OK, take a deep breath, Diabetes Friends.
Go on: Inhale, Exhale, Inhale, Exhale.
You know why -- there may soon be a new type of insulin on the market, the second attempt at a viable inhaled insulin since Pfizer's Exubera product fizzled seven years ago.
On April 1, an FDA advisory panel gave a thumbs up to MannKind Corp.'s inhaled insulin Afrezza, which would be used specifically for meal-time doses to prevent post-prandial blood sugar spikes and would be quick and easy to dose via a tiny inhaler device that fits in the palm of your hand (and looks like a whistle).
The FDA has extended its deadline for three months -- until July 15, 2014 -- to do a full review and determine whether Afrezza should be approved. Given the nearly-unanimous advisory recommendations, hopes are high!
- It's an ultrarapid-acting insulin in powder form that's designed as a pre-meal insulin for adults with type 1 or type 2 diabetes. It's aimed at post-meal blood sugar spikes, used with existing insulin treatment for basal coverage, so not meant as a stand-alone insulin therapy.
- The powdered insulin goes into the whistle-sized inhaler called the Dreamboat, which was developed after MannKind's first FDA round, and caused delays because the agency wanted more clinical studies comparing this new inhaler to the original.
- The powder dissolves immediately when inhaled into the lungs, and the insulin's then quickly dumped into the bloodstream to start working. Afrezza peaks within 12 to 15 minutes and is out of the system within an hour, compared to current fast-acting insulins that usually take at least 20 minutes to kick in, peak at 2-3 hours, and can stay in the system for as long as five hours.
- Each single-use cartridge of Afrezza insulin would be either 3 units or a double-dose of 6 units. MannKind CFO Matt Pfeffer tells us they're also planning 9 and 12-unit cartridges once they get initial FDA approval.
- The Dreamboat is disposable, meant to be thrown away after 15 days to prevent any powder buildup inside that could clog the device. And unlike traditional insulin, you don't have to refrigerate it.
Here's a YouTube video of how the Afrezza Dreamboat inhaler works, posted by a clinical study participant last year:
So it seems that a workable inhalable insulin product may be in our futures very soon! Note that a small San Francisco-based outfit called Dance Pharmaceuticals is also working on a similar product; the company is founded by people who worked on the original Exubera team, and their new Adagio product is based on "reformatting the Exubera formulation." Clinical trials for that kicked off last summer.
The Inhalable Saga
It's been a long road getting to inhalable insulin, especially for California-based MannKind, which has been trying to have its Afrezza product cleared by the FDA for five years now. Of course, we've been following the Afrezza story for years here at the 'Mine -- from the initial FDA filing days with the clunkier inhaler design, to the more recent coverage on how Afrezza's been used in Artificial Pancreas clinical trials.
The company first submitted a new drug application in May 2009 (back when it was spelled Afresa!), and regulators have twice turned the product down, asking for more clinical study data to appease concerns about safety and effectiveness. In 2011, the FDA asked for more data after MannKind switched inhalers during the review process.
Before last fall's resubmission, we heard MannKind boast about its successful Phase III clinical studies last summer that included 500+ type 1 PWDs in the U.S. and globally, indicating the company was ready to try its hand again with the FDA. In October, MannKind resubmitted Afrezza for regulatory review and is now hoping the third time will be a proverbial charm for final FDA approval.
The agency was initially set to decide by April 15, but earlier this week extended the full review deadline by three months. MannKind's Pfeffer tells us this gives the company more time to court potential partners, but also to work with the FDA on any labeling requirements that might be considered on the heels of the advisory panel's notes.
In terms of cost, Pfeffer says MannKind plans to make Afrezza as comparable as possible to insulin pens, which generally range from the low $100s up to $200. Of course, the company's been discussing insurance coverage with reimbursement experts, and while there's interest, much depends on the FDA approval and ultimately if MannKind finds a partner in the pharmaceutical industry to help market and sell Afrezza.
The April 1 Advisory Meeting
No April Fool's -- it was a bit of a surprise that Afrezza got a favorable recommendation, considering the agency's own staff review, that called the product "marginally effective" and "possibly risky." The committee voiced longstanding concerns that long-term exposure of the lungs to insulin could cause lung cancer, since clinical trial data showed more cases of lung cancer among those who received Afrezza than others in control groups. But the numbers were small and far from definitive, and with the requirement that MannKind undertake a long-term study to assess that risk, FDA was on board.
The committee voted 13 to 1 that Afrezza was safe and effective enough for approval as a treatment for type 1 diabetes, with the lone dissenter David Cooke voting that the risks outweighed the benefits. He pointed to the internal FDA review that showed some patients taking Afrezza stopped treatment after developing bronchial spasms, coughing, and a decline in the functioning of their lungs. But none of those concerns came up when voting on Afrezza for type 2, and the committee agreed unanimously to that.
"As an inhaled form of insulin, this represents a drug that will serve some patients that are not effectively served by currently available insulin," said Committee Chair Dr. Robert J. Smith, an endocrinologist at the Alpert Medical School at Brown University.
There was a lot of patient voice present at the FDA panel's meeting. Our friends from the think tank/newsletter diaTribe were there, not only speaking in favor of Afrezza but reporting on the meeting for those of us who couldn't attend.
Rebecca Killion: "Afrezza isn't a perfect drug. I've yet 2meet a perfect drug. 2say injection=inconvenience doesn't do it justice." #emdac — diaTribe (@diaTribeNews) April 1, 2014
Even if the FDA does give it a green light, there's no guarantee Afrezza will see commercial success or that PWDs will flock to use it. As of now, MannKind doesn't have any Pharma partners ready to sell Afrezza.
Of course, MannKind claims that Afrezza's different, mainly because Exubera used a clunky foot-long inhaler (aka "the bong") and was linked to a higher lung cancer risk that Pfizer just couldn't overcome.
We'll see what the D-Community thinks now with Afrezza, especially with all the AP clinical trial attention it's had recently. Whether that's enough to convince the masses is not yet clear... we'll just have to inhale the news for now, and see how long it takes until we can exhale, when the excitement turns into actual sales.