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Post by mnholdem on Jun 7, 2018 12:09:31 GMT -5
While I was at the corporate website's pipeline page downloading the graphic, I branched out and did a little more exploration of the R&D webpages. This is an interesting little nugget I dug up:
Diverse Compatibility
Our dry powder formulation technology is compatible with a diverse assortment of drugs over a broad range of physicochemical characteristics, including molecular weight (300 – 150,000 Daltons), structure (small molecules to monoclonal antibodies), charge, and hydrophilicity/hydrophobicity. Our dry powders are ideally suited to deliver drugs for local diseases, such asthma and COPD.
In addition, the use of our Technosphere technology for systemic conditions was validated by the FDA approval of AFREZZA® (insulin human) inhalation powder, and has also been demonstrated in clinical studies with Technosphere formulations of parathyroid hormone (PTH/Technosphere), salmon calcitonin (sCT/Technosphere), and glucagon-like peptide 1 (GLP-1/Technosphere).
Source: www.mannkindcorp.com/research-development/tech-platforms/dry-powder-formulation/
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I wasn't aware that there were clinical studies conducted for these three API.
I few years ago I wrote that if Afrezza is a golden egg, then Technosphere is the goose that laid it. These studies bolster my opinion that, based on Intellectual Property alone, the stock market has greatly undervalued this company.
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Post by mnholdem on Jun 7, 2018 11:45:55 GMT -5
Mike said at ASM he wanted a partner for TrepT. Passing P 1 was probably a contigency of the term sheets he spoke of. Partner = cash non dilutive. Assume that a separate production line would be installed in Danbury for this product? How many different dosages would need to be made? Correct me if my memory is wrong: Existing product requires 8-12 daily doses from a large device and annual cost is around $125K. Lastly, is there some orphan status to this therapeutic class and if so, what are the ramifications? If I understand today's press release correctly, Trepostinil Technosphere can deliver larger doses than can be safely administered with Tyvaso. Larger doses could translate to fewer doses, but MannKind won't be able to elaborate on that until the Phase 3 PK Study is conducted to provide data on efficacy. An educated guess is that less doses will be needed daily with TreT than with the current treatments.
As far as your inquiry about orphan status, Trepostinil is not a new API so orphan would not be likely...or even needed, IMHO.
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Post by mnholdem on Jun 7, 2018 11:39:24 GMT -5
do I remember correctly that when trepT suddenly replaced epi , some thought that it was because it was easier to partner or sale and that we might already have someone waiting to see if the product was safe. So, now that we proved that the product is safe, what are the chances that we sale the right instead of waiting the end of the studies and how much could it worth at this point? I posted some thoughts on this some time ago. Based on the pipeline graphics at the corporate website, one could surmise that MannKind already has a partner in negotiations for TreT. As you can see from the pipeline graphic (below), it's clearly indicated that Epinephrine Technosphere and Palonosetron Technosphere are "AVAILABLE FOR LICENSE". Why wouldn't the Trepostinil say the same thing if MannKind didn't already have a partner for it?
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Post by mnholdem on Jun 7, 2018 11:24:06 GMT -5
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Post by mnholdem on Jun 7, 2018 8:15:31 GMT -5
Study achieved primary endpoint of safety and tolerability
- Progressive dosing of Treprostinil Technosphere (TreT) significantly exceeded the corresponding peak plasma and exposure levels of the maximum recommended dose of Tyvaso® Inhalation Solution
- Achieved a maximum tolerated dose with no serious adverse events reported
Source: investors.mannkindcorp.com/news-releases/news-release-details/mannkind-successfully-completes-phase-1-trial-treprostinil
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"Significantly exceeded" maximum recommended dose of Tyvaso® Inhalation Solution. It appears that MannKind CMO David Kendall MD understands the value of publishing comparisons against the competition.
