The FDA is not bound by the advisory committee’s recommendation but takes its advice into consideration when reviewing the application for an investigational agent. The Prescription Drug User Fee Act (PDUFA) goal date for dapagliflozin is January 11, 2014.

Dapagliflozin is being reviewed by the FDA for use as monotherapy, and in combination with other antidiabetic agents, as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. It is a selective and reversible inhibitor of sodium-glucose cotransporter 2 (SGLT2) that works independently of insulin to help remove excess glucose from the body. Dapagliflozin, an investigational compound in the U.S., was the first SGLT2 inhibitor to be approved anywhere in the world. Dapagliflozin is currently approved for the treatment of adults with type 2 diabetes, along with diet and exercise, in 38 countries, including the European Union and Australia.

The EMDAC was provided with data from the extensive dapagliflozin global clinical development program included as part of the New Drug Application (NDA) and resubmission. In response to the FDA’s Jan. 2012 complete response letter, the NDA resubmission included several new studies and additional long-term data (up to four years’ duration) from previously submitted studies, resulting in an overall increase in patient-years exposure to dapagliflozin of more than 50 percent as compared to exposure in the original NDA. The resubmission included data from the dapagliflozin Phase II/III clinical development program, which included more than 11,000 adult patients with diabetes (approximately 6,000 patients received dapagliflozin) in 24 clinical trials.

Patient populations examined covered the range of diabetes progression, including drug-naïve patients, patients inadequately controlled on oral therapies and patients on insulin-based regimens. The program also provided significant experience in elderly patients, patients with a history of cardiovascular (CV) disease, overweight and obese patients, patients with poorly controlled hypertension and patients with mild to moderate renal impairment. In accordance with FDA guidelines, the NDA resubmission also included data assessing the CV safety of dapagliflozin in adults with type 2 diabetes. Additionally, the DECLARE study is being conducted in patients with type 2 diabetes to determine the effect of dapagliflozin, when added to the patients’ current anti-diabetes therapy, on the risk of CV events, such as CV death, myocardial infarction or ischemic stroke, compared with placebo. The randomized, double-blind, placebo-controlled study of more than 17,000 patients initiated enrollment in April 2013 and has an anticipated completion date of 2019.

Diabetes is estimated to affect 26 million people in the U.S. and more than 382 million people worldwide. The prevalence of diabetes is projected to reach more than 592 million people worldwide by 2035. Type 2 diabetes accounts for approximately 90-95 percent of all cases of diagnosed diabetes. Type 2 diabetes is a chronic disease characterized by several pathophysiologic defects, including insulin resistance and dysfunction of pancreatic beta cells, leading to elevated glucose levels. Over time, this sustained hyperglycemia contributes to further progression of the disease. Significant unmet needs still exist, as many patients remain inadequately controlled on their current glucose-lowering regimen.

The kidney plays an important role in maintaining normal glucose balance, in part by filtering and subsequently reabsorbing glucose back into circulation. SGLT2, a sodium-glucose cotransporter found predominantly in the kidney, is responsible for the majority of glucose reabsorption in the kidneys. In patients with type 2 diabetes, the capacity of the kidney to reabsorb glucose is increased by approximately 20-30 percent, further exacerbating the hyperglycemia associated with the disease. Selective inhibition of SGLT2 reduces the reabsorption of excess glucose and enables its removal via the urine.

In other FDA action, ALK announced today that the agency’s Allergenic Products Advisory Committee has voted unanimously that the available data support the efficacy and safety of Merck's GRASTEK™ in patients aged five to 65. The committee further recommended that adrenaline auto-injectors should be made available for patients at home.

GRASTEK is the proposed U.S. trade name of the grass sublingual allergy immunotherapy tablet, licensed to Merck (known as MSD outside the USA and Canada) for North America by ALK, and marketed in Europe under the brand name GRAZAX®.

The FDA is currently reviewing Merck's Biologic License Application (BLA) for GRASTEK for the treatment of grass pollen induced allergic rhinitis, with or without conjunctivitis, in adults and children of five years and older.

Jens Bager, ALK's President and CEO, said: "ALK welcomes the FDA Advisory Committee's conclusion, which represents another important step towards bringing this innovative new treatment to U.S. patients."

Although not binding, the FDA will consider the committee's recommendation as it completes its review of the BLA for GRASTEK, a process that is expected to be concluded during the first half of 2014.

ALK is a research-driven global pharmaceutical company focusing on allergy prevention, diagnosis and treatment and claims to be the world leader in allergy immunotherapy - a unique treatment of the underlying cause of allergy. The company has approximately 1,800 employees with subsidiaries, production facilities and distributors worldwide. ALK has entered into partnership agreements with Merck and Torii to commercialize sublingual allergy immunotherapy tablets in North America and Japan, respectively. The company is headquartered in Hoersholm, Denmark.

ALK has entered into a strategic partnership with Merck to develop, register and commercialize a portfolio of sublingual allergy immunotherapy tablets against grass pollen, ragweed and house dust mite allergy in the USA, Canada and Mexico. Under the agreement, ALK will receive up to $290 million in milestone payments from Merck. ALK is entitled to royalty payments on the net sales of the products on the North American market as well as payments for product supply. Merck will be responsible for all costs of clinical development, registration, marketing and sales of the products in North American with ALK being responsible for tablet production and supply.