As an investor in MNKD (or any company for that matter), it's always prudent to know the good and bad info out there that could impact your decision making process or investment. It can also pertain to being a patient of a new drug in this case as well. I probably haven't been an investor as long as many on this board but I find it beneficial to evaluate an investment from time to time. The reason I bring this up is lately I have been seeing and hearing issues on lung toxicity or "it will cause cancer" again on Stock Twits, here, there and even from very close doctors I know that have been in practice for over 30 years (pulmonary and one with experience in diabetes). Their concern was over a long period of time.
We all know it's used as a scare tactic but it's a valid concern, especially from a patient's point of view and my guess is that it's going to be regurgitated many times more in the future.
Thanks to this board and wealth of knowledge from it's members, it's a great place to find valuable and insightful information which makes the process of researching much easier. However, it has been difficult to find info to backup the answer of NO it doesn't and/or here's why it doesn't or based on this it's a very slim chance. When I post info or statements to places I like to have data to post to backup my statement, unlike many on other boards where people like to call the drug a "scam" or "it causes lung problems/cancer" without any data to backup their claims.
Maybe there should be a sticky post called "Does Afrezza cause cancer?" and put all the info below in it, so it's easy to find and can be referenced by people when the subject comes up? I found the following thread which contained some quotes from Alfred Mann as well as references to some studies done but no links to those studies to see the actual info. After doing some digging I have found the info that can be used as reference if people want to actually see the outcome of the studies (I've added them into the info I found from the thread). Some do have to be purchased to see the full info though.
I also think Dave's link from tudiabetes.org should be included as well since he's investigating the question and providing easy to understand answers to very complex information. If anyone else has links to other studies (godd or bad) those should be added as well.
It's also brought up that it's (insulin) a human growth factor and that could cause lung issues when using over a decade or longer. My question is how does this compare to inhaling steroids or corticosteroids? Advair, Symbicort, Singular, etc? I don't currenlty know the answer to this or if it's even a valid comparison.
Also after reading the info below you realize that this drug is over 10 years old and has probably gone through more testing than half the drugs on the market. There are obviously a lot of factors that can be involved that could contribute to possible cancer, such as ex-smoker, environment you live in, etc, etc but so far from the studies they hasn't shown any significant possibility.
Hope this post helps in some way.
Does Afrezza cause cancer?
You decide...
Below is a compilation of quotes, studies and articles that go back to 2005 that can help you make your decision.
Original thread credit:
mnkd.proboards.com/thread/327/question-re-lung-toxicity#ixzz3UP9XSzMT"It seems to me that the concern about lung cancer should have ended by now since there is no factual basis for such concern. Even for Exubera, there was no conclusion as to causality or acceleration and AFRESA is so very, very different. In relation with AFRESA, it is certainly less risky than for some other chronically entailed drugs and even less so than breathing in a large city. An advisory committee has dismissed any risk of lung cancer from AFRESA. While we are seriously concerned about this risk, all of the data gives us confidence that any concern about lung cancer with AFRESA is without foundation and is bogus. Nevertheless, we must address some perceptions that have been created."
-Alfred Mann
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MannKind has also undertaken a more comprehensive examination of the toxicology profile of Technosphere(R) Insulin than has been reported for any other inhaled insulin. Last year, MannKind completed a two-year carcinogenicity study in rats in which Technosphere(R) Insulin, and large doses of Technosphere(R) particles alone, were well tolerated after daily inhalations for 104 consecutive weeks. There were no indications in these studies that either Technosphere(R) Insulin or Technosphere(R) particles alone had any carcinogenic potential or caused any cellular proliferation in the lungs. MannKind also recently completed a six-month carcinogenicity study in transgenic mice, finding no macroscopic indications of carcinogenicity in animals given daily subcutaneous injections of Technosphere(R) Insulin or Technosphere(R) particles for 26 consecutive weeks. In addition, MannKind plans to submit data from over 100 preclinical studies supporting the safety of our product, the vast majority of which have already been completed.
LONG-TERM PULMONARY SAFETY ASSESSMENT OF AFREZZA™ IN RATS AND DOGS.
www.toxicology.org/AI/Pub/Tox/2011Tox.pdf (Page 179)
S. Greene1, K. Nikula2, J. Reynolds3, D. Poulin4, K. McInally5, D. Townson1
and P. Richardson1. 1MannKind Corp, Valencia, CA, 2Seventh Wave Laboratories,
Chesterfield, MO, 3J.A. Reynolds & Associates, Madison, CT, 4Charles River
Laboratories, Montreal, QC, Canada and 5ITR Laboratories, Montreal, QC, Canada.
The inhalable insulin Afrezza™ was evaluated in nonclinical safety studies as a
New Molecular Entity (NME) for diabetes treatment. Chronic inhalation and carcinogenicity
studies were conducted in Sprague Dawley rats and a chronic inhalation
study was conducted in Beagle dogs. Daily doses of either the novel excipient
Technosphere® (fumaryl diketopiperazine) particles or various doses of Afrezza™
(insulin adsorbed to Technosphere particles) were administered by the nose-only
(rats) or oronasal (dogs) routes. Tissues were evaluated by histopathology and respiratory
cell proliferation was assessed by immunostaining of proliferating cell nuclear
antigen (PCNA). There were no test article-related changes in the laryngopharynx,
larynx, trachea, bronchi or lung of rats. Test article and Technsophere
particle findings in the nasal cavity of rats were limited to the presence of
eosinophilic globules in the olfactory and respiratory epithelium that were considered
nonspecific responses to chronic, high level administration of particulate materials.
After 39-wks in dogs, there was a low incidence of minimal to mild alveolar
and/or bronchial interstitial neutrophil infiltrate in the lