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Post by rockstarrick on Jul 7, 2016 15:52:35 GMT -5
Can this study be used for updating the label ?? Beginning not later than 18 months after approval, scientists from the Office of Surveillance and Epidemiology and Office of New Drugs in the Center for Drug Evaluation and Research (CDER) jointly review the relevant data, summarize findings and, when necessary, develop a plan to further investigate potential new safety issues for products regulated by CDER. For medical products regulated by the Center for Biologics Evaluation and Research, this safety review and evaluation is conducted by scientists from CBER's Office of Biostatistics and Epidemiology and the relevant product office (Office of Blood Research and Review, Office of Vaccine Research and Review, or Office of Cellular, Tissue and Gene Therapies). FDA compiles the postmarket safety evaluations and periodically posts the summary reports on this website. For additional information about postmarket drug and biologic safety issues, including FDA Safety Communications and web postings of Potential Signals of Serious Risks Identified from the FDA Adverse Event Reporting System (FAERS), please refer to FDA's website on Postmarket Drug Safety Information for Patients and Providers or Safety and Availability (Biologics). www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/ucm204091.htm |
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Post by twiddledee on Jul 9, 2016 20:08:30 GMT -5
From the FDA briefing document, it doesn't appear so:
"However, to evaluate the long-term risk of lung cancer, a postmarketing observational cohort trial is planned. The primary objective of the study will be to determine the incidence of primary pulmonary malignancies in patients taking TI. Secondary objectives will be to determine the incidence of all other malignancies (except non-melanoma skin cancers), serious pulmonary events, serious allergic events, and serious hypoglycemic events. Approximately 1,800 patients will be enrolled and followed for at least 5 years(approximately 8,000 person-years of follow-up exposure). Enrolled patients will be followed for the duration of the study or until withdrawal from participation or death."
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Post by rockstarrick on Jul 10, 2016 10:46:30 GMT -5
From the FDA briefing document, it doesn't appear so: "However, to evaluate the long-term risk of lung cancer, a postmarketing observational cohort trial is planned. The primary objective of the study will be to determine the incidence of primary pulmonary malignancies in patients taking TI. Secondary objectives will be to determine the incidence of all other malignancies (except non-melanoma skin cancers), serious pulmonary events, serious allergic events, and serious hypoglycemic events. Approximately 1,800 patients will be enrolled and followed for at least 5 years(approximately 8,000 person-years of follow-up exposure). Enrolled patients will be followed for the duration of the study or until withdrawal from participation or death." Lol, I found Fragslap,,, this must be a sore subject. Thanks Slappy, I'll continue to wait for our member "Matt" to comment. As always Good Luck Rock |
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Post by peppy on Jul 10, 2016 21:12:52 GMT -5
From the FDA briefing document, it doesn't appear so: "However, to evaluate the long-term risk of lung cancer, a postmarketing observational cohort trial is planned. The primary objective of the study will be to determine the incidence of primary pulmonary malignancies in patients taking TI. Secondary objectives will be to determine the incidence of all other malignancies (except non-melanoma skin cancers), serious pulmonary events, serious allergic events, and serious hypoglycemic events. Approximately 1,800 patients will be enrolled and followed for at least 5 years(approximately 8,000 person-years of follow-up exposure). Enrolled patients will be followed for the duration of the study or until withdrawal from participation or death." I am still waiting for the long term lung cancer postmarking trial on cigarette smoking. www.fda.gov/TobaccoProducts/
straight arrow?
1.
Since the first Surgeon General’s report on smoking and health in 1964, there have been more than 20 million premature deaths attributable to smoking and exposure to secondhand smoke. Smoking remains the leading preventable cause of premature death in the United States.
2.
