 percent of patients in the weight-based group, and 2.1 percent of patients in the 140 mg group compared with 1.3 percent for Stelara and 2.6 percent for placebo during the placebo-controlled period. There was one (0.2 percent) fatal event of stroke in the brodalumab 210 mg group during the 12-week placebo-controlled induction phase, deemed by the study investigator as unrelated to treatment.
Brodalumab is the only investigational treatment in development that binds to the interleukin-17 (IL-17) receptor and inhibits inflammatory signaling by blocking the binding of several IL-17 cytokines (A, F and A/F) to the receptor. The IL-17 receptor and cytokine family play a central role in development and clinical manifestations of plaque psoriasis.
"These results confirm our belief that targeting the IL-17 receptor to inhibit inflammatory signaling can have significant benefit for psoriasis patients," said
The AMAGINE program is comprised of three pivotal Phase 3 studies designed to assess the efficacy and safety of brodalumab in patients with moderate-to-severe plaque psoriasis. Top-line results from AMAGINE-1TM, comparing brodalumab with placebo, were released in
AMAGINE-2 Study Design
AMAGINE-2 is a Phase 3 study that assessed the safety and efficacy of brodalumab given at two doses every two weeks via subcutaneous injection compared with Stelara and placebo in patients with moderate-to-severe plaque psoriasis. The study also assessed the safety and efficacy of four maintenance regimens of brodalumab. The primary endpoint comparing 210 mg of brodalumab as well as a pre-specified weight-based analysis group with Stelara was the proportion of patients achieving total clearance of skin disease, as measured by PASI 100 at week 12. When comparing brodalumab with placebo, the primary endpoints included the proportion of patients achieving at least a 75 percent improvement from baseline in disease severity (PASI 75) at week 12, and the achievement of clear or almost clear skin, according to the sPGA (0 or 1) at week 12.
The study began with a 12-week, double-blind, active comparator- and placebo-controlled induction phase, where patients were randomized in a 2:2:1:1 ratio to receive brodalumab (210 mg or 140 mg), Stelara (per the labeled dose), or placebo. At week 12, patients originally randomized to either brodalumab arm were re-randomized 2:2:2:1 into the maintenance phase to receive brodalumab 210 mg or 140 mg at four different maintenance regimens. Patients originally randomized to Stelara continued to receive the same treatment, and those originally randomized to receive placebo began 210 mg of brodalumab every two weeks.
At week 52, patients entered the long-term extension portion of the study, and those who were originally randomized to receive Stelara began receiving 210 mg of brodalumab every two weeks. All other patients continued on treatment with brodalumab at the same dose they were being treated with at week 52. Patients may be enrolled in the study for up to 271 weeks (approximately five years).
A PASI score is a measure of psoriatic plaque redness, scaling and thickness and the extent of involvement in each region of the body. Treatment efficacy is often measured by the reduction of PASI from baseline (e.g., a 75 percent reduction is known as PASI 75, a 90 percent reduction is known as PASI 90 and PASI 100 is total clearance of skin disease).
sPGA is a physician's rating of psoriasis severity at a given point in time based on plaque, scaling and redness. A physician can rate a patient's psoriasis as clear (0), almost clear (1), mild (2), moderate (3), severe (4), or very severe (5).
Psoriasis is a serious, chronic inflammatory disease that causes raised, red, scaly patches to appear on the skin, typically affecting the outside of the elbows, knees or scalp, though it can appear on any location.1,2 Approximately 125 million people worldwide have psoriasis and 80 percent of those patients have plaque psoriasis.3,4
About Brodalumab (AMG 827)
Brodalumab is a novel human monoclonal antibody that binds to the interleukin-17 (IL-17) receptor and inhibits inflammatory signaling by blocking the binding of several IL-17 ligands to the receptor. By stopping IL-17 ligands from activating the receptor, brodalumab prevents the body from receiving signals that may lead to inflammation. The IL-17 pathway plays a central role in inducing and promoting inflammatory disease processes.5 In addition to moderate-to-severe plaque psoriasis (Phase 3), brodalumab is currently being investigated for the treatment of psoriatic arthritis (Phase 3) and asthma (Phase 2).
This news release contains forward-looking statements that are based on the current expectations and beliefs of
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Karl Hård, +44 20 7604 8123, mob: +44 7789 654364
National Psoriasis Foundation. Symptoms and diagnosis. http://www.psoriasis.org/about-psoriasis/symptoms-and-diagnosis. Accessed on September 10, 2014. National Psoriasis Foundation. Frequently Asked Questions. http://www.psoriasis.org/about-psoriasis/faqs. Last updated 2014. Accessed on September 10, 2014. International Federation of Psoriasis Associations. Psoriasis is a Serious Disease Deserving Global Attention: A report by the International Federation of Psoriasis Associations. www.ifpa-pso.org/getfile.ashx?cid=279366&cc=3&refid=18. Accessed on September 10, 2014. American Academy of Dermatology. Psoriasis. http://www.aad.org/media-resources/stats-and-facts/conditions/psoriasis. Last updated 2014. Accessed on September 10, 2014.
- Miossec P, Korn T, Kuchroo VK. Interleukin-17 and Type 17 Helper T Cells.
The New England Journal of Medicine. 2009; 361: 888-98.
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