I am responding to the most recent lies and innuendos posted by Adam Feurestein, posing as a "journalist." Let's go through his statements and see how he lies, places a negative spin at all costs and attempts to mislead investors or prospective investors.
1. RE Trial 134 (www.clinicaltrials.gov/ct2/show/NCT00642...), Adam Feurestein (NYSE:AF) states, "But if FDA doesn't also want to review data from this separate and equally large lung-safety study set to complete in 2015, why is Mannkind spending the money to run it?"
Let's first look at the timeline of events. Note, this trial was initiated in 2008. The two New Drug Applications (NDAs) were submitted on 3/16/09 & 6/29/10 and a third is expected this year before the completion of trial 134. If the FDA was concerned about pulmonary safety, wouldn't they have required it as a condition for the first submission, how about the second or third submission? Hmmmm. In fact, trial 134 isn't expected to be completed before 2015!
Sounds like the FDA is not concerned about pulmonary safety based on the volume of data already submitted. More on this in a bit. Further, does anyone not find it odd that the FDA would skip bringing Afrezza before a safety advisory panel either of two times the NDA's were submited if pulmonary safety were an issue? Would the FDA suggest Phase 4 trials in children 4 years old (MNKD's parameters were children no younger than 12 years old)?
Second, note this trial is for people who have lung conditions "Mild Obstructive Pulmonary Disease." Would the FDA allow testing in patients that would presumably be HIGHLY SENSITIVE to inhaled drugs if pulmonary safety were a concern among those without pulmonary issues?
Since AF is fathoming guesses, let me provide one. Management has consistently stated their preference to not have Afrezza used by those suffering from COPD. They seem to have moderated their stance. Trial 134 is being conducted to see how tolerable Afrezza is among people who already have lung issues. IOW, this would theoretically lower the threshold for those wishing to use Afrezza and actually increase the potential market for Afrezza, albeit not much. A cursory search shows that approximately 15% of diabetes population has COPD. There are 4 stages to COPD. Trial 134 only addresses the earliest stages which is an even smaller population.
2. In study 030 & 102 Afrezza experienced "poor tolerability and depressed lung function" in a previous study. AF cites 030 data presented at a 2009 European diabetes conference. Let's take a look at both of these studies and the data (http://www.mannkindcorp.com/Collateral/Documents/English-US/07-2009_EASD_030_Poster_920.pdf) he cited.
Here's the results of 030:
- "TI was noninferior to UC for mean change in FEV1 from Baseline to 24 months using Mixed Model Repeated Measure analysis with a prespecified non-inferiority margin of 50 mL/year"
IOW 030 was a noninferiorty trial and IT PASSED.
- "Subtle changes in pulmonary function have been reported in subjects with type 1 and type 2 diabetes treated with other inhaled insulin formulations."
IOW other inhaled programs experienced the same and Exubera was approved. Why should this inhibit Afrezza's approval?
- "Over 2 years, small declines from baseline in PFT's were observed in all groups, including the non-diabetic group. Decline was greater in TI group."
READ THAT AGAIN! Even those without diabetes showed a decline in lung function! Second, readers would be well served looking into the effects of DIABETES on lung function. Forget which medicine is used or how it's delivered, almost all diabetics experience pulmonary impact. It hasn't prevented other diabetes drugs from being approved.
- "Observed differences between TI and UC groups in the change from Baseline in lung functions were small, noted at the first post-Baseline assessment visit (3 months), and thereafter remained non-progressive over 2 years of continuous therapy."
IOW once the small impact was identified it didn't worsen.
- "Overall, rate of change in lung functions associated with the continued use of TI was similar to the rate of decline reported in subjects with diabetes in general."
The main take away from 030: Afrezza had more impact than other treatments but the difference was negligible. The FDA has twice reviewed Afrezza NDA's. If pulmonary function was an issue wouldn't trial 134 need to be completed BEFORE 2015? Before the next NDA (scheduled for '13)?
