60+ Old Studies

[brotherm1]

I see bits and pieces of thoughts about this subject but have not seen a thread devoted to it. So here it is. Who has the best guess of why we’ve not heard about them until very recently and why they are thought to be of importance? Perhaps it’s only one or a small amount of these studies of the alleged 60+ that had something inside that created an epiphany? My head is often like a sieve, I don’t even recall what Mike’s exact words were when he first mentioned this subject. Perhaps there are conspiracy theorists on board here that think someone inside MNKD was in cohoots with BP and hid these out of view? Just joking about this last question, I think.

[compound26]

IMHO, it probably is mainly due to the inexperience of the the previous management team at Mannkind at managing the trials and analyzing and using the data.

Prior to 2014, Mannkind was just laser focused to get Afrezza approved by FDA and they did not think too much about non-inferiority vs superiority. 

After 2014, once the partnership agreement with Sanofi is signed, Mannkind handed Afrezza to Sanofi and basically sits there doing nothing (in terms of trials, data mining, publication, etc.). I think Hakan is really to be blamed for this. Of course, more fatal mistake for them is the failure to raise more capital in 2014 and 2015. Not sure it is Al Mann's or Hakan's call on this.

Then as of Jan. 2016, after Sanofi handed Afrezza back to Mannkind, Mannkind has been scrambling to survive. Matt probably had his hands tied and couldn't do much at that point. 

So I agree with Mike's assessment and inspiration, 2016 is survival, 2017 is stabilization and 2018 is growth.  The STAT trial and hiring of Dr. Kendall seems like a 1-2 punch that will launch Afrezza to growth trajectory.

[dreamboatcruise]

Mar 21, 2018 12:57:53 GMT -5 brotherm1 said:

I see bits and pieces of thoughts about this subject but have not seen a thread devoted to it. So here it is. Who has the best guess of why we’ve not heard about them until very recently and why they are thought to be of importance? Perhaps it’s only one or a small amount of these studies of the alleged 60 that had something inside that created an epiphany? My head is often like a sieve, I don’t even recall what Mike’s exact words were when he first mentioned this subject. Perhaps there are conspiracy theorists on board here that think someone inside MNKD was in cohoots with BP and hid these out of view? Just joking about this last question, I think.

We've known that there were lots of studies.  They weren't a secret nor lost.

MNKD went above and beyond in doing various safety studies related to cancer risk, immunological, etc.  To me they seem pretty compelling.  One of the reasons I took such a financial risk on MNKD.  However, they aren't long term, large population trials, such as the FDA is requiring post market.  Those that are more conservative, and those that are against Afrezza (the competition), will argue that it's not definitive until the long term safety trials required by FDA are completed.

We also know that there were efficacy trials that were not accepted by the FDA for Afrezza because they were done with an older inhaler.  I imagine right after the FDA approval MNKD management probably assumed things would go great with SNY and that a whole round of new trials with dreamboat and optimally designed to show superiority would ensue.  I think we're left "rediscovering" these old studies because MNKD hasn't been able to afford new ones.  If Dr. Kendall manages to convince FDA to consider some of the pre-dreamboat data to improve the current label I will be very impressed.  There might be some small chance of that.  There is new management at the FDA and policies/priorities can change.  To me it appears that dosing and titration was still not fully understand even after Afrezza approval, so I would think that new studies with optimal dosing, use of CGM, etc. would be even better than any of these old results.

I wouldn't put too much stock in the idea that everyone here on proboards knows more about Afrezza than did Matt, Urbanski and Mike.

I'm not saying they aren't putting in place a strategy to try to better leverage these old studies, but as for what Mike has said, keep in mind that he is always trying to present new reasons to be optimistic (it's his job).  Remember, there was an awful lot of talk of the label change and how important that was going to be.  It's important, but obviously it wasn't a holy grail.  These old studies aren't the holy grail either.

[sayhey24]

Here is some history. Al assumed afrezza would be approved on the first submission. After all, he was only asking for human insulin which was already approved to be re-approved for administration through the inhaler. What Al did not appreciate was there was huge BP pressure on the FDA not to improve. Pfizer helped the cause by throwing the lung cancer "red herring" into the mix and pulling Exubera from the market.

After approval on the first submission, the plan was to qualify the dreamboat; re-submit for FDA approval; sign the partner; re-do some of the lost studies with the dreamboat; build out the factory; and get the FDA approval.

Well, that did not happen. The first CRL happened and then the Shkreli CRL happened and then it took 2 more years before approval. Al's health started to fail, the target partner had manufacturing concerns, Vienbacher stepped to the plate and signs the deal, and then Vienbacher gets canned. Al's health goes down hill fast, Brandicourt is focused on Toujeo, Stefan Schwartz sees its going to take a different approach selling to the T2 market and starts Onduo, its announced DeSisto is taking over, then Sanofi bails, then Desisto bails, the market assumes the "closed" sign is going and Jason Karp puts his 15cent pps target, Mike shows up out of the blue, Matt starts having health issues with his eyes and everything is a big mess.

For some period of time there was no CMO, then we had Ray who was not a diabetes guy, then we had no CMO again. Then we have Mike giving interviews and says a few things which seem odd, like he never read the old studies. Then we have a few old time investors ask about the old studies, Mike finds them, gives them to Dr. Kendall and the next things you know Dr. Kendall comes to MNKD.

Full disclosure - some of the time-line may not be 100% accurate but its pretty damn close.

I just think Mike was not aware of all of Al's work. He had no history with the company and Al was not there to let him know. Unlike Dr. Kendall's due diligence which was reading the studies, Mikes due diligence before coming to MNKD was talking with the original afrezza users and social media.