“We are excited to utilize our existing technology platform and device capabilities to create an easy-to-use and tolerable formulation of treprostinil to help unmet patient needs in a serious chronic disease such as PAH.” - David Kendall, Chief Medical Officer of MannKind
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Post by mnholdem on Jun 7, 2018 8:10:51 GMT -5
Where is sla55 and what have you done with her?  |
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Post by mnholdem on Jun 7, 2018 7:31:15 GMT -5
So what's the difference between the Estimated Primary Completion Date and the Estimated Study Completion Date? And don't tell me one year ;-) The first is the date by which clinical trial data related to the Primary Outcome Measures will be collected for analysis. By the Study Completion Date, clinical trial data related to all the remaining Secondary Outcome Measures will be ready for analysis. |
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Post by mnholdem on Jun 7, 2018 7:27:41 GMT -5
The Primary Outcome: Hemoglobin A1c [3-month between-group change in A1c assessed by a central lab] on track to be completed by 4th Quarter 2018.
There has been a fairly robust debate among ProBoards-MNKD members about endocrinologists and PCP's currently using A1c as the standard measurement to assess patients with diabetes mellitus. As the adoption and acceptance of Continuous Glucose Monitoring (CGM) among the diabetes medical community grows, new measurement standards will be forthcoming.
"A majority of the speakers were excited about the progress being made in standardizing glycemic outcomes beyond A1c, such as defining the blood glucose ranges associated with time-in-range (and out-of-range), instances of hypoglycemia or hyperglycemia, and other metrics related to CGM." - July 22, 2017 report of the “Glycemic Outcomes Beyond A1c: Standardization and Implementation” gathering of leaders in the diabetes community. diatribe.org/measuringwhatmatters
Science is rapidly progressing and, with CGM and other new technologies ushering in a new age for better control of diabetes, new measurement standards will be adopted by the diabetes community. Still, A1c remains the predominant measurement by which endocrinologists, primary care physicians and other healthcare professional measure the health of patients with diabetes mellitus.
The A-ONE trial will present data on both the current A1c standard of measurement (arguably adhered to by most HCPs) and future standards of measurement and provide empirical evidence on the health benefits of Afrezza inhaled insulin, focusing on effective treatment and quality of life issues for patients with Type 2 diabetes.
The science will prevail.
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Post by mnholdem on Jun 7, 2018 6:54:15 GMT -5
Source: clinicaltrials.gov/ct2/show/NCT03313960?term=MANNKIND&recrs=abdfg&rank=4
ClinicalTrials.gov Identifier: NCT03313960
Recruitment Status : Active, not recruiting
First Posted : October 19, 2017
Last Update Posted : June 1, 2018
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Study Design
Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A-One: A Randomized Controlled Trial Evaluating One Drop | Premium With Afrezza vs. One Drop | Premium Alone
Actual Study Start Date: October 5, 2017
Estimated Primary Completion Date: September 30, 2018
Estimated Study Completion Date: September 30, 2019
Primary Outcome Measures
- Hemoglobin A1c [ Time Frame: 3 months ]
Secondary Outcome Measures
- Insulin Device Satisfaction [ Time Frame: 3 months ] assessed by the Insulin Device Satisfaction Survey (IDSS);
- Treatment Adherence [ Time Frame: 3 months ] assessed by ARMS-D*, SDSCA-MS* and SDSCA-IS*;
- Self-care [ Time Frame: 3 months ] assessed by the SDSCA's other subscales;
- Health-related Productivity [ Time Frame: 3 months ] assessed by the Work Productivity and Activity Impairment measure (WPAI);
- Health-related Quality of Life [ Time Frame: 3 months ] assessed by CDC HRQOL-14* and the Cantril Self-Anchoring Ladder of Life Satisfaction.
*Acronyms
ARMS-D = Adherence to Refills and Medications Scale for Diabetes SDSCA-MS = Summary of Diabetes Self-care Activities Medications Subscale administered for each oral diabetes medication SDSCA-IS = Summary of Diabetes Self-care Activities Medications Subscale administered for insulin in the regimen
CDC HRQOL-14 = Centers for Disease Control Health-related Quality of Life-14
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Post by mnholdem on Jun 6, 2018 13:02:11 GMT -5
Jeez, you guys are on a roll today! |
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Post by mnholdem on Jun 6, 2018 12:57:24 GMT -5
I am assuming some of the buyers @$6 never shorted. If traders bought in on what amounted to a brief 3-5 day spike, hoping to make a quick buck, then they deserve what they got. The more prudent investors were actually selling a percentage of their positions when MNKD pps reached the $6 level and are now playing with free money if they re-invested their gains.
