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Post by suebeeee1 on Sept 14, 2015 17:59:41 GMT -5
Frankly, it really doesn't matter whether this study ends in 2016 or 2019. If the drug is approved for the pediatric population, the patent is extended. Gives us more time overall!
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Post by harrys on Sept 14, 2015 18:31:20 GMT -5
Is the pediatric trial a definite obstacle for perdiateic use or just to attain pediatric "reccomendation"? Otherwise pediatric is more than two years out... by then things with MNKD will have been hashed out one way or the other regardless.
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Post by ezrasfund on Sept 14, 2015 18:38:45 GMT -5
A doctor could prescribe Afrezza but probably would not for children. A 16 year old is still off label, but I think we have had some reports teenagers using Afrezza.
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Post by peppy on Sept 14, 2015 18:44:46 GMT -5
There are two immune responses involved here: white blood cells attaching insulin producing cells and B-cells producing insulin antibodies. If a person is injecting insulin and the immune system can produce antibodies against insulin, these antibodies would have been created early. Is this legitimate or another impediment thrown in front of Afrezza? Are there documented cases of insulin antibodies?
4.4.6 Immunogenicity screencast.com/t/X6NR692m07bY
pg 135 of 248 www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM390864.pdf
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screencast.com/t/hec5DkuM6 pg 121 of 248
Immunogenic
Insulins, including Humulin R and Novolin R are labeled for allergic reactions, including severe, life-threatening, generalized allergy (e.g., anaphylaxis). Although human insulin and the insulin in Humulin R, Novolin R and Afrezza have identical amino acid sequences, expression systems in bacteria or yeast likely alter other characteristics of these products that predispose to allergy. Based on our knowledge of allergic reactions with currently available insulins, Afrezza TI is expected to have potential for hypersensitivity reactions. Potentially immune-related events were identified and summarized from a predefined set of MedDRA codes. This list of events was agreed upon with FDA prior to initiation of the two Gen2 phase 3 studies 171 and 175.
Table 31 summarizes adverse events potentially related to allergic reactions in the combined T1DM and T2DM population using the pre-specified MedDRA terms and using all available pooled phase 2/3 data as of the 2013 Resubmission. Similar to the original NDA event rates were low and generally comparable between Afrezza and comparator (which mostly included other insulin therapies): 2.4% (73/3017) in the Afrezza TI group, 1.5% (33/2198) in the comparator group, and 2.4% (7/290) in the TP group. Some of these adverse events (e.g., laryngospasm, throat tightness) may be related to a non-allergic mechanism (e.g., irritation) from inhalation of Afrezza.
Page 120 www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM390864.pdf
======================================================================================== pg 142 screencast.com/t/nAtncUZtMZ www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM390864.pdf
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Post by dreamboatcruise on Sept 14, 2015 20:45:13 GMT -5
I am surprised at the last primary measurement required in the trial and hence the reason for it lasting more than a year. "Measurement of anti-insulin antibodies [ Time Frame: Up to 13 months ] Designated as safety issue: Yes" Do some people create insulin antibodies? Yes they do. It was more of a concern with animal derived insulins but people do develop antibodies to human insulin. Some reports of actual insulin allergies... non of which have been associated with inhaled insulin. It was a point of concern regarding inhalation because the lungs are particularly immunologically active. It was originally theorized that it could pose a problem beyond injectable insulins because of this. Trials associated with Exubera and Afrezza showed slightly elevated levels of insulin-antibodies across the trial participants but still very low levels and no associated adverse outcomes or cases rising to level of insulin allergy. So the concern seems to have been put to bed with regard to adults... but apparently that is one area where there isn't 100% confidence a child's immune system would be the same. |
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Post by dreamboatcruise on Sept 14, 2015 20:57:57 GMT -5
That is a great question. Maybe that is part of the puzzle of why the pancreas gets attacked by the immune system. Maybe the doctors will chime in? Insulin antibodies are one of several tested for when T1 is suspected, so there is at least an association. Many T1's don't test positive for insulin antibodies so it isn't a necessary occurrence, but might be a contributing factor. I don't think medicine has a very good handle on the causal mechanism underlying most autoimmune disorders. Why do some peoples' bodies decide to attack themselves. I no longer have a thyroid because my body decided it didn't like it. |
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Post by Deleted on Sept 14, 2015 22:18:28 GMT -5
Peppy wrote
"Although human insulin and the insulin in Humulin R, Novolin R and Afrezza have identical amino acid sequences, expression systems in bacteria or yeast likely alter other characteristics of these products that predispose to allergy."
Got it. Thanks!
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Post by babaoriley on Sept 14, 2015 22:23:34 GMT -5
A doctor could prescribe Afrezza but probably would not for children. A 16 year old is still off label, but I think we have had some reports teenagers using Afrezza. I think I've seen some high school age kids using the Dreamboat, not sure about Afrezza, though. |
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Post by mssciguy on Sept 15, 2015 5:40:44 GMT -5
A doctor could prescribe Afrezza but probably would not for children. A 16 year old is still off label, but I think we have had some reports teenagers using Afrezza. I think I've seen some high school age kids using the Dreamboat, not sure about Afrezza, though. You mean ecigs, right? From what I know, they are not just for nicotine eliquids anymore. But it's a good point. The way those work has some similarities to dreamboat in terms of particle sizes (I know this from some consulting work). The ejuice is propylene glycol, glycerin, flavoring + active. There is no combustion, just a hot filament and some turbulence upon drawing, no significant vaporization-- it is an aerosol (why it looks like smoke) - and yes, a lot of different can be delivered in this way. But not insulin. Maybe some very short peptides but I don't know how efficiently or whether there would be some clogging. I'll tell you, what I could use some nights is Dreamboat plus en.wikipedia.org/wiki/Delta_sleep-inducing_peptide ... which seems to do a lot more than just produce sleep! |
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Post by oldfishtowner on Dec 10, 2015 21:14:39 GMT -5
Estimated Enrollment: 46 Study Start Date: August 2015 Estimated Study Completion Date: July 2017Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure) Hmm, is there a pediatric T2DM study as well? Edit - doh! this is only a Phase 1 study
Some thoughts on the pediatric study. Although the study completion date is give as August 2017, the protocol is only 6-8 weeks in duration. With only 46 patients, there is a good possibility that enrollment could be completed quickly. If so, it seems that data collection for the primary outcomes and all but one of the secondary outcomes could be completed by February or March? What I am thinking is that basically the trial results will be available for Sanofi to present to the FDA well before the August 2017 completion date. Another consideration is that Afrezza has already been proved as non-inferior. Maybe the phase 1 trial as a safety study in pediatric patients is all that is needed for the label extension. Does anyone know if this is possible? |
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Post by liane on Dec 10, 2015 21:28:40 GMT -5
The only roadblock I see is that in general, it's harder to recruit pediatric patients.
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Post by ricguy on Dec 10, 2015 21:36:28 GMT -5
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Post by mssciguy on Dec 10, 2015 21:41:32 GMT -5
The only roadblock I see is that in general, it's harder to recruit pediatric patients. Not sure, when I was a kid, nearly everything was covered by my father's union insurance (a rarity nowadays) but it was very easy to go to Marquette University for free dental care. Where they drilled the wrong tooth. Don't ever allow anyone you love to get free medical care. So,,,,, I see what you mean. |
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Post by Deleted on Dec 11, 2015 0:55:55 GMT -5
The only roadblock I see is that in general, it's harder to recruit pediatric patients. True, but in this case, needles vs no needles, and non compliance could cause parents to seek enrollment for their children. |
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Post by brad123 on Dec 11, 2015 2:39:50 GMT -5
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