The symbolic champagne bottles must have popped at Mannkind corporate headquarters on a Friday in late June; after years wandering in the regulatory wilderness, its product, Afrezza, received FDA approval. It has been a long and daunting process to get this product to market, with many regulatory hurdles, but the company persevered and its inhalable insulin product and Dreamboat inhaler now can hit the open market.
On June 27th, 2014, the FDA sent notice that it has approved Afrezza as a bolus insulin for adults with Type 1 and Type 2 diabetes, with some restrictions. FDA regulators agreed with the recommendation of its scientific advisory board that clinical trial results proved the inhalable insulin is safe for use and does what it is supposed to do as a rapid-acting insulin. Mannkind did exhaustive research on the matter, enlisting some 6,500 patients with diabetes to test Afrezza in clinical trials since 2009.
But, as with many new drug approval notices, the FDA’s greenlight notice to Afrezza wasn’t a complete ringing endorsement. For example, the FDA noted that Afrezza did not control A1C better than rapid-acting insulin currently on the market, and the difference was considered “statistically significant”. The FDA also directs that the inhalable insulin can only be used by adults with Type 1 diabetes who are also taking a long-acting (basal) insulin, for example. Children with Type 1 aren’t yet allowed to take it at all; the FDA has ordered more trials on this matter.
And it’s clear that the FDA still has concerns about how inhalable insulin will affect pulmonary function for some individuals. Regulators warn that Afrezza should not be used by patients with chronic lung disease, such as asthma or COPD, or people who smoke; patients with these symptoms or behaviors have been observed to suffer from acute bronchospasm, which can include coughing, wheezing, shortness of breath, and sore throat.The FDA also wants Mannkind to do additional testing to evaluate the “potential risk of pulmonary malignancy” and the effects Afrezza might have on long-term lung function.
It should be noted, however, that the FDA seemed to have many of the same lung function concerns with Exubera, the first insulin inhaler to hit the market. The 2006 FDA approval notice for Exubera also warned that people who smoke or with some pulmonary issues shouldn’t use the product, and it also noted that Exubera was going to undertake follow-up testing for long-term safety and the possibilities of lung disease. These warnings could be the FDA’s way of doing due diligence on all new inhalable medical products.
But while Mannkind can take comfort in Exubera’s safety track record, it now must run from that product’s legacy. Exubera, the pioneering inhalable insulin product, produced by Pfizer, was a monumental flop in the marketplace, aided in part by an unwieldy inhaler that spooked patients. Doctors didn’t push for the novel drug delivery, and insurance companies also frowned on covering the product because it didn’t provide as tight of blood glucose control as injectable rapid-acting insulin. In the end, the product was pulled; it ended up costing Pfizer some $2.8 billion in losses.
Mannkind has come up with a much less obtrusive inhaler, but they still must convince the marketplace to embrace Afrezza. To do that will cost money, and Mannkind might have to partner with a bigger company to do a successful rollout. Still, FDA approval is Mannkind’s ticket to the dance, and that means it’s time to see what Afrezza can do for people with diabetes.