MedTone results in trial 171

[vdhingra]

I was thinking about this last night.

If the MedTone C Arm in the 171 were to have failed non-inferiority vs. RAA, what implications, if any, does that have for approval?

I think the MedTone HBA1c reduction in 171 was -0.13% (DB was published at -0.21%; and Mgmt. acknowledged a 0.08 diff between the two devices; which likely was on the downside) - which BTW is exactly what the MedTone C reported for 009 Trial, also a T1 trial.

The 171 results then would read: MedTone -0.13%; DB -0.21%; RAA -0.40%.

The diff of MedTone to RAA then would be 0.27%, and the upper limit of 95% CI, likely 0.10 -0.44 if we use the same +, - 0.17 range as DB, would above 0.40 thus establishing MedTone inferiority to RAA (I guess that’s the reason, Mgmt. kept saying that MedTone efficacy was never a Primary End Point).

So assuming that MedTone failed on PEP vs. RAA, what implication does that have for Approval.

From what was published, seems MedTone and DB individually comparable were on HBA1c, just not against RAA. The FEV for DB and MedTone were also comparable.

On the positive side one could argue DB seems to have narrowed the gap on HBA1C (MedTone -0.13% trials 009 and 171 vs. DB -0.21% 171), so it’s a better devise. On the othEr hand one could also argue whole bunch of if’s and but’s and what's. 

Appreciate any insights.

[alcc]

vdhingra,

I think you have put your finger on the one critical parameter (A1c) where there is some risk due to lack of visibility/disclosure. As you know, this has been siezed upon by bashers and shorts. We know DB putatively met PEP but is numerically inferior to RAA. We know MedTone gave slightly different results from DB. But it is not clear (at least I am not aware) in which direction (+ or -) and how FDA would look at the difference in the two arms. I am hoping adcom will actually help our cause by bring a broader perspective to the issue of A1c control. A narrow focus on A1c would not be helpful.

[jpg]

I was thinking the difference was the other way and that DB might need slightly higher doses then they first thought. regardless of this I don't think this would make a huge difference to the FDA but then again I don't have much insight as to what the FDA thinks and why...

JPG

[vdhingra]

Was just wondering on what weak A1c for Medtone in 171 may mean for the NDA. Based on the responses received, don't folks think it means much. And I certainly hope that is the case.

[spiro]

Vdhingra, here is a thread from the YMB that might help you understand this rather distracting issue. Do a Medtone c arm search at the YMB, this issue has been discussed there quite a bit.  


Reply to MNKD FACT vs FICTION by dtrouble1003 •Feb 4, 2014 2:22 PM
pfg_01 • Feb 5, 2014 4:18 AM

...your post makes absolutely no sense Rapp. The FDA rejected Afrezza last time because of changes to the delivery device. E.g. tests were conducted using the Medtone C inhaler and not the Dreamboat inhaler. Because Afrezza is inhaled, the FDA wanted a full clinical trial bridging the pulmonary data. The FDA was the one that approved the test's design and protocols.

With the bridge between trials established, all the data from all the trials is now included for consideration by the advisory committee as well as the FDA themself. So the data from the secondary end points in the 171 trial is merged with the data from similar endpoints in other trials. The consolidate data for the similar endpoints, both primary and secondary, clearly provide the positive data the FDA needs to approve Afrezza this time around.

Within the last couple of years, the FDA has approved several diabetic drugs on their third NDA submissions. In addition, approval rate for first time adcoms is extremely high. So using your statement that history "has a tendancy to repeat itself", then one can fully expect Afrezza will be approved this time around.

However, even though your post made "no sense" Rapp, I want to thank you for bumping dtrouble103's original post above. Less
4users liked this postsusers disliked this posts2Reply
I now think that HbA1c on the 3rd 171 arm is irrelevant
by dereklinders • Feb 4, 2014 8:49 AM
Mannkind did not report HbA1c efficacy numbers on the Medtone + Basal arm on 171. I was quite concerned about this, but no longer. Here's why:
Brentie pointed me to this November 4, 2011 quote from Peter C. Richardson - Chief Scientific Officer and Corporate Vice President
... More
Sentiment: Buy
Reply to A question regarding previous inhalants that failed and the FDAs letters to MNKD. by blockfrom3062 •Feb 8, 2014 1:01 AM
dereklinders • Feb 9, 2014 7:23 AM
2users liked this postsusers disliked this posts0Reply
To the question:
MNKD has not shared the CRL letters publicly, but from what they have shared:
... More
Sentiment: Buy
Reply to Why believe those who have no legal reason to tell the truth? I prefer to believe those who actually have the information. by dtrouble1003 •Jan 24, 2014 10:10 AM
rapp78 • Jan 26, 2014 3:31 PM
0users liked this postsusers disliked this posts2Reply
OPC, are you really that stupid? Who said anything about a Dreamboat inhaler? You have posted non-stop about this company for 5 years and you don't know that MNKD switched mid-stream from an older version of Medtone used in clinical trials to Medtone C which they used for marketing during their... More
Reply to I was intrigued by the superiority of Afrezza (study 171 results) in reducing Fasting blood glucose levels. by elmaestro11 •Feb 15, 2014 12:45 PM
pfg_01 • 22 hours ago
2users liked this postsusers disliked this posts1Reply
Does everyone want to know how absolutely stupid Rapp's logic is? The efficacy of Afrezza, which is what Rapp is talking about here, is based upon the amount of the drug that enters the blood stream. In the 142 trial, dosage bioequivalence was proven between the Medtone C inhaler and the Dreamboat inhaler, based upon a 3:2 ratio. So all the nonsense that Rapp just made up off of the top of his head about air flow problems, too cheap, too small, de clumping are just that...nonsense. Nonsense being, that it is not based upon any scientific facts, and completely contradicts the data from the applicable trials.

So with the same dosage of Afrezza entering the bloodstream between the two inhalers, why would there be the difference discussed? Because this is a secondary end point in which the trial population is insufficiently sized to establish statistical comparability between trials. The FDA states in their own documents, as well as in articles written by those that work with the FDA to approve drugs: that there can be significant variances in secondary endpoint data between trials, and that those evaluating drugs must be extremely careful in not reading too much into the data obtain from such secondary endpoints.

Of course, Rapp has either not done the research needed to understand how clinical trial data is analyzed, or if he has, then is trying to hide the knowledge so that he can twist the facts to his benefit. What is funny, is that is the very thing that the FDA warned might occur in evaluating secondary endpoint data. In other words, the FDA warned us to be aware of people like Rapp...LOL Less