[dreamboatcruise]

Mar 21, 2018 13:53:50 GMT -5 sayhey24 said:

Here is some history. Al assumed afrezza would be approved on the first submission. After all, he was only asking for human insulin which was already approved to be re-approved for administration through the inhaler. What Al did not appreciate was there was huge BP pressure on the FDA not to improve. Pfizer helped the cause by throwing the lung cancer "red herring" into the mix and pulling Exubera from the market.

After approval on the first submission, the plan was to qualify the dreamboat; re-submit for FDA approval; sign the partner; re-do some of the lost studies with the dreamboat; build out the factory; and get the FDA approval.

Well, that did not happen. The first CRL happened and then the Shkreli CRL happened and then it took 2 more years before approval. Al's health started to fail, the target partner had manufacturing concerns, Vienbacher stepped to the plate and signs the deal, and then Vienbacher gets canned. Al's health goes down hill fast, Brandicourt is focused on Toujeo, Stefan Schwartz sees its going to take a different approach selling to the T2 market and starts Onduo, its announced DeSisto is taking over, then Sanofi bails, then Desisto bails, the market assumes the "closed" sign is going and Jason Karp puts his 15cent pps target, Mike shows up out of the blue, Matt starts having health issues with his eyes and everything is a big mess.

For some period of time there was no CMO, then we had Ray who was not a diabetes guy, then we had no CMO again. Then we have Mike giving interviews and says a few things which seem odd, like he never read the old studies. Then we have a few old time investors ask about the old studies, Mike finds them, gives them to Dr. Kendall and the next things you know Dr. Kendall comes to MNKD.

Full disclosure - some of the time-line may not be 100% accurate but its pretty damn close.

I just think Mike was not aware of all of Al's work. He had no history with the company and Al was not there to let him know. Unlike Dr. Kendall's due diligence which was reading the studies, Mikes due diligence before coming to MNKD was talking with the original afrezza users and social media.

To be clear, these are things you are guessing, correct?  Or do you actually have first hand knowledge of what each of them did and did not do?

[sayhey24]

I don't think I am guessing at much. After the each of the CRLs I has long discussions with Al. You are correct about the beginning of the first sentence but I think Mikes is correct. However I will be surprised if I am wrong about Dr. Kendall's due diligence. Off hand I can't remember what happened after Richardson but then Urbanski showed up.

[agedhippie]

If you go to the clinical trials site and put in Mannkind as the search term there are 47 studies that have been completed, terminated, or withdrawn. That includes all the non-insulin trials as well. Those are the trials Mannkind can talk about, anything else is internal only.

[tiberious]

Mar 21, 2018 14:26:16 GMT -5 agedhippie said:

If you go to the clinical trials site and put in Mannkind as the search term there are 47 studies that have been completed, terminated, or withdrawn. That includes all the non-insulin trials as well. Those are the trials Mannkind can talk about, anything else is internal only.

SayHey is pretty spot-on... makes me wonder if he used to work for the company like I did for 10 years in Paramus NJ.  When Mike took over the MKC Paramus site including all its output (trials, stats, delivery of NDA's and ultimate approval in 2014 etc.) was a footnote along with all but a few employees who transferred to Danbury.  Paramus housed the Clinical/Regulatory/BioStatistics functions and most of the medical professionals from 2005 to April 2015.  After the last major RIF (Oct 2015) most of the professionals who started the studies and worked on the were gone including the oncology researchers in Valencia.

The company didn't have any money for trials hence the RIF... Trial data archives sent to Danbury and that's it. 

[akemp3000]

My guess is that all of the 65 studies mentioned by Mike yesterday contain valuable data. Once evaluated and summarized by Dr. Kendall, answers to many past questions should be more easily communicated and accepted by doctors. I'm hopeful the cumulation of this data will better address and support Afrezza titration, lung delivery, less hypo events, no weight gain, the PK/PD profile advantage and more. I envision Dr. Kendall creating a spreadsheet listing these topics and where each intersects within the studies. Moving forward, Mannkind will be much better prepared when presenting information at U.S. and global conferences not to mention returning to the FDA for label improvement when possible. IMO, once Dr. Kendall gets solid footing, he'll help Mannkind win the debate of Afrezza versus existing standards of care especially the conversion from A1c to time-in-range. Even though powerful BP's currently control the global diabetes market, I would not want to represent them in a debate with Dr. Kendall once he's loaded with the data.

[mnholdem]

One of the big issues is that Afrezza is a drug+device combo. When MannKind switched to the Gen2 (Dreamboat) inhaler, the Gen1 data could not be used. But the Technosphere powder is the same.

Dr. Kendall will need to convince the FDA that the Gen1 trial results are applicable today. I think there is a good chance that he will succeed.

[mannmade]

I believe that was done with the 170 study for bio equivalency to the old inhaler if I remember it correctly. That should be the bridge to the past studies.

[digger]

I doubt that data mining old studies will convince insurers to provide better coverage.

[sayhey24]

You know what they say whats old is new again. Let me see - Digger, a really smart guy posting on PB vs. Dr. Kendall one of the biggest names in the diabetes community.   I don't know but my money is with Dr. Kendall, just saying. He might actually know what he is doing.

[mnholdem]

Mar 21, 2018 22:00:05 GMT -5 digger said:

I doubt that data mining old studies will convince insurers to provide better coverage.

How human physiology responds to an active pharmaceutical ingredient doesn't change over a mere decade, my friend.

[agedhippie]

What I don't see is where these 65 studies are since only 47 are listed in the Clinical Trials site for all Mannkind trials including the non-Afrezza ones and abandoned trials. Things like the hypo results from the Type 1 trials matter and I never understood why they were not used.

What we need is a new superiority trial. That's what will move sales.