|
Post by biotec on Apr 2, 2014 7:53:49 GMT -5
With such a overwhelmed vote, how can the FDA reject us? Is anyone concerned about this?
|
|
|
Post by jpg on Apr 2, 2014 12:01:18 GMT -5
The FDA could theoretically still reject but the medical politics involved would be career suicide for who dared to do that.
I read the same adcom blog as all of you and didn't listen in but if the tone was well conveyed, and I believe it was, the FDA was barely there. You had a group of very respected MDs who represent the who's who of the medical establishment and some influential diabetic patient advocates pushing hard for this to move forward. Again I wasn't there or listening in but from what I know of scientific interaction there seemed to have been almost disdain for the scientific evaluation and understanding of diabetic management and even basic science at some points. I had the same feeling when going through the documents. I kept on thinking this was evaluated by inexperienced staffers to be polite. The panel of experienced clinicians seemed to react the way I was hoping them to react anyway.
All this to say I think yesterday was the big hurdle.
|
|
|
Post by BD on Apr 2, 2014 14:07:03 GMT -5
It does feel like that was the big hurdle. And just as it was important not to read too much into PPS movement for the weeks prior to Ad-Comm, I think it's even less useful to worry about what the PPS is doing today or what it does between now and a partnership announcement.
If anyone should be worried about the price movement at this point, it would be the shorts.
|
|
|
Post by esstan2001 on Apr 3, 2014 7:41:41 GMT -5
By plcfischer in comments section of Brian Orelli MF article this AM: this captures what AL has been trying to convey for all these years and what the FDA seems dense as wood about regarding Afrezza-
The FDA fell into the HbA1c trap. What is the HbA1c (A1c) trap? It is the trap that is created when a proxy measure (A1c) is treated as more important than the direct measurement (plasma glucose). This is very easy to do with diabetes treatment. A1c is a measure of average plasma glucose over three months. A direct plasma glucose measurement shows a point in time. Because plasma glucose changes rapidly, point in time measurements are not very useful in the clinic. Because in a clinical environment A1c is the better measurement the American Diabetes Association (ADA) and other professional societies use A1c in their treatment guide lines.
The FDA, using well established methods used A1c as a measure of how well Afrezza worked to treat diabetes. The problem is they took it to far, way to far. Looking on page 50 of the briefing document you will see where the FDA is stating that the superior reduction in Fasting Plasma Glucose (FPG) in the Afrezza arm is due to the increase in basal insulin used in that arm. I have no argument with that statement, but it is incomplete. I will argue that the increase in basal insulin is made possible because Afrezza is better for glucose control than the current prandial (meal time) insulins. If you look on page 55 you will find more evidence that Afrezza is not an effective basal insulin, nor is it intended to be. Afrezza did not have a significant effect on FPG when not taken with treatments that cause a decrease in FPG. This should have been expected. Looking on pages 90 and 91, you will find evidence of Afrezza's superior glucose control in preventing hypoglycemia. Afrezza patients had less than half of the hypoglycemic events where blood glucose dropped below 37 mg/dL compared to current prandial insulin patients. As would be expected your Afrezza patients did have more hypoglycemic events than placebo patients.
For my theory to work, Afrezza patients must have no more hyperglycemia than current treatments. Looking on page 67 you will find that the rate is the same. On page 72 you will find that Afrezza is superior versus placebo (as expected).
In conclusion, I find that the FDA's assertion that Afrezza's patients took more basal insulin or other treatments to lower A1c to be true. But unlike the FDA, I consider this to be a positive. The evidence is strong that the ultra fast action of Afrezza lowers the excursion of blood glucose levels better than current prandial treatments. This lowering of excursions allows for more aggressive treatments for lowering A1c without an increased risk for hypoglycemia. The FDA got it wrong, but the panel got it right. Lets hope for the sake of diabetes patients and for our retirement accounts that the FDA sees the light and follows the panel's advice.
|
|
|
Post by spiro on Apr 3, 2014 7:47:55 GMT -5
Interesting post on YMB yesterday.
broad_and_south • Apr 2, 2014 8:20 AM
Successful AdCom I was at the AdCom yesterday and can tell you it was a breathtaking experience. The ebb and flow was palpable and in the end, the good guys won.
The FDA team was visibly depressed at the end. They were so wrapped up in statistics and digging for dirt that they wholly lost sight of the larger picture. The users and doctors told the FDA there is a need for a delivery method for insulin that is not subcutaneous injection. The existing tools to enable diabetics to control their blood sugar are woefully inadequate. Patients fear dying or losing their sight and there is not much they can do about it. Afrezza’s fast acting pharmacokinetics is a much-needed product. The entire AdCom could have been avoided if the FDA had called physician thought leaders and diabetic care groups for their input.
