August 11, 2014
The novel inhaled insulin product, Afrezza, recently approved for use in the United States, will be launched there at the beginning of next year following a commercial agreement signed between the manufacturer, MannKind, and pharmaceutical giant Sanofi.

The 2 companies announced the deal today, which sees Sanofi granted an exclusive worldwide license to develop and commercialize Afrezza, a rapid-acting human insulin powder for inhalation, for the treatment of adults with type 1 or type 2 diabetes.

The agreement will be seen as key to securing the immediate future of Afrezza; analysts had expressed concern that MannKind, as a small company, may struggle to get the product up and running given that it was approved by the US Food and Drug Administration (FDA) under a risk evaluation and mitigation strategy (REMS).

Afrezza will have a boxed warning advising that acute bronchospasm has been observed in patients with asthma and chronic obstructive pulmonary disease. The REMS is required to ensure that the benefits of Afrezza outweigh the potential risk of acute bronchospasm in patients with chronic lung disease.

Also, the FDA required 4 postmarketing studies as a condition of approval: 1 to evaluate the pharmacokinetics, safety, and efficacy of Afrezza in pediatric patients; another to assess the potential risk for pulmonary malignancy with Afrezza, along with assessment of cardiovascular risk and long-term effect on pulmonary function; and finally 2 pharmacokinetic-pharmacodynamic euglycemic glucose-clamp clinical trials, 1 characterizing dose response, the other within-subject variability.

Agreement Worth Up to $925 Million

Under the terms of the agreement, Sanofi will be responsible for global commercial, regulatory, and development activities. Under a separate supply agreement, MannKind will manufacture Afrezza at its plant in Danbury, Connecticut. The 2 companies will collaborate to expand manufacturing capacity to meet global demand “as necessary,” they say in a statement.

MannKind will receive an upfront payment of $150 million and potential milestone payments of up to $775 million. The milestone payments are dependent upon specific regulatory and development targets, as well as sales thresholds.

Sanofi and MannKind will share profits and losses on a global basis, with Sanofi retaining 65% and MannKind receiving 35%. Sanofi has agreed to advance to MannKind its share of the collaboration’s expenses up to a limit of $175 million.

“Afrezza is an innovative drug-device combination product consisting of a dry formulation of human insulin delivered through a small, discreet inhaler,” said Pierre Chancel, Sanofi senior vice president, diabetes division.

“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,” he added in the statement.

“We are so very pleased and honored that Sanofi has joined with MannKind to bring Afrezza to patients with diabetes worldwide,” added Alfred Mann, MannKind’s chair and chief executive officer.

“Sanofi is the ideal partner given their complementary product portfolio, their vast insulin market presence, and a leading global commercial infrastructure. Our profit-sharing agreement aligns the interests of MannKind and Sanofi to optimize development, commercialization, and manufacturing costs.”

Time Will Tell Whether Afrezza Is a Success or Not

Designed to be administered at the start of a meal, Afrezza dissolves rapidly upon inhalation to the deep lung and delivers 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.

Afrezza must be used in combination with a long-acting insulin in patients with type 1 diabetes. It is not recommended for the treatment of diabetic ketoacidosis or for patients who smoke.

It remains to be seen whether Afrezza proves a success or not. An earlier inhaled insulin, Exubera, developed by Pfizer and approved in 2006, was pulled from the market in 2007 because of low uptake.

However, there are some reasons to be optimistic that Afrezza will prove more successful: the Afrezza device developed to dispense the inhaled insulin is far smaller than the Exubera inhaler; the dosing is simpler; and Afrezza appears to be less likely to cause weight gain and severe hypoglycemia than standard insulin.

However, it is still not known how much Afrezza will cost and how the price will compare with other insulin products. Finally, there is concern as to whether physicians will want to switch patients to Afrezza.

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