Amgen Inc. and AstraZeneca PLC Announce Positive Results from Third and Final Pivotal Phase 3 Study of Brodalumab in Patients with Moderate-To-Severe Plaque Psoriasis
Nov 25 14
Amgen and AstraZeneca announced that AMAGINE-2(TM), a pivotal, multi-arm Phase 3 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(R) (ustekinumab) and placebo at week 12. Brodalumab 210 mg given every two weeks and the brodalumab weight-based analysis group were each 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% 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). Results showed that 44.4% of patients in the brodalumab 210 mg group, 33.6% of patients in the brodalumab weight-based group, 25.7% of patients in the brodalumab 140 mg group, 21.7% of patients in the Stelara group and 0.6% of patients in the placebo group achieved total clearance of skin disease (PASI 100). In addition, 86.3% of patients in the brodalumab 210 mg group, 77.0% of patients in the brodalumab weight-based group, 66.6% of patients in the brodalumab 140 mg group, 70.0% of patients in the Stelara group and 8.1% of patients in the placebo group achieved PASI 75. 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% of patients in either group) were common cold, upper respiratory tract infection, headache and joint pain. Serious adverse events occurred in 1.0% of patients in the 210 mg group, 1.2% of patients in the weight-based group, and 2.1% of patients in the 140 mg group compared with 1.3% for Stelara and 2.6% for placebo during the placebo-controlled period. There was one (0.2%) 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. 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% 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). Amgen will continue to collect efficacy and safety data during this long-term exposure period.
Amgen Expects to Roll Out its Products for Treating Osteoporosis and Bone Cancers from its New Plant in Tuas by the End of 2016
Nov 21 14
Amgen expects to roll out its products for treating osteoporosis and bone cancers from its new plant in Tuas by the end of 2016. The SGD 200 million plant in Tuas Biomedical Park is the first next-generation biomanufacturing facility in the world. A model of efficiency, it is cheaper to build and run than conventional facilities; it took only a quarter of the capital cost to construct, and will need only a third of the operating expenses of a conventional facility. And 15 months was all it took for it to be built - half the time it takes to build a traditional plant. Despite this, it will still be able to churn out about a tonne of products annually, the same output as that of a conventional facility. The flexible, modular design means that the 120,000 square foot plant can be replicated in future locations; production capabilities can also be ramped up to accommodate the production of future cell-culture products. On top of this, the plant will run with more than 75% reduction in the usage of energy and water and in carbon dioxide emissions; solid waste generated and chemical usage will also be lower, which dovetails with Singapore's commitment to sustainable and innovative economic development. Amgen disclosed its plans for a second synthetic-molecule plant, to be ready in about three years. This plant will be near the first one and will produce the active pharmaceutical ingredient for a drug that treats multiple myeloma.
Amgen Completes Construction of its First Next-Generation Biomanufacturing Facility Located in Singapore
Nov 20 14
Amgen has completed construction of its first Next-Generation Biomanufacturing facility, located in Singapore, heralding a new stage of efficient and innovative production of medicines that treat serious diseases. Biologic medicines are produced in living cells and the new Tuas facility encompasses multiple technologies to enable greater speed, productivity and flexibility in commercial-scale manufacturing. Built in less than two years, the Next-Generation Biomanufacturing facility was completed in half the time required for conventional biomanufacturing plants. It uses single-use bioreactors, disposable plastic containers, continuous purification processing and real-time quality analysis. This flexible, modular design can be replicated in future facilities, enabling higher production and greater accessibility to patients around the world. The Next-Generation Biomanufacturing facility is expected to have the same annual output as a conventional facility but in a single building that will use less energy and water and have lower solid waste and emission levels - all in line with Singapore's commitment to sustainable and innovative economic development. Amgen also announced it will continue building at its Tuas site in Singapore and will soon open another facility where it will make carfilzomib, the active ingredient for Kyprolis(R).