The first sign that the battle was not going to be one sided was when the Committee’s statistician Brittian first spoke. I thought she was going to dive into the biostatistics with the FDA and agree with them that the 171 study was marginal. To my surprise, she said the results were marginal but perhaps the FDA placed too high a non-inferiority standard. She ultimately proved to be an advocate. She got the bigger picture.
Strange fact: the industry representative Mats Rasmussen did not contribute anything to the meeting. Maybe NOVO is negotiating now with Al?
The Committee imposed several pulmonary conditions on the label. I think this will delay PDUFA but not by months.
The FDA has final say and they can issue another CRL. But that is saying they know more than the AdCom presenters. This will not happen. It was like Seattle beating Denver in the Superbowl. Less
|
|
|
Post by mannmade on Apr 3, 2014 9:20:14 GMT -5
esstan, the last paragraph of your post is exactly the whole point for afrezza. Yes the FDA and a whole lot of doctors have this wrong... totally agree just wonder why so hard to see... Not to mention the quality of life upgrade it gives diabetics... Have aways wondered why no real concern about quality of life...
|
|
|
Post by BD on Apr 3, 2014 10:26:32 GMT -5
So, if the FDA pushes back the PDUFA date, when would they typically be announcing that? How 11th-hour could a delay possibly be?
|
|
|
Post by liane on Apr 3, 2014 10:33:01 GMT -5
It can be very 11th hour, or even 12th hour.
|
|
|
Post by brentie on Apr 3, 2014 10:39:44 GMT -5
|
|
|
Post by BD on Apr 3, 2014 10:40:54 GMT -5
Geez.
|
|
|
Post by chmith27 on Apr 3, 2014 10:55:02 GMT -5
By plcfischer in comments section of Brian Orelli MF article this AM: this captures what AL has been trying to convey for all these years and what the FDA seems dense as wood about regarding Afrezza- The FDA fell into the HbA1c trap. What is the HbA1c (A1c) trap? It is the trap that is created when a proxy measure (A1c) is treated as more important than the direct measurement (plasma glucose). This is very easy to do with diabetes treatment. A1c is a measure of average plasma glucose over three months. A direct plasma glucose measurement shows a point in time. Because plasma glucose changes rapidly, point in time measurements are not very useful in the clinic. Because in a clinical environment A1c is the better measurement the American Diabetes Association (ADA) and other professional societies use A1c in their treatment guide lines. The FDA, using well established methods used A1c as a measure of how well Afrezza worked to treat diabetes. The problem is they took it to far, way to far. Looking on page 50 of the briefing document you will see where the FDA is stating that the superior reduction in Fasting Plasma Glucose (FPG) in the Afrezza arm is due to the increase in basal insulin used in that arm. I have no argument with that statement, but it is incomplete. I will argue that the increase in basal insulin is made possible because Afrezza is better for glucose control than the current prandial (meal time) insulins. If you look on page 55 you will find more evidence that Afrezza is not an effective basal insulin, nor is it intended to be. Afrezza did not have a significant effect on FPG when not taken with treatments that cause a decrease in FPG. This should have been expected. Looking on pages 90 and 91, you will find evidence of Afrezza's superior glucose control in preventing hypoglycemia. Afrezza patients had less than half of the hypoglycemic events where blood glucose dropped below 37 mg/dL compared to current prandial insulin patients. As would be expected your Afrezza patients did have more hypoglycemic events than placebo patients. For my theory to work, Afrezza patients must have no more hyperglycemia than current treatments. Looking on page 67 you will find that the rate is the same. On page 72 you will find that Afrezza is superior versus placebo (as expected). In conclusion, I find that the FDA's assertion that Afrezza's patients took more basal insulin or other treatments to lower A1c to be true. But unlike the FDA, I consider this to be a positive. The evidence is strong that the ultra fast action of Afrezza lowers the excursion of blood glucose levels better than current prandial treatments. This lowering of excursions allows for more aggressive treatments for lowering A1c without an increased risk for hypoglycemia. The FDA got it wrong, but the panel got it right. Lets hope for the sake of diabetes patients and for our retirement accounts that the FDA sees the light and follows the panel's advice. esstan, very well put
|
|
|
Post by typeonedad on Apr 3, 2014 13:00:22 GMT -5
Esstan, so exactly on point. The point of prandial insulin to cover the meal and the meal only. The reality for type-1's is that when you bolus Humolog or Novalog at mealtime, it adds to the existing insulin in the system that is meant to be "basal" insulin. So there is a layering affect of existing insulin meant to be basal, with the tail of the bolused insulin from a prior meal. This creates the havoc for type 1's or parents of type 1's. Afrezza is going to isolate the mealtime insulin need, leaving basal insulin to do its thing, keeping the body steady for the other 20 hours of the day.
