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## Diabetes 

With the approval of Forxiga  (dapagliflozin) in the EU and the company’s acquisition of Amylin Pharmaceuticals, both in 2012, Bristol-Myers Squibb solidly enhanced the breadth of our product portfolio and the possibilities for addressing unmet medical need in diabetes treatment. 

And by focusing on the cardiovascular co-morbidities that patients with type 2 diabetes often encounter, including obesity and hypertension, we have contin- ued to expand our efforts beyond glycemic control to cardiovascular protection. 

The result: through our Diabetes Alliance with AstraZeneca, we are offering physicians more options for making the right choices for individual patients. 

“What resonates best with physicians is to talk about treatment objectives, based on the patient’s characteristics, including their behavior,” says Patrick Loustau, senior vice president, Global Commercialization, Cardiovascular and Metabolics. “We believe our major treatments can fit well into different types of treatment objectives.” 

Chris Cann, disease area lead for Metabolics, explains: “After you’re diagnosed, you have to control your blood sugar, adhere to a much stricter diet, and have better treatment for hypertension and other cardiovascular conditions and risk factors. It often becomes challenging for a patient with diabetes to manage these multiple co-morbidities. Having a range of options gives the physician and patient more choices at any particular time in a patient’s disease.” 

Forxiga  is the first in a new class of drugs called SGLT2 inhibitors. It harnesses the kidneys to help reduce blood sugar by excreting excess sugar into the urine, 

thus lowering hemoglobin A1c levels while also providing reductions in weight and blood pressure. Discussions with the U.S. Food and Drug Administra- tion (FDA) have created a likely path forward for the company to resubmit an updated Forxiga  filing for consideration in the U.S. by the summer of 2013. 

The Amylin acquisition added Byetta  (exenatide), a twice-daily injectable, and its once-weekly formulation, Bydureon  (exenatide extended-release for inject- able suspension). Both mimic the activity of a human hormone, glucagon-like peptide (GLP-1), which stimulates insulin secretion from the pancreas, but only when blood sugar is high. Doing so effectively regulates glucose metabolism while better controlling the blood sugar spikes that occur right after eating, and slows the emptying of the stomach, which can contribute to weight loss. 

Byetta , launched in 2005, was the first GLP-1 agonist. When Bydureon was approved in January 2012, it became the first and only weekly type 2 diabetes medication available. We plan to enhance the ease and convenience of Bydureon  administration and, over time, to transform the medicine into a once-monthly treatment. Symlin  (pramlintide), a third therapy developed at Amylin, is a first-in-class therapy for patients with type 1 and type 2 diabetes whose blood sugar is not properly controlled with mealtime insulin therapy. 

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## A Unique Technology for a Novel Medicine 

Company researchers had to create innovative technological solutions to produce Bydureon , a novel, sustained- release, once-weekly formulation of a twice-daily injectable for type 2 diabetes. 

“We take the active ingredient – exena - tide – and formulate it with a polymer into what are biodegradable micro - spheres, a unique technology where the microspheres are slowly absorbed, providing a controlled release of the active drug over seven days,” explains Bob MacKay, general manager of the facility where Bydureon  is produced. “The challenge was to make the micro - spheres of the appropriate size to give you the product release profile you wanted – and to create a polymer with the right composition.” 

Another challenge was to build the right manufacturing plant, one that could produce the microspheres with the desired qualities – including ensuring a sterile product – and in the quantities required. Located on 44 acres in West Chester, Ohio, north of Cincinnati, the highly automated plant was completed in 2009 at a cost of about $800 million. It became operational in late 2010 and currently has 330 full-time employees, representing key disciplines, including chemical and automation engineering, microbiology and chemistry. r 

