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Post by lakers on Jan 25, 2016 22:44:33 GMT -5
Subject: Is it too late to join Afrezza pediatric study? Hi Bao-khanh, Regarding the Afrezza pediatric study, have you finished recruiting and started trial for Phase one yet? When will Phase 1 finish? When will Phase 2 start and finish? What dosing at what time do you expect? For example do you need more Afrezza units per unit of basal drug? Do you inhale 10 mins after starting a meal? What CGM do you use? If it's not too late, I can refer my relative to join the trial. Now that Sanofi terminates partnership with Mannkind, who gonna manage and fund Phase 1 and 2? Thanks, RE: Is it too late to join Afrezza pediatric study? Reply at 4:13 PM 1/25/16 I apologize for the delay in response. Those definitely good question. We are still currently still recruiting for our cohort I (ages 13-17). As far as starting for cohort II (ages 8-12) that is dependent on the data that we have collected for our cohort I. As far as dosing, it depends on the child's carb to insulin ratio. Currently Afrezza's insulin dosing is equivalent to that of the rapid acting insulin drug 1:1 ratio of how you would usually dose with your rapid/short-acting insulin. As far as basal, the dosing should not change when enrolled in the study. For the CGM, the model that is being used is the G4 however the data will be blinded therefore the child will not be able to see the data on the CGM. As far as the partnership study will still continue its course for recruitment. We are always happy to answer any questions you or your relative may have. Thank you for your interest in our study! Sincerely, Bao-Khanh Tran, BS Professional Research Assistant for Dr. Wadwa Barbara Davis Center for Childhood Diabetes University of Colorado School of Medicine Mail Stop F527 1775 Aurora Court Aurora, CO 80045 Phone: 303-724-8095 bao-khanh.tran@ucdenver.edu clinicaltrials.gov/ct2/show/NCT02527265?term=439065&rank=2 |
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Post by 4allthemarbles on Jan 25, 2016 23:39:30 GMT -5
So, forgive the question- but why didn't SFY just pull the plug on this? Also, how is this funded?
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Post by Deleted on Jan 25, 2016 23:44:42 GMT -5
Subject: Is it too late to join Afrezza pediatric study? Hi Bao-khanh, Regarding the Afrezza pediatric study, have you finished recruiting and started trial for Phase one yet? When will Phase 1 finish? When will Phase 2 start and finish? What dosing at what time do you expect? For example do you need more Afrezza units per unit of basal drug? Do you inhale 10 mins after starting a meal? What CGM do you use? If it's not too late, I can refer my relative to join the trial. Now that Sanofi terminates partnership with Mannkind, who gonna manage and fund Phase 1 and 2? Thanks, RE: Is it too late to join Afrezza pediatric study? Reply at 4:13 PM 1/25/16 I apologize for the delay in response. Those definitely good question. We are still currently still recruiting for our cohort I (ages 13-17). As far as starting for cohort II (ages 8-12) that is dependent on the data that we have collected for our cohort I. As far as dosing, it depends on the child's carb to insulin ratio. Currently Afrezza's insulin dosing is equivalent to that of the rapid acting insulin drug 1:1 ratio of how you would usually dose with your rapid/short-acting insulin. As far as basal, the dosing should not change when enrolled in the study. For the CGM, the model that is being used is the G4 however the data will be blinded therefore the child will not be able to see the data on the CGM. As far as the partnership study will still continue its course for recruitment. We are always happy to answer any questions you or your relative may have. Thank you for your interest in our study! Sincerely, Bao-Khanh Tran, BS Professional Research Assistant for Dr. Wadwa Barbara Davis Center for Childhood Diabetes University of Colorado School of Medicine Mail Stop F527 1775 Aurora Court Aurora, CO 80045 Phone: 303-724-8095 bao-khanh.tran@ucdenver.edu clinicaltrials.gov/ct2/show/NCT02527265?term=439065&rank=2they still dont get it? some times its always not 1:1 hopefully they dont dose at the same time as injectable - that would be a disaster |
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Post by Deleted on Jan 25, 2016 23:44:40 GMT -5
Damage control is why they havent pulled the plug
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Post by suebeeee1 on Jan 25, 2016 23:49:07 GMT -5
Q. Now that Sanofi terminates partnership with Mannkind, who gonna manage and fund Phase 1 and 2?
A. As far as the partnership study will still continue its course for recruitment.
It does not seem to me that Bao-Khanh Tran answered the partnership question directly, but rather simply stated that the study would go on.