Trial 102 (http://clinicaltrials.gov/ct2/show/NCT00309244?term=mannkind+102&rank=2) was primarily an efficacy trial but pulmonary function was monitored as well. Drugs.com reported (http://www.drugs.com/clinical_trials/mannkind-reports-top-line-results-two-pivotal-phase-3-clinical-studies-type-1-type-2-diabetes-6547.html) "There was no between-group differences in pulmonary function measures, including FEV1 (forced expiratory volume in one second), FVC (forced vital capacity), DLCo (carbon monoxide diffusing capacity) and TLC (total lung capacity)."
But, wait. There's more. MNKD also did a follow up study to trials 009, 102, 103 and 030 (672 patients; http://clinicaltrials.gov/ct2/show/NCT00741429?term=NCT00741429&rank=1). This study's goal was to review pulmonary adverse events in the aforementioned trials. This trial was completed in 2008. Go back to the timeline I first laid out. You can see this data would have been submitted to the FDA as part of both NDAs. IOW, if the FDA had pulmonary concerns, MNKD would need trial 134 completed before a '13 NDA. Again, 134 is scheduled for completion in 2015! The FDA would have raised safety issues and forced Afrezza before a safety panel. That didn't happen. Is this starting to sound repetitive yet?? AF's arguments are shallow, baseless and the data clearly refutes his assertions.
2. AF states Results of 030 & 102 included in both new drug applications which were "rejected twice." Well, I think AF has some explaining to do. He either has inside information or he's lying. The NDA was rejected twice, but no one knows, including AF, whether it was due to the 030/102 trial results. However, I have clearly laid out the trial results from both trials plus another follow-up trial. All of them met their end points. If you know the story of the inhalers being switched and the in vitro testing I alluded to in another post, you likely know it had nothing to do with pulmonary safety. Sorry AF, but you do not lie very well at all.
3. AF then states, "Mannkind had long claimed the safety study showed no difference in adverse events or lung function between Afrezza-treated patients and those on usual care." Well, I just went through every transcript since the beginning of 2009 looking for references to the lungs or pulmonary function. Here's what I found (bold type provided by me):
- MNKD 10K (2/09) Transcript: "After a two-year Phase 3 clinical trial of AFREZZA, we determined that the use of AFREZZA in patients with diabetes was non-inferior to usual diabetes care with respect to a decline in FEV1, a measure of lung function that assesses the volume of air that can be forcibly expired within one second. Similar results were obtained for other measures of lung function."
- Q1'09 Transcript: "Mannkind has conducted extensive studies of the impact of AFRESA on lung function with no safety signals whatsoever. In most clinical trials, we saw no effect on pulmonary function at all. In summary, we have seen some tiny differences that are clinically insignificant. We see no meaningful glucose controlled differencing conditions such as asthma or respiratory infection or in smokers. We have seen so far found no conditions that would justify counter indication although we propose that AFRESA not be use in persons with significant loss of pulmonary function. Our studies have been carefully reviewed by a cadre of independent medical experts, not a single one has expressed any concern about pulmonary impact including cancer risk. Moreover, they have all stated their conclusions there is nothing that would support the need for any pulmonary function testing though we cannot say with certainty that the FDA will not require some PFTs."
- Q1'09 Transcript: "We presented a very robust package of pulmonary function data. Probably one of the largest that the agency have seen, certainly one of the largest that I know in terms of in passing an inhaled track, both data I think support very clearly no clinical indication using pulmonary function testing. In fact, when we talked about this and when we looked at the lack of outliers in our database and the lack of concerning changes in pulmonary function, we believe that the best tool for looking at this is to use a doctor's stethoscope and their own clinical acumen and deciding which patients are right for AFRESA. We said the patients with underlying lung disease will not be suitable."
- Q2'10 Transcript: "Moreover, we have carefully evaluated all adverse events and have presented to the agency an extensive safety package updating the safety experience, and showing no pulmonary damage or clinically significant pulmonary effect, no cardiovascular impact and no indication of any cancer risk. The only adverse effect likely associated with AFREZZA, is mild to moderate coughing in early use with some patients, because people are not accustomed to the feel of inhaling any powder, not just AFREZZA. This effect moderates with use and less than 3% of patients find it objectionable enough to discontinue."
