Astrazeneca Regulatory News (AZN)

AMGEN AND ASTRAZENECA ANNOUNCE POSITIVE RESULTS FROM SECOND PIVOTAL PHASE III STUDY OF BRODALUMAB IN PATIENTS WITH MODERATE-TO-SEVERE PLAQUE PSORIASIS

Brodalumab meets all primary and all key secondary endpoints

Meets primary endpoint of superiority to Stelara® (ustekinumab) in achieving total skin clearance (PASI 100)

Meets co-primary endpoints against placebo

AstraZeneca and Amgen today announced that AMAGINE-3TM, a pivotal, multi-arm Phase III trial evaluating two doses of brodalumab in more than 1,800 patients with moderate-to-severe plaque psoriasis, met its primary endpoints when compared with both Stelara® (ustekinumab) and placebo at week 12. Brodalumab was shown to be superior to Stelara on the primary endpoint of achieving total clearance of skin disease, as measured by the Psoriasis Area Severity Index (PASI 100). When compared with placebo, a significantly greater proportion of patients treated with brodalumab achieved at least a 75 percent improvement from baseline in disease severity at week 12, as measured by the Psoriasis Area Severity Index (PASI 75). A significantly greater proportion of patients treated with brodalumab also achieved clear or almost clear skin at week 12 compared with placebo, according to the static Physician Global Assessment (sPGA 0 or 1). All key secondary endpoints comparing brodalumab with Stelara and placebo were also met.

Results showed that 36.7 percent of patients in the brodalumab 210 mg group, 27 percent of patients in the brodalumab 140 mg group, 18.5 percent of patients in the Stelara group and 0.3 percent of patients in the placebo group achieved total clearance of skin disease (PASI 100). In addition, 85.1 percent of patients in the brodalumab 210 mg group, 69.2 percent of patients in the brodalumab 140 mg group, 69.3 percent of patients in the Stelara group and 6 percent of patients in the placebo group achieved PASI 75.

"Despite a variety of treatment options available for psoriasis, many patients still do not meet skin clearance goals," said Sean E. Harper, Executive Vice President of Research and Development at Amgen. "These results are of particular importance as they are the first to demonstrate superiority to Stelara in achieving total skin clearance, and the second positive pivotal Phase III study evaluating brodalumab in patients with moderate-to-severe plaque psoriasis."

The most common adverse events that occurred in the brodalumab arms (more than 5 percent of patients in either group) were common cold, joint pain, upper respiratory tract infection and headache. Serious adverse events occurred in 1.4 percent of patients in the 210 mg group and 1.6 percent of patients in the 140 mg group compared with 0.6 percent for Stelara and 1 percent for placebo during the placebo-controlled period.

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, A/F and C) to the receptor. The IL-17 receptor and cytokine family play a central role in development and clinical manifestation of plaque psoriasis.

"These results add to the growing body of evidence supporting the potential value that brodalumab may bring to the treatment of psoriasis by targeting the IL-17 receptor," said Briggs Morrison, Executive Vice President, Global Medicines Development and Chief Medical Officer, AstraZeneca. "We look forward to sharing results later this year from AMAGINE-2TM, our remaining head-to-head study evaluating brodalumab versus Stelara."

The AMAGINE programme is composed of three Phase III studies designed to assess the efficacy and safety of brodalumab in patients with moderate-to-severe plaque psoriasis. Top-line results from AMAGINE-1TM, designed to assess the efficacy and safety of brodalumab compared with placebo, were released in May 2014. Detailed results from the AMAGINE-3 study will be submitted to the appropriate scientific forum for presentation and/or publication. Results from AMAGINE-2 are expected by year end.

About AMAGINE-3 Study Design

AMAGINE-3 is a Phase III study that assessed the safety and efficacy of brodalumab given at two doses every two weeks via subcutaneous injection compared with placebo and Stelara 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 brodalumab 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 randomised 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 randomised to either brodalumab arm were re-randomised 2:2:2:1 into the maintenance phase to receive brodalumab 210 mg or 140 mg at four different maintenance regimens. Patients originally randomised to Stelara continued to receive the same treatment, and those originally randomised 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 randomised 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).

About Psoriasis

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. Approximately 125 million people worldwide have psoriasis and 80 percent of those patients have plaque psoriasis.

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. In addition to moderate-to-severe plaque psoriasis (Phase III), brodalumab is currently being investigated for the treatment of psoriatic arthritis (Phase III) and asthma (Phase II).

About the Amgen and AstraZeneca Collaboration

In April 2012, Amgen and AstraZeneca formed a collaboration to jointly develop and commercialize five monoclonal antibodies from Amgen's clinical inflammation portfolio. With oversight from joint governing bodies, Amgen leads clinical development and commercialisation for brodalumab (Phase III for moderate-to-severe plaque psoriasis and psoriatic arthritis, Phase II for asthma) and AMG 557/MEDI5872 (Phase Ib for autoimmune diseases, such as systemic lupus erythematosus). AstraZeneca, through its biologics arm MedImmune, leads clinical development and commercialisation for MEDI7183/AMG 181 (Phase II for ulcerative colitis and Crohn's disease), MEDI2070/AMG 139 (Phase II for Crohn's disease) and MEDI9929/AMG 157 (Phase II for asthma).

About Amgen

Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be the world's largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com.

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12 November 2014

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