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Post by agedhippie on May 2, 2018 18:43:07 GMT -5
Reading the summary review was interesting. I had thought that the FEV-1 requirement was to mitigation the risk to patients with undiagnosed underlying lung disease that would render them at risk from bronchial spasm. However that is not the case although it was identified as a serious risk and doctors are required to ensure that patients were evaluated to detect undiagnosed underlying lung disease exactly how they were to do that was not prescribed ("No consensus on best approach was reached.")
The FEV-1 was mandated to establish a baseline for lung function, and monitor for the risk of significant pulmonary function decline. If it can be proved that there is no lung function decline that requirement could be removed - the 5 year lung safety trials could provide that data although it is not that trial's purpose.
What happened in the end was that the REMS notification told doctors that they need to evaluate all patients for lung disease before starting AFREZZA. To do this they must perform; "a detailed medical history, physical examination, and spirometry (FEV1)". That is prescriptive, and the REMS ensured that all doctors are (or should be) aware of what needs to be done. If a doctor doesn't follow those requirements and the patient has a bronchial spasm things would not look good for the doctor (to put it mildly).
At this point someone is going to say that the REMS is complete so this no longer applies. No, the REMS is complete because all doctors have been told that they must do this and ignorance of the requirement cannot now be used as an excuse.
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Post by sayhey24 on May 2, 2018 19:51:49 GMT -5
Mango - Aged is correct the FEV1 testing was included in the REMS because of the concern that diabetics loose lung function as they age faster than the general public. With the immediate decline for new users the concern on the part of the FDA was it could be a real problem. www.diabetes.org/newsroom/press-releases/2008/reduced-lung-capacity.htmlWhats being seen after 3 years of use is that in general afrezza users are not loosing lung function and some are reporting improved lung function. What we do know is, if the black box and spirometry were in fact part of the REMS then it will take another sNDA to change the label. At this point we do know for a fact is the REMS Communication Plan is done and therefore the REMS is complete too. Why? Because if you remove the communication plan you are no longer required to tell anyone about associated REMS requirements. Therefore in the 4/24 FDA letter they concluded the REMS was gone too. It seems like reverse logic and odd to me. I would think first you remove the REMS and then the REMS communication plan is not needed. How the FDA decided to make this decision "with out data, reviews and panel approval" is still a mystery. How they did this in 5 days is a bigger mystery. An sNDA completed and approved in 5 days, WOW! The new administration must really be shaking things up or another sNDA marked "confidential" was approved prior and has not yet been disclosed. The simple answer could be MAGA but I doubt it. |
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Post by digger on May 2, 2018 20:49:44 GMT -5
Your first sentence is blatantly untrue! Be careful not to make those kind of erroneous statements if you don't know trial history. This is not Yahoo or StockTwits. Incidentally, the trial data does NOT support it. The ADCOM physicians all agreed that the incidence were so few as to render them not statistically significant. Caution was suggested with patients with COPD, but not a mandated lung test on all patients before prescribing. That was entirely a renegade final action by the FDA. When they couldn't stop it's approval, they added a barrier that would make Afrezza much more difficult to prescribe, IMO. This was at the time when the FDA Commissioner's husband, a hedge fund manager, had MNKD holdings. Those fund records have also been posted on ProBoard. I don't even know what the trial data said in either exubera's or afrezza's case as regards bronchospasm. I just point out that evidently whatever the FDA saw in exubera's data was not enough to earn a black box, while whatever they saw in afrezza's data was enough to earn a box. That seems like a reasonable assessment under the circumstances. I'm not arguing about the data, but only about the prospects of removing the box. Given what the FDA found, they obviously concluded that it would put patients at risk of serious consequences if lung disease were not satisfactorily ruled out. I can't think of anything Mannkind can do to change that. Note that there is no gun to the head of the doctor. If he wants to ignore the black box, he has the authority. His only risk would be if something bad happened and he faced a malpractice suit for ignoring the warning. |
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Post by digger on May 2, 2018 21:00:29 GMT -5
By the way, all of the lung warning stuff came from Mannkind itself:
"Afrezza has not yet been approved and product labeling has not been finalized. However, Mannkind has proposed in the Afrezza labeling that Afrezza be contraindicated in patients with a current diagnosis or history of asthma, chronic obstructive pulmonary disease (COPD) or other chronic lung disease. The sponsor also has proposed labeling under Warnings and Precautions that Afrezza not be recommended for current smokers and those who have smoked in the last 6 months and that prior to initiating therapy with Afrezza, all patients should be clinically evaluated with a detailed medical history, physical examination and spirometry (FEV1) to identify any potential underlying disease."
So I don't think you can blame the FDA for that. I don't at what point or why the black box became important to the FDA.