Despite declines in the prevalence of current smoking, the annual burden of smoking-attributable mortality in the United States has remained above 400,000 for more than a decade and currently is estimated to be about 480,000, with millions more living with smoking
United States of America/Population
318.9 million (2014)
Carry on
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Post by rockstarrick on Jul 13, 2016 8:59:27 GMT -5
Can this study be used for updating the label ?? Beginning not later than 18 months after approval, scientists from the Office of Surveillance and Epidemiology and Office of New Drugs in the Center for Drug Evaluation and Research (CDER) jointly review the relevant data, summarize findings and, when necessary, develop a plan to further investigate potential new safety issues for products regulated by CDER. For medical products regulated by the Center for Biologics Evaluation and Research, this safety review and evaluation is conducted by scientists from CBER's Office of Biostatistics and Epidemiology and the relevant product office (Office of Blood Research and Review, Office of Vaccine Research and Review, or Office of Cellular, Tissue and Gene Therapies). FDA compiles the postmarket safety evaluations and periodically posts the summary reports on this website. For additional information about postmarket drug and biologic safety issues, including FDA Safety Communications and web postings of Potential Signals of Serious Risks Identified from the FDA Adverse Event Reporting System (FAERS), please refer to FDA's website on Postmarket Drug Safety Information for Patients and Providers or Safety and Availability (Biologics). www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/ucm204091.htmI guess I'll have to try to find the answer,, it definitely looks like the fda approved label is considered when conducting this evaluation. What information does FDA consider for these postmarket safety evaluations? FDA assesses several data sources including: The product's pre-approval safety profile The product's current FDA-approved label Reports made to the FDA Adverse Event Reporting System (FAERS), previously known as AERS Reports made to the Vaccine Adverse Event Reporting System (VAERS) Manufacturer-submitted periodic safety reports Medical literature Drug utilization databases Data from post-approval clinical trials and other studies, when applicable |
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Post by peppy on Jul 14, 2016 9:54:06 GMT -5
Can this study be used for updating the label ?? Beginning not later than 18 months after approval, scientists from the Office of Surveillance and Epidemiology and Office of New Drugs in the Center for Drug Evaluation and Research (CDER) jointly review the relevant data, summarize findings and, when necessary, develop a plan to further investigate potential new safety issues for products regulated by CDER. For medical products regulated by the Center for Biologics Evaluation and Research, this safety review and evaluation is conducted by scientists from CBER's Office of Biostatistics and Epidemiology and the relevant product office (Office of Blood Research and Review, Office of Vaccine Research and Review, or Office of Cellular, Tissue and Gene Therapies). FDA compiles the postmarket safety evaluations and periodically posts the summary reports on this website. For additional information about postmarket drug and biologic safety issues, including FDA Safety Communications and web postings of Potential Signals of Serious Risks Identified from the FDA Adverse Event Reporting System (FAERS), please refer to FDA's website on Postmarket Drug Safety Information for Patients and Providers or Safety and Availability (Biologics). www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/ucm204091.htmI guess I'll have to try to find the answer,, it definitely looks like the fda approved label is considered when conducting this evaluation. What information does FDA consider for these postmarket safety evaluations? FDA assesses several data sources including: The product's pre-approval safety profile The product's current FDA-approved label Reports made to the FDA Adverse Event Reporting System (FAERS), previously known as AERS Reports made to the Vaccine Adverse Event Reporting System (VAERS) Manufacturer-submitted periodic safety reports Medical literature Drug utilization databases Data from post-approval clinical trials and other studies, when applicablequote; Data from post-approval clinical trials and other studies, when applicable The clamp study was a post approval FDA requirement. I think it is considered phase 4 in the sequence. I started to look for the fda document outlining post approval requirements. The team at MNKD knows whether these results can be used to change the label. Mike did not mention any label change work being initiated with the FDA at the Cantor Fitzgerald's 2nd Annual Healthcare Conference
the obvious differences between afrezza and other fast acting, End of effect
• On a dose basis, the effect of Afrezza ends 2 h before Lispro Onset of activity for TI occurred ca. 25-35 minutes earlier than for
Lispro. TI duration of action is about 2 hours shorter than an equivalent
dose of Lispro. Dose-response was almost linear up to 48U TI and 30 U. www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf the time differences are huge. The FDA does not have a category for this type of insulin, in that afrezza is faster than fast acting. IF the FDA was to want accurate labeling, a case could be made for a label change I would think. Cheaply.
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Post by peppy on Jul 14, 2016 10:24:03 GMT -5
I can see the news paper articles now.
FDA creates ultra fast insulin category to meet the scientific data of technosphere insulin Afrezza.
Made up clip:
"Today the FDA approved a new category of insulin, ultra fast acting.
ultra fast acting insulin starts acting with in 15 minutes of dosing and the duration of action is 2 hours shorter than fast acting insulins."
Mannkind corporation, the company that makes Afrezza technosphere insulin will be changing the Afrezza label to ultra fast acting insulin."
Ask your doctor if afrezza ultra fast acting technosphere insulin is for you. In my dreams.
Pep
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Post by agedhippie on Jul 14, 2016 10:24:49 GMT -5
I suspect you cannot change the label with the study. The performance data already existed from the Phase III trials and is accounted for in the label. What was missing was the linearity data.
The intent of the study is to see at what size the Afrezza dose became non-linear. Because SC insulin forms a pool under the tissue the speed at which it can get into the blood vessels is limited by the surface area of the pool. This is the absorption rate issue that I go on about. If you need more than 50u of insulin you really want to split it into multiple shots.
What the poster did was use the study as a means of putting the response curve out there front and center at the ADA. A lot of the attendees are going to see that and take it onboard regardless of the label or original purpose of the study.
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Post by agedhippie on Jul 14, 2016 10:30:52 GMT -5
Just generally there are a few things that people overlook when they talk about Afrezza because they don't use SC insulin. The focus is always on needles and injecting in public and those benefits are a long way down most insulin users lists. I don't think I have ever seen anyone talk about the preservatives used insulin (meta-cresols) which is why some people get injection site reactions, or nickel allergies which are difficult as most needles are stainless steel. Even absorption is far more important than fast clearance, if I have predictable absorption I can safely stack insulin.
Minor rant over!
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Post by sweedee79 on Jul 14, 2016 13:57:07 GMT -5
I think I remember Matt saying they would be using the results of the clamp study to seek label changes... I believe this was at the annual shareholder meeting...
check at the 53 minute mark of this annual shareholder meeting video.....
vimeo.com/167332167
they say they will be able to use the clamp study and will be seeking label change this year.. FDA also required a certain long and expensive safety study which I have heard no mention of being done yet.. so I don't see the black box warning being changed for a while..