- Q3'10 Transcript: "AFREZZA is well-tolerated and we've not identified any safety signals, though we will not recommend it for patients with compromised lung function."
- Q4'10 Transcript: "Tom, remember that we had only about a little over 2% to 3% reduction, clinically insignificant reduction that was non-progressive, happened early in the use and didn't change until we stopped and then it recovered. There was no aspect on pulmonary tissue and we now believe it was really probably just a reaction to inhalation by people. We don't have a lot of data with the new device, but with the new device, it appears to be even less, but is already clinically insignificant. So, the FDA just wants us to confirm that we are at least as good as MedTone."
- Q1'11 Transcript: "We recently had an end of review meeting with the FDA. And I did attend this meeting in person, and I'm pleased to report that the meeting was very productive. We achieved a great deal of clarification about the design of the 2 additional required trials, one in Type 1 diabetes and one in Type 2 diabetes. Much of the discussion was centered on the details of evaluating the pulmonary safety of Dreamboat versus MedTone in a head-to-head comparison. The agency agreed that the observed changes in pulmonary function do not differ between Type 1 and Type 2 patients. They also considerably simplified the requirements of pulmonary function testing by requiring spirometry alone as compared to the previous pulmonary safety studies, in which we also collected a more complicated, less generally available measurements DLCO and DLZ."
- Q2'11 Transcript: "As you know, we had an end-of-review meeting on meeting on May 4."….." We further refined the proposed protocol for the required Type 1 and Type 2 studies and reached agreement on several key issues. For example, the agency concluded that the pulmonary function measurements of DLco and TLC was not to be necessary. This reduction itself would simplify the studies and this relaxation of the requirement suggest that any pulmonary function testing in the final label will not become a significant marketing obstacle. After all, in all our testing, we have been only a tiny temporary effect on pulmonary function that has always been resolved at cessation, and is likely just a reaction to the powder inhalation."
- Q3'11 Transcript: "In our previous clinical program, we saw only a small clinically insignificant drop in pulmonary function that resolved upon therapy discontinuation."
- Q3'11 Transcript: "The agency has not raised any questions about safety for some time."
- Q3'12 Transcript: "we have seen no signals to raise any safety concerns about our formulation or our delivery. Both the insulin and the carrier quickly crossed into arterial blood, there is no accumulation in the lungs."
I have better things to do with my time than count the number of times management has referred to slight differences in pulmonary function. Therefore, AF is LYING WHEN HE STATES MANAGEMENT HAS LONG CLAIMED "no difference." Anyone need further evidence that AF is clearly lying to readers of thestreet.com?
4. Next AF states (study 030) "The drop-out rate for Afrezza patients was 49.4% compared to 30.4% in the usual car arm" So? Bottom line: 030 met it's primary endpoint. 'Nuff said!
5. Next AF states (study 030) Cough was the leading cause of discontinuation for Afrezza patients and was reported as an adverse event by 28% of Afrezza patients overall. Only 4% of patients treated with usual care reported cough as an adverse event. (they weren't given Afrezza). Ok, where to begin with this load of crap. You see, AF tries to imply that 28% experienced a cough and dropped out. Nice try AF! What's important is how many quit due to a cough. If you look at the Q2'10 Transcript I posted above, management has already answered this non-issue: "The only adverse effect likely associated with AFREZZA, is mild to moderate coughing in early use with some patients, because people are not accustomed to the feel of inhaling any powder, not just AFREZZA. This effect moderates with use and less than 3% of patients find it objectionable enough to discontinue." AF, show us your data to refute this….Scumbag.
6. AF states, (study 030) "Afrezza caused depressed lung function over two years." This has already been addressed. Note, AF doesn't state how much lung function is depressed. As I've now pointed out, it was negligible and didn't persist upon stopping usage.
Clearly, AF is attempting to depress the stock's price following a strong rise in price. He's now posted two pieces, both of which are full of false innuendos, lies, misrepresentations and ignorant conclusions. Why anyone would follow this tool is simply beyond me.
Disclosure: I am long MNKD.