Huge news, D-Friends: the new rapid-acting inhalable insulin known as Afrezza has just obtained FDA approval!
The third time's the charm for this new formulation of inhalable insulin, the second-ever to make it through the U.S. regulatory process after Pfizer's failed Exubera the better part of a decade ago.
On Friday, the California biotech company MannKind Corp. finally obtained regulatory clearance for its Afrezza device. Twice before, regulators turned down Afrezza asking for more clinical study data to appease concerns about safety and effectiveness.
Now, after resubmitting Afrezza in October 2013, MannKind has finally convinced the FDA it's ready to get into the hands of adults with diabetes!
We're told by MannKind's top executives that they're working to find a pharma partner to manufacture and distribute Afrezza, and the product could be made available as soon as January, or end of the first quarter of 2015.
In the FDA news release issued on Friday, Dr. Jean-Marc Guettier of the agency's Division of Metabolism and Endocrinology Products, states: "Today's approval broadens the options available for delivering mealtime insulin in the overall management of patients with diabetes who require it to control blood sugar levels."
Here's the 411 on Afrezza, for those who don't know:
Afrezza's an ultrarapid-acting insulin in powder form that's designed as a pre-meal insulin for adults (not yet for kids) with type 1 or type 2 diabetes. It's aimed at post-meal blood sugar spikes, meaning used with existing insulin treatment and not meant to be a stand-alone insulin treatment.
The powdered insulin is administered via a whistle-sized inhaler called the Dreamboat, which was developed after the first FDA round and caused delays because the agency wanted more clinical studies using that new inhaler. 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 short-term 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.
MannKind has spent years trying to gain approval for this treatment, first submitting a new drug application in May 2009. And now, Afrezza appears to be ready for primetime, having cleared the FDA.
Of course, the biggest appeal is that it requires no needles, but just a little hand-held inhaler that really does look like a whistle. The Dreamboat is meant to be thrown away after 15 days to prevent any powder buildup inside that could clog the device. Unlike traditional insulin, it needs no refrigeration, but rather is kept at room temperature. Each single-use cartridge would hold either 4 or 8 units, and by the time Afrezza is commercialized, there could be a 12-unit cartridge available.
Here's how you might dose for it, converting current insulin injection or bolus amounts into an Afrezza-friendly inhalable dose:
Personally, that doesn't seem like a lot of insulin to cover some of the meals I eat that require higher doses... I'd be going through a whole bunch of those little cartridges. So for some PWDs, this device may present a logistical challenge in terms of easily dosing the amounts we need...? But then again, this may be a good tool for knocking down stubborn high blood sugars with correction dosing.
In a phone conversation late Friday, MannKind's president Hakan Edstrom told us the company hasn't yet finalized any deals with potential partners in order to manufacturer and distribute Afrezza. But it's getting close, and in talks with a number of companies to finalize a partnership as soon as possible.
Costs remain TBD (a lot depends on the potential partnership), but Edstrom says they expect prices to be in the same range as what we patients typically pay now for insulin pens in the U.S.
This approval is a HUGE development, and it's been a long time coming, eight years since this quest began by Alfred Mann -- the man who founded Minimed before it was eventually bought by Medtronic. We've been following the Afrezza story for years here at the 'Mine -- from the initial FDA filing days when MannKind had its initial clunkier design, to the more recent coverage on how Afrezza's being used in Artificial Pancreas clinical trials.
So far it's cost a whopping $1.8 billion (!) to get Afrezza to this point, and much of that money was used to pay for 60+ clinical trials that have involved 6,500 patients. Wowza!
Before last fall's FDA resubmission, we heard MannKind boast about its Phase III clinical studies last summer that included 500+ type 1 PWDs in the U.S. and globally, which indicated the company was poised to try its hand again with the FDA.
All that said, it's still a bit of a surprise that Afrezza got the FDA's approval, considering the agency's own staff review had raised concerns about the product's safety and effectiveness. There were initial 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 MannKind was required to undertake a long-term study to assess that risk.
The advisory committee that met on April 1 of this year 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 for type 1s. 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 during the voting on Afrezza for type 2 use, and the committee decided unanimously in favor with a 14-0 vote.
In approving Afrezza, the FDA has attached a number of safety, effectiveness and patient use stipulations:
- It's not recommended for people with diabetes who smoke, nor for treating diabetic ketoacidosis (DKA).
- Afrezza is only approved for adults, not kids. However, the agency's asking for a post-market clinical trial to evaluate the safety and use in pediatric patients.
- The FDA is requiring a Boxed Warning, advising that some people with asthma and chronic obstructive pulmonary disease (COPD) who've used Afrezza have experienced acute bronchospasm. As a result, those with chronic lung disease, asthma or COPD, should not use Afrezza because of this risk. The most common adverse reactions associated with Afrezza in clinical trials were hypoglycemia, cough, and throat pain or irritation.
- Part of the approval requirements are a Risk Evaluation and Mitigation Strategy, which must include a communication plan to inform health care professionals about the serious risk of acute bronchospasm associated with Afrezza. That's mean to ensure that the benefits outweigh the potential risks of using Afrezza.
- Other post-market studies are required on Afrezza, such as: clinical trial to evaluate the potential risk of pulmonary malignancy with use (this trial will also assess cardiovascular risk and the long-term effect of Afrezza on pulmonary function); and two pharmacokinetic-pharmacodynamic euglycemic glucose-clamp clinical trials, one to characterize dose-response and one to characterize within-subject variability.
Edstrom told us they are planning to start pediatric trials as soon as possible, which will realistically begin sometime in mid-2015. That means Afrezza might not be approved for kids with diabetes until 2017, and that regulatory process may vary depending on what the post-market studies and adult-use experience shows in the meantime.
And despite the FDA green light, there's no guarantee Afrezza will see commercial success or that PWDs will flock to use it. As noted, MannKind has not yet secured any pharma partners ready to sell Afrezza. But if MannKind's earnings call in May is any indication of what's coming soon, a potential partnership may not be far off.
From the investor point of view, many are skeptical based on the failed Exubera inhaled insulin that has shaped much of the discussion about Afrezza over the past several years. That joint Pfizer-Sanofi product was pulled from the market in 2007 after more than a year's worth of subpar sales -- resulting in a record-breaking $2.8 billion loss for the vendors.
Of course, MannKind claims that Afrezza is significantly different, mainly because Exubera used a clunky foot-long inhaler 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 more recently. Whether that's enough to convince the masses is yet unclear...
Inhale the news for now, and we'll see how long it takes for us all to exhale and turn this excitement into actual sales and widespread use.