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Post by Deleted on Jan 25, 2016 23:49:29 GMT -5
Damage control is why they havent pulled the plug Sanofi will continue until april 4 and then all the cost gets transferred to Mannkind. |
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Post by dreamboatcruise on Jan 26, 2016 0:27:34 GMT -5
Well, that's a bummer. When the initial details of the study were revealed some of us, including myself, were excited about CGM being mentioned... thinking erroneously that they might use the CGM to get optimal dosing and between meal corrections that might allow this pediatric study to be one with a superiority outcome. Sadly, CGM will not be used to dial in dosing and corrections. That study would then still be a ways off.
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Post by esstan2001 on Jan 26, 2016 1:23:31 GMT -5
Well, that's a bummer. When the initial details of the study were revealed some of us, including myself, were excited about CGM being mentioned... thinking erroneously that they might use the CGM to get optimal dosing and between meal corrections that might allow this pediatric study to be one with a superiority outcome. Sadly, CGM will not be used to dial in dosing and corrections. That study would then still be a ways off. Sanofi developed the protocol? Mannkind left holding the bag to finish up? They should at least be able to discuss amending the protocol with the FDA before it commences. Or run another arm of the study with CGM dosing feedback. Then try that with injectable- ha! that would show'em. |
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Post by mnholdem on Jan 26, 2016 6:29:40 GMT -5
I believe that MannKind's part of the expenses can still be applied to the Sanofi loan facility. After the termination date, MannKind would be responsible for 100% of the costs for the trail, which is expected to involve approximately 42 patients, but I'll have to read the fine print of the agreement to determine whether the loan can still be used. If so, then Sanofi must continue to loan MannKind up to $175 million for continuing development of Afrezza, enable MannKind to protect its cash on hand.
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Post by matt on Jan 26, 2016 9:23:28 GMT -5
I don't think the Sanofi loan facility is available after April 4. If you read the documents carefully, and I have, the only possible use for the Sanofi loan facility is to absorb the loss share of the partnership incurred by Mannkind (i.e. their 35% of losses). When the partnership officially ends on April 4, so do the partnership losses. At that point Mannkind's share of the partnership loss is $0 so the amount they can fund via the loan facility is also $0. Sanofi has to fund Mannkind's expenses through April 4, but as of April 5 Mannkind is on their own for 100% of the costs.
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Post by agedhippie on Jan 26, 2016 10:04:07 GMT -5
they still dont get it? some times its always not 1:1 hopefully they dont dose at the same time as injectable - that would be a disaster If by injectable you mean their basal then there is no issue. The only meal time insulin they are taking is Afrezza. The 1:1 ratio is the starting point, there is an expectation with these trials that this is fine tuned as the trial progresses which is why there is often a run-in phase. |
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Post by dreamboatcruise on Jan 26, 2016 11:47:25 GMT -5
Well, that's a bummer. When the initial details of the study were revealed some of us, including myself, were excited about CGM being mentioned... thinking erroneously that they might use the CGM to get optimal dosing and between meal corrections that might allow this pediatric study to be one with a superiority outcome. Sadly, CGM will not be used to dial in dosing and corrections. That study would then still be a ways off. Sanofi developed the protocol? Mannkind left holding the bag to finish up? They should at least be able to discuss amending the protocol with the FDA before it commences. Or run another arm of the study with CGM dosing feedback. Then try that with injectable- ha! that would show'em. I guess it was a bit of wishful thinking on my part. Looking at it, it is logical that there is no way to have a blinded comparison study if people have meter feedback and instructions to titrate (it would be criminal to have drugs blinded and give the same titration instructions... I assume in blinded they are both injecting and inhaling with one being placebo depending on which arm they are in, so you could tell people to does again 1 hr after if they are rising or you'd kill the participants in the SQ RAA arm). I'm sure the FDA required a basic blinded study to show that the results in pediatric patients were the same as the adult results. The type of study using the CGM for feedback to show superiority would have to be in addition to the basic one required. At that point it becomes questionable whether doing it as part of the pediatric study would have any merit vs simply doing it separately with all ages involved. It's amazing how easy it is to overlook reality (what we should know the FDA requires) in order to engage in wishful thinking, such as I did on hearing CGMs were involved in pediatric... I'm trying to learn lessons from past mistakes. The one thing we can still hope is that perhaps they clear up the dosing timing issue. If I'm correct about how they are blinding this test, they could still have each delivery route used at the appropriate time for its active ingrediant... injection 15 min before meal and inhale after start of meal. Hopefully. Though, perhaps the FDA really would want apples to apples to replicate adult trial. |