It amazes me sometimes how traders like to blame the company for those losses rather than acknowledging their own stupidity.
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Post by mnholdem on Jun 6, 2018 12:45:44 GMT -5
"...intensive therapy was associated with a high rate of severe hypoglycemia (61 episodes per 100 patient- years of therapy). Since the DCCT, a number of rapid-acting and long-acting insulin analogs have been developed. These analogs are associated with less hypoglycemia, less weight gain, and lower A1C than human insulins in people with type 1 diabetes..."
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Diabetes Control and Complications Trial (DCCT)
DCCT Results
The DCCT showed that people with type 1 diabetes who kept their blood glucose levels as close to normal as safely possible with intensive diabetes treatment as early as possible in their disease had fewer diabetes-related health problems after 6.5 years, compared to people who used the conventional treatment.
DCCT showed that people who used intensive treatment lowered their risk of
- diabetic eye disease by 76 percent; and advancement of eye disease by about half (54 percent), in people with some eye disease at the beginning of the study.
- diabetic kidney disease by 50 percent.
- diabetic nerve disease by 60 percent.
Researchers were not able to show whether people who used intensive treatment lowered their risk of heart disease during the DCCT, since only a few people had heart disease during the study.
Participants who used intensive treatment had an average A1C of 7 percent, while participants who used the conventional treatment had an average A1C of 9 percent. The A1C blood test shows a person’s average blood glucose levels over the previous 2 to 3 months. A normal A1C value is 6 percent or less.
In the DCCT, the major side effect of intensive treatment was a higher risk for hypoglycemia, also called low blood glucose, which can be deadly if not treated immediately. Participants knew how to treat hypoglycemia.
The Diabetes Control and Complications Trial (DCCT) took place from 1983 to 1993. The study involved 1,441 volunteers ages 13 to 39, and took place in 29 medical centers in the United States and Canada. At the start of the DCCT, participants had type 1 diabetes for at least 1 year but no longer than 15 years, and had no or only early signs of diabetic eye or kidney diseases.
Source: www.niddk.nih.gov/about-niddk/research-areas/diabetes/blood-glucose-control-studies-type-1-diabetes-dcct-edic
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The fact that the ADA Standard of Care for Diabetes references the hypoglycemic dangers of intensive insulin therapy based on a study that is more than 30 years old is a excellent example of how out-of-touch the American Diabetes Association is in their recommendations of diabetes treatments. They do acknowledge that since DCCT rapid-acting analogs have been developed which are associated with less hypoglycemia but, of course, there is no mention of ultra-rapid acting inhaled insulin, which is NOT an analog insulin and is much faster with less hypoglycemic risk.
IMHO, MannKind's CMO David Kendall MD is correct in his assessment that current practices for treating diabetes are antiquated and barbaric.
Is it any wonder that diabetes is currently the most costly disease in the USA?
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Post by mnholdem on Jun 5, 2018 9:59:10 GMT -5
The counter to that is going to be that it was achieved at the cost of a worse HbA1c outcome and that if the RAA arm had similarly underperformed their hypo rate would also be lower. That said I don't see a poster having a lot of impact, they need to get this published in a journal. 100% agree with getting the data published, but I don't see how you can assume a worse HbA1c outcome unless you see all the data. It's quite possible that the analysis filtered out doses taken too soon before mealtime, for example. We'll all have to wait to see what they Kendall and the SAB did with the data, I think. |
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Post by mnholdem on Jun 5, 2018 6:51:10 GMT -5
So we have the huge nebulizer that seems to have never started clinical trials, and liquidia which is ahead of mnkd and could be just as effective as the mnkd drug. Sounds like we could be a few years late. Nope. The MannKind trepostinil Phase 1 trial will be completed December 2018 and the Phase 3 has been estimated by CMO David Kendall MD to be complete in late 2019, which puts it slightly ahead of Liquidia's, whose clinical trial for LIQ861 has an estimated study completion date of July 2020.
MannKind anticipates filing its NDA by mid-2020 while Liquidia will only have just completed its safety study. Also, the LIQ861 has only one Primary Outcome related to adverse events and seriously adverse events. MannKind's will have a full PK study data completed in 2019.
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Post by mnholdem on Jun 5, 2018 3:37:45 GMT -5
Thanks, brotherm1.
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