Sanofi will commercialize Afrezza® ( insulin human)—a rapid-acting inhalation powder recently approved for adults with type 1 and type 2 diabetes—under an exclusive licensing agreement that could net MannKind up to $925 million, the companies said today—and could help fill the revenue gap expected when the pharma giant’s blockbuster insulin glargine Lantus loses patent protection next year.
Sanofi will oversee global commercial, regulatory and development activities for Afrezza, and will retain a 65% share of global profits from the treatment, with MannKind keeping the remainder. MannKind and Sanofi plan to bring the inhaled insulin to market in the U.S. during the first quarter of 2015.
MannKind agreed to manufacture Afrezza at its manufacturing facility in Danbury, CT, and plans to collaborate with Sanofi to expand manufacturing capacity “as necessary” to meet global demand for Afrezza, the companies said.
In return, Sanofi agreed to pay MannKind $150 million upfront and up to $775 million in milestone payments tied to regulatory and development targets, as well as sales thresholds. Sanofi also agreed to advance MannKind its share of collaboration expenses, up to $175 million. The deal is subject to customary Hart-Scott-Rodino approval and completion of financing documentation.
Afrezza consists of Afrezza Inhalation Powder, delivered using an inhaler. Administered at the start of a meal, Afrezza is designed to dissolve rapidly upon inhalation to the deep lung, and deliver insulin quickly to the bloodstream. Peak insulin levels are achieved within 12 to 15 minutes of administration, and decline to baseline by approximately 180 minutes, according to MannKind.
"Afrezza is a further addition to our growing portfolio of integrated diabetes solutions. It is uniquely positioned to provide patients with another insulin therapy option to manage their diabetes but does not require multiple daily injections," Pierre Chancel, Sanofi’s svp for its Diabetes Division, said in a statement.
Sanofi’s diabetes portfolio is anchored by Lantus, a long-acting human insulin analog available in more than 120 countries worldwide. Lantus is the best-selling insulin glargine, with 2013 sales of €5.715 billion ($7.650 billion) – but those sales are expected to decline sharply once patent protection expires next year.
Other Sanofi-marketed products for diabetes include Apidra® (insulin glulisine) a rapid-acting human insulin analog; Insuman®, a range of rapid- and intermediate-acting human insulin products; Lyxumia® (lixisenatide), a once-daily prandial GLP-1 receptor agonist; and Amaryl®/Amarel® (glimepiride), a sulfonylurea-class hypoglycemic.
Afrezza would compete in part with two injectable rapid-acting insulins of shorter duration, Eli Lilly’s Humalog and Novo Nordisk’s Novolog—though rapid-acting products are often combined with long-acting insulins.
The licensing agreement comes less than two months after the FDA approved Afrezza. As is customary, FDA heeded the recommendation of its Endocrinologic and Metabolic Drugs Advisory Committee, which recommended approval of the drug in April—despite issues raised in a critical staff report. Among them: Some patients taking Afrezza stopped treatment after developing bronchial spasms, coughing, and a decline in the functioning of their lungs. Also, MannKind’s application for Afrezza cited cartridges containing up to three units of injected insulin, and double-strength cartridges with up to six units, when its clinical trial used cartridges with up to four units and double-strength cartridges of up to eight.
FDA sought to address safety concerns by requiring a black-box warning and including among limitations of use that Afrezza must be used in combination with a long-acting insulin in patients with type 1 diabetes; is not recommended for the treatment of diabetic ketoacidosis; and is not recommended for patients who smoke.
FDA had twice held off on approving Afrezza—most recently in 2011, when it issued a complete response letter after MannKind switched the drug’s inhaler during agency review. The FDA then required two additional clinical studies comparing the current inhaler to its first-generation MedTone inhaler. Last year, MannKind released positive results from the two Phase III trials.