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Post by mnholdem on Jan 26, 2016 11:50:39 GMT -5
I don't think the Sanofi loan facility is available after April 4. If you read the documents carefully, and I have, the only possible use for the Sanofi loan facility is to absorb the loss share of the partnership incurred by Mannkind (i.e. their 35% of losses). When the partnership officially ends on April 4, so do the partnership losses. At that point Mannkind's share of the partnership loss is $0 so the amount they can fund via the loan facility is also $0. Sanofi has to fund Mannkind's expenses through April 4, but as of April 5 Mannkind is on their own for 100% of the costs. I still haven't found anything which specifically prevents MannKind from continuing to borrow from Aventisub LLC. I have thoroughly read through the Loan Facility Agreement and determined that MannKind's costs associated with Afrezza may continue to be covered advancement via the Loan Agreement until there is a Default (and Termination of Agreement is NOT considered a default).
Like it or not, Sanofi set up the Loan Facility for MannKind to use up to $175 Million to cover expenses related to marketing and developing Afrezza. Since the Loan Facility is a separate instrument from the License & Collaboration Agreement, MannKind Corporation may be able to still borrow against it just like any other Line-of-Credit, provided that advancements do not exceed Afrezza expenses (per the Agreement). That means, of course, that MannKind would need to disclose the numbers to Sanofi. Also, the provision that any profit generated from future sales of Afrezza must still FIRST be used as payments to pay back Aventisub LLC (the lender), would also remain intact.
However, as long as the Loan has not been paid in full, Sanofi retains vitually everything Afrezza-related, as collateral against the loan. I would think that MannKind would seek to pay back the $45 Million borrowed thus far, and do it as soon as possible. Regardless, it will be very interesting to see what details come out as the transitional period unfolds. Will Sanofi forgive the $45M debt in exchange for certain assurances? Stay tuned... (now where did I hear that phrase?)   
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Post by chuck on Jan 26, 2016 12:27:57 GMT -5
This is very simple. Section 2.1 only allows MNKD to borrow once a quarter in an amount up to mnkd's 35% share of losses under the partnership agreement for the previous quarter. When the partnership agreement is cancelled in April, there will be no quarterly loss under the partnership agreement for future periods and therefore mnkd can't borrow anything further. Matt is correct.
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Post by esstan2001 on Jan 26, 2016 12:30:04 GMT -5
... At that point it becomes questionable whether doing it as part of the pediatric study would have any merit vs simply doing it separately with all ages involved. It's amazing how easy it is to overlook reality (what we should know the FDA requires) in order to engage in wishful thinking, such as I did on hearing CGMs were involved in pediatric... I'm trying to learn lessons from past mistakes. The one thing we can still hope is that perhaps they clear up the dosing timing issue. If I'm correct about how they are blinding this test, they could still have each delivery route used at the appropriate time for its active ingrediant... injection 15 min before meal and inhale after start of meal. Hopefully. Though, perhaps the FDA really would want apples to apples to replicate adult trial. The reason I'd like to see another arm added to the study (I assume it has to stay pediatric, as it is titled as such) that could show superiority, is time.
To at least be able to claim superiority for kids by some time later this year, I think many PWD would assume hey, if it works better for kids, why wouldn't it also work better for adults... An adult superiority study is another study, more money, and has to get through the whole process (more time). Pedi is almost ready to run. I'd take a 2-3 month delay to get some superiority test into the trial. To me the faster we can make any better (even incrementally so) claims on the label, the sooner the fog lifts. |
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