FDA updates Afrezza label to reflect ultra-fast PK/PD profile; Major win for MannKind – October 4, 2017

In a major win for MannKind, the FDA has approved a label update to reflect the faster onset/faster offset of inhaled mealtime insulin Afrezza. The company hosted a call with investors on Monday to discuss the implications of this label change – and there are many! – which is available online as a webcast replay. At a high level, the revised Afrezza label includes clinical trial data to show onset of insulin action within 12 minutes, peak effects within 35-45 minutes, and a return to baseline PK/PD ~1.5 hours after dosing with a 4-unit cartridge or ~3 hours after dosing with a 12-unit cartridge. This reinforces the product’s “ultra-rapid-acting” nature. Faster onset reduces unpredictability around meals for people with diabetes, while faster offset lowers the hypoglycemia risk stemming from residual insulin in the bloodstream (during the investor call, CEO Mr. Michael Castagna highlighted the “long tail” associated with most other mealtime insulin options). Mr. Castagna called this a “pivotal moment” in MannKind’s history, explaining that for the first time, promotional activities around Afrezza will not have to state that the product’s time-action profile is comparable to that of insulin lispro (Lilly’s Humalog). Instead, FDA has now advanced Afrezza into a new category of ultra-fast insulins, and the label update sets this therapy apart from others in its class. Management did not share too many details about how marketing strategy will shift in light of this label change, but we imagine the commercial impact of the FDA approval will be substantial (after all, this is long-awaited) and we’re hoping for more color on this during MannKind’s 3Q17 earnings call. Since the relaunch of MannKind-branded Afrezza in August 2016 (following termination of the Sanofi partnership), it has been our view that the company will be more successful emphasizing the faster-acting nature of its product rather than the inhaled aspect (though both contribute to patient convenience). With this positive FDA decision, MannKind is now better-equipped to do just that. The additional clarity on the dose-response effects of Afrezza will also be informative for patients/HCPs, helping more people with diabetes feel successful with inhaled boluses.

We’re very excited about what this label update means for patients, both type 1 and type 2. Feedback from those who use Afrezza has been largely positive, and many diabetes thought leaders have similarly endorsed this therapy, so any move that might get the product into the hands of more patients is a good one, in our view. Not only can sales reps now say more about the unique, distinguishing features of Afrezza, but management may be able to leverage the “ultra-fast” designation in formulary negotiations to expand access. As we recently learned, Afrezza is excluded from the UnitedHealthcare formulary, which is unfortunate and very troubling – we recommend this stirring blog post written by a patient who couldn’t get coverage despite benefiting enormously from the inhaled insulin. Moreover, this FDA approval could serve as a much-needed boost to the Afrezza business: Sales totaled $1.5 million in 2Q17, marking 25% sequential growth from 1Q17, but the franchise has yet to truly take off on the market. Commercial rollout of the label change will take some time – keep in mind that MannKind only became a full-scale commercial company in the past year, after focusing on manufacturing and R&D during the Sanofi partnership – but we’re keeping our fingers crossed for a steeper climb in Afrezza prescriptions/sales going forward.

• It has been an exciting few days for the rapid-acting insulin class, as Novo Nordisk’s next-generation Fiasp (faster-acting insulin aspart) was just FDA-approved on Friday. Mr. Castagna emphasized that Afrezza shows even more rapid onset/offset vs. Fiasp, on average. We see an opportunity for both these products to grow the class as a whole, as they have demonstrated compelling safety/efficacy as bolus insulins, with potential to cause less hypoglycemia and to improve patient quality of life. Insulin, and especially rapid-acting insulin, is a daunting drug for many people with diabetes – any advanced therapy that reduces uncertainty around meals and that expands patient choice within this class is something to celebrate, from our perspective. We see more than enough room for both Fiasp and Afrezza to gain commercial traction and be successful on the market.
• Mr. Castagna also pointed to the recent FDA approval of Abbott’s FreeStyle Libre as a growth opportunity for MannKind’s Afrezza. Currently, the split between type 1 and type 2 diabetes patients on Afrezza is about 50%/50%, even though type 1 comprises only ~5-10% of the real-world diabetes population while type 2 accounts for ~90-95%. He went on to state that FreeStyle Libre will appeal to many type 2 patients in the US, and that MannKind can capitalize on that to grow Afrezza prescriptions in this population as well.

-- by Payal Marathe and Kelly Close