NEW YORK (TheStreet) -- Another column in which I talked to myself, this time about MannKind (MNKD) and the inhaled, rapid-acting insulin Afrezza. An FDA-sponsored advisory panel convenes Tuesday to review Afrezza and issue a recommendation on whether or not the product should be approved for the treatment of Type 1 and Type 2 diabetes. The following made-up conversation previews tomorrow's Afrezza panel.
Adam, you previously gave 60% odds for a negative panel vote on Afrezza, but that was before the FDA weighed in with its clinical review on Friday. Where do you stand now on Afrezza's chances after reading the FDA's briefing materials.
The same 60% chance of a rejection by the FDA advisory panel. I'm more negative now on Afrezza in Type 1 diabetes -- I believe MannKind is in serious trouble there. For Type 2, the debate and vote will be closer. MannKind has a chance but a lot has to go right for them.
Going into the release of the FDA briefing material, many MannKind critics, including yourself, questioned whether the regulators would conclude that one or both of the Afrezza phase III studies had actually failed -- contradicting the claims made by the company. That didn't happen, so isn't MannKind's outlook for tomorrow better?
FDA didn't come out and say the Afrezza studies failed. That's true, but regulators weren't exactly effusive in their praise of the data, either. FDA described Afrezza's blood glucose-lowering efficacy as "modest" several times in its review while also raising questions about interpretations of the efficacy results.
For example, In the Type 1 diabetes study, the FDA raises concerns about background basal insulin levels that were significantly higher in the Afrezza arm compared to the control arm. Normalizing those basal insulin levels could have turned a narrowly positive study (Afrezza just barely squeezed by the statistical non-inferiority margin) into a negative one.
In the Type 2 study, FDA agreed with MannKind that Afrezza was superior to placebo for the primary endpoint of HbA1c reduction, but the agency also went out of its way to include "comparative effectiveness" data showing how Afrezza was inferior to almost all currently available Type 2 diabetes therapies.
Then, FDA raised concerns about Afrezza's lung safety, including a small, but higher incidence of lung cancer seen in Afrezza patients. Modest efficacy plus safety concerns is not a favorable balance for a drug seeking approval in a chronic condition like diabetes, especially one where patients have an abundance of effective medicines already available.
You admit MannKind has a decent chance to emerge from tomorrow's panel meeting with at least one positive vote recommending Afrezza's approval. What does the company need to do to make that happen?
As best it can, MannKind needs to keep discussion focused on the Afrezza data from the two studies, emphasizing the company did what FDA asked for in order to get its product approved. It's hard to imagine any of the panelists tomorrow being wowed by Afrezza, but if MannKind can demonstrate the data are good enough for approval, it may get a positive vote.
MannKind may have to concede away approval in Type 1 diabetes and also be very acquiescent about the need for additional, post-approval studies to better quantify Afrezza's long-term lung safety.
The day goes bad for MannKind if panelists or the FDA make a stink about the clinical utility of Afrezza relative to other diabetes therapies, or if the company comes across as argumentative or inflexible.
There is no FDA webcast of Tuesday's panel but you're live-blogging, correct?
Ah, thanks for the self promotion. Yes, I will be live-blogging the Afrezza panel. You'll be able to find a link to the live blog on TheStreet's home page, starting Tuesday at 7:45 am EDT. If you want to watch the panel yourself, FDALive.com provides a live web feed but the cost is $200.
Will MannKind trading be halted Tuesday?
I don't know for sure but I'd assume, yes, MannKind will not trade during the Afrezza panel meeting.
What time will the panel members vote on Afrezza?
You can download a copy of the agenda for Tuesday's panel. It's an all-day affair. The panel starts at 8 am EDT with introductory remarks by FDA. MannKind will present the Afrezza data to the panel first, followed by the FDA's presentation. If you can't log in to my live blog all day (and why not?!?!), the most important part of the meeting will take place probably between 3 pm and 5 pm EDT. That's when the panel members are expected to debate the Afrezza data and vote on whether or not to recommend approval.
MannKind supporters dislike you and believe you're biased against the company. Why should they bother to log into your live blog when all you're going to do is bash Afrezza and the company. Basher!
Not true! Well, I'm not a MannKind fan, that is true, but I've tried to make factual and fundamental arguments for why Afrezza is not the miracle insulin therapy its supporters believe it is. Disagreement is a good thing. With that said, I promise to give MannKind a fair shot during my live blog. You can ask fans of Amarin and Arena Pharmaceuticals how I treated the companies during their respective FDA advisory panels. They may still dislike me, but they'd also tell you, begrudgingly, that I was fair.
Let's get back to discussing the Afrezza studies. You mentioned above that MannKind might be in trouble with the Type 1 diabetes indication. Can you explain why?
Sure. The phase III study in Type 1s compares Afrezza plus basal insulin against insulin aspart plus basal insulin. (A third arm of the study uses the older "Medtone" inhaler but I won't discuss that here.)
At the end of the study, the mean decrease in HbA1c from baseline for Afrezza was -0.21 compared to -0.40 for insulin aspart -- a difference of 0.19. From a statistical standpoint, Afrezza was found to be non-inferior to insulin aspart because the upper bound of the confidence interval (0.36) was within the agreed-upon margin of 0.40.
That sounds like a lot of gobbledygook, but what you're saying is the Afrezza study in Type 1 diabetics was successful.
Yes, the FDA agreed that Type 1 Afrezza study met the primary endpoint of non-inferiority, but...
Uh oh, there is a but?