Diabetics, their parents and their endo's are going to be able to be more aggresive, more accurate with both the basal and bolus insulin regiment because the two issues will be more clearly separated. This could very well mean more basal insulin. So what! With improved regiments, I believe A1c's will go down once this great new tool, Afrezza is fully incorporated. And more important than that, the highs will be less high and the lows will be less low. Parents of type 1's such as myself are terrified of lows (death) and back of the mind worried about ongoing highs. DKA yes, but more so, the long term affects on the body (life expectancy) of continously running high. An A1c of 8 with limited excursions above 250 or below 70 will-be-life-changing.
There are so many brillant people this board who interpret the data, report objectively, and cut through the marketplace B.S.....I am extremely grateful.
|
|
|
Post by notamnkdmillionaire on Apr 3, 2014 13:45:33 GMT -5
Esstan, so exactly on point. The point of prandial insulin to cover the meal and the meal only. The reality for type-1's is that when you bolus Humolog or Novalog at mealtime, it adds to the existing insulin in the system that is meant to be "basal" insulin. So there is a layering affect of existing insulin meant to be basal, with the tail of the bolused insulin from a prior meal. This creates the havoc for type 1's or parents of type 1's. Afrezza is going to isolate the mealtime insulin need, leaving basal insulin to do its thing, keeping the body steady for the other 20 hours of the day. Diabetics, their parents and their endo's are going to be able to be more aggresive, more accurate with both the basal and bolus insulin regiment because the two issues will be more clearly separated. This could very well mean more basal insulin. So what! With improved regiments, I believe A1c's will go down once this great new tool, Afrezza is fully incorporated. And more important than that, the highs will be less high and the lows will be less low. Parents of type 1's such as myself are terrified of lows (death) and back of the mind worried about ongoing highs. DKA yes, but more so, the long term affects on the body (life expectancy) of continously running high. An A1c of 8 with limited excursions above 250 or below 70 will-be-life-changing. There are so many brillant people this board who interpret the data, report objectively, and cut through the marketplace B.S.....I am extremely grateful. What's sad is that the doctors on the Adcom and those dolt government fools at the FDA can't seem to comprehend this.
|
|
|
Post by esstan2001 on Apr 3, 2014 14:01:02 GMT -5
The point of prandial insulin to cover the meal only... when you bolus at mealtime, it adds to the existing insulin in the system that is meant to be "basal" insulin. So there is a layering affect of existing ... basal, with the tail of the bolused insulin from a prior meal. This [stacking] creates the havoc for type 1's or parents of type 1's. Afrezza is going to isolate the mealtime insulin need, leaving basal insulin to do its thing, keeping the body steady for the other 20 hours of the day. Diabetics, their parents and their endo's are going to be able to be more aggresive, more accurate with both the basal and bolus insulin regiment because the two issues will be more clearly separated. This could very well mean more basal insulin. ...more important than that, the highs will be less high and the lows will be less low. Parents of type 1's such as myself are terrified of lows (death) and back of the mind worried about ongoing highs. DKA yes, but more so, the long term affects on the body (life expectancy) of continuously running high. An A1c of 8 with limited excursions above 250 or below 70 will-be-life-changing.typeonedad- count yourself among the so many brilliant people on this board: IMO your statement above is the clearest, most succinct, almost 'soundbite like' reason advocating for Afrezza. This should be sent to Mannkind and used everywhere as their clarion call to the FDA for approval.
|
|
|
Post by typeonedad on Apr 3, 2014 14:27:09 GMT -5
Biotec, that means a lot coming from you. I am long overdue to make some kind of contribution to this board, all taking no giving. Any comments from me will no doubt be 8th grade reading level because that's about as high as I can elevate! I have a rounded understanding of type 1, grounded in day to day management. Once the science gets past the opening paragraph I begin to strain!
I have a 13 year old son diagnosed at 5, pump therapy for the last 7 years. My wife and I would not likely not consider Afrezza while he is a growing teen. But the idea that he may be able to head off to college with an extremly hypo resistent therapy regiman...a therapy with a 4 or 5 year track record by 2019....gives me shivers of relief.
|
|