I have a feeling all of the label changes we want will be a process. and require more than one visit to the FDA .. but at least they are making an effort and using what they have which is good.. |
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Post by petech on Jul 14, 2016 14:16:02 GMT -5
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Post by compound26 on Jul 14, 2016 14:21:56 GMT -5
Mike C. also commented that the clamp study and the ADA abstracts (papers) related to the PK/PD profile of Afrezza will be critical differentiators compared to other insulins and foundation for a FDA filing for label change in his presentation on this past Tuesday (July 12). See summary of the presentation. mnkd.proboards.com/post/73176See the video of the presentation at wsw.com/webcast/cantor4/mnkd/index.aspx. The comment was made at 11'30" of the presentation. |
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Post by lakon on Jul 14, 2016 14:22:41 GMT -5
Just generally there are a few things that people overlook when they talk about Afrezza because they don't use SC insulin. The focus is always on needles and injecting in public and those benefits are a long way down most insulin users lists. I don't think I have ever seen anyone talk about the preservatives used insulin ( meta-cresols) which is why some people get injection site reactions, or nickel allergies which are difficult as most needles are stainless steel. Even absorption is far more important than fast clearance, if I have predictable absorption I can safely stack insulin. Minor rant over! MattB mentions preservatives here: afrezzadownunder.com/afrezza-insulin/ and www3.epa.gov/ttn/atw/hlthef/cresols.html. "Mixed cresols are also strong dermal irritants. No information is available on the chronic (long-term) effects of mixed cresols in humans, while animal studies have reported effects on the blood, liver, kidney, and central nervous system (CNS), and reduced body weight, from oral and inhalation exposure to mixed cresols. Several animal studies suggest that o-cresol, m-cresol, and p-cresol may act as tumor promotors. EPA has classified o-cresol, m-cresol, and p-cresol as Group C, possible human carcinogens." Also, here afrezzadownunder.com/tresiba/. "Tresiba gives less than half the daily dose of m-cresol compared to Lantus or Levemir, along halving the phenol dose of Levemir. In addition, Tresiba 200 is available which further halves both phenol and m-cresol." It's good the FDA is making sure Afrezza gets checked out thoroughly for long-term safety, perhaps two or three times even, just to be really really sure that the genius billionaire playboy philanthropist got it right. What's the FDA's take on cresols and analogs? Nickel allergies -- sure they have those too. "REVIEW ON TOXICITY OF STAINLESS STEEL" www.ttl.fi/en/publications/Electronic_publications/Documents/Stainless_steel.pdfConsider this: Porcine (pork) insulin has one different amino acid. Bovine (beef) insulin has three different amino acids. In Humalog (Insulin lispro), the penultimate lysine and proline residues on the C-terminal end of the B-chain are reversed. In NovoLog/NovoRapid (Insulin aspart), the amino acid, B28, which is normally proline, is substituted with an aspartic acid residue. In Apidra (Insulin glulisine), the amino acid asparagine at position B3 is replaced by lysine and the lysine in position B29 is replaced by glutamic acid. Do you see it yet? The elephant is standing right next to you. I'm not sure that even absorption is far more important than fast clearance. I'd agree that they are both important. It's good that Afrezza has both, but I'm sure you could just evenly distribute your 1 shot into many shots across your body to get the same effect -- kind of like the picture of the girl with all the shots at once or possibly creating Mrs. Captain America...  Also, you can unsafely stack insulin. That's the rub. To be clear, I did LIKE your rant agedhippie. |
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Post by Deleted on Jul 14, 2016 14:36:40 GMT -5
Mike C. also said that the clamp study and the ADA abstracts will be foundations for a label change in his presentation on this past Tuesday (July 13). See summary of the presentation. mnkd.proboards.com/post/73176The day of those results will be a vicious move but given what MNKD has gone through I can't see the FDA approving this on a 30 person trial. I hope to be proven wrong. |
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Post by matt on Jul 14, 2016 15:28:34 GMT -5
The day of those results will be a vicious move but given what MNKD has gone through I can't see the FDA approving this on a 30 person trial. I hope to be proven wrong.
FDA is fairly practical on these matters, and whether a 30 patient trial is enough depends on the particular label change. The pharmacodynamics data that FDA approved in the label was developed from just 12 patients so if there is a cohort of 30 that gives a different (but not totally different) answer then it might be enough.
The tricky bit is that there is one set of claims in the label that were agreed to based on data that was claimed to be reliable. If there is new, and different, data then it is fair for FDA to ask some tough questions like:
"Do we believe the data you showed us when we approved the drug, this new data, or should we make you run a trial of 100 patients to break the tie before deciding?"
"If you say the new data is reliable but the old data was not, does that mean everything we based the approval on should be considered unreliable?"
Answers to those questions are not easy. Changes in labels always open a can of worms and the answer might not be what shareholder want. Still, given where the company is the risk is probably worth it if there is chance to improve sales.
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