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Post by dreamboatcruise on May 3, 2018 4:59:13 GMT -5
Even if the black box is retained the mandatory requirement for a FEV1 test of every patient can certainly be removed. For example, Afrezza is not recommended for women who are pregnant. Why not throw in a mandatory pregnancy test into the black box? The FEV1 is an unnecessary "what-if" that a narrow-minded (or corrupt) FDA attached to the black box. Even Exubera didn't have it, and that inhaled insulin powder was far more dangerous than inert Technosphere particles. What made it more dangerous... I just thought that was SNY killing it. Though it was an awful delivery device without the pk/pd benefit of Afrezza. |
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Post by mnholdem on May 3, 2018 7:41:57 GMT -5
Shifting gears. There is also an economic impact of REMS. The following is an excerpt from a 2011 study How REMS Affect Pharmaceutical Distribution Processes and Partners:
Stakeholder perspectives
Sample groups of manufacturers, distributors and healthcare providers provided comments on concerns or priorities in administering REMS programs. All study participants expressed reservations about delays that ultimately may hinder patient access to drugs.
REMS Costs to Supply Chain The study’s economic analysis indicates REMS requirements are costly to the supply chain and underscore the need for additional research into REMS program costs, including those that are hidden, unforeseen and not reimbursable through current business practices and government benefit programs.
REMS Costs to Manufacturer For manufacturers, costs are divided between setup and monthly maintenance. Each line item ranges from a low of $5K-250K, to a high of $100K-500K. Development times range from 20 to 120 days, depending on the task. For distributors, line items range from “minimal” to $5K-$1M (indicative of the wide range of data reporting that can be required).
REMS Costs to Healthcare Providers Healthcare provider economics are evaluated on the basis of time estimates to complete various tasks; for example, physicians’ patient counseling is 10-15 minutes (per patient), while physician certification can require an hour.
Fuller details are available in the report.
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Studies have demonstrated that having a REMS requirement attached to a drug is costly and does cause "delays that ultimately may hinder patient access to drugs". |
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Post by liane on May 3, 2018 7:43:16 GMT -5
Even if the black box is retained the mandatory requirement for a FEV1 test of every patient can certainly be removed. For example, Afrezza is not recommended for women who are pregnant. Why not throw in a mandatory pregnancy test into the black box? The FEV1 is an unnecessary "what-if" that a narrow-minded (or corrupt) FDA attached to the black box. Even Exubera didn't have it, and that inhaled insulin powder was far more dangerous than inert Technosphere particles. What made it more dangerous... I just thought that was SNY killing it. Though it was an awful delivery device without the pk/pd benefit of Afrezza. I don't have time to look it up now, but I seem to recall that the Exubera excipients (mannitol, citrate, glycine, and sodium hydroxide) took a little longer to clear out of the lung tissue - perhaps an hour. This vs Technosphere which is minutes. So there is a longer exposure to these materials, of unknown significance. |
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Post by mnholdem on May 3, 2018 7:46:35 GMT -5
Additional studies have demonstrated how REMS increases the cost of sales as well, as this excerpt explains:
REMS in Pharmaceutical Sales Training
When a REMS has been imposed by the FDA, it obviously affects pharmaceutical sales training. Pharmaceutical reps have to understand how any drug they market that is subject to REMS is affected, and what specific elements are required under any applicable REMS. When a REMS requires specific educational materials for prescribers and patients, pharmaceutical reps have to be adequately trained so they know which materials are required, what's in the materials, and how to effectively present them to prescribers and patients. In other words, REMS adds another layer of knowledge required of the sales rep when a REMS applies to the products he or she markets.
Why REMS Compliance Is Critical
When a REMS has been imposed, noncompliance can bring serious consequences, so everyone involved, from drug production through marketing via pharmaceutical sales reps has to understand the regulations. Not complying with REMS can bring about warning letters, fines, and even criminal charges. Corporate and personal liabilities from REMS noncompliance include:
• Civil monetary penalties of up to $250,000 per violation
• A declaration of drug misbranding
• Prohibition of introducing a drug into interstate commerce
• Criminal sanctions (misdemeanor or felony)
• Warning letters
• Ability of the FDA to withhold actions on other pending applications
• Exclusion of companies from participating in FDA-regulated activities
• Exclusion from federal healthcare programs
And of course, reputational damage and public relations problems can result as well.
Pharmaceutical sales trainers have to thoroughly understand the FDA requirements for developing REMS programs that are compliant so that sales reps can do their jobs without running afoul of REMS requirements. |
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Post by prcgorman2 on May 3, 2018 10:06:25 GMT -5
“Impossible”? That means they absolutely cannot have it removed. Pretty strong wording there digger. I’m curious to know what is your background, education and experience pertaining to FDA regulations? See my previous comment. To me, this is a simple exercise in logic. The trials showed people with lung disease were at risk for developing bronchospasms that were severe enough to merit the black box. In other words, the trials have proven that this group of patients is at risk. What choice is there but to assess afrezza potential patients to determine whether they too might have lung disease sufficient to put them at risk for severe bronchospams? I'll stipulate to simple logic. I think mnholdem's comments are still persuasive (especially about Exhubera being more dangerous - at least from a perspective of hypoglycemia if not also lung function). I also suspect changing the black box warning (hopefully for the better from an Afrezza marketing perspective) is an independent variable from the elimination of the REMS requirement. That said, getting other's information or opinions on this point is one of the main reasons I asked the question that started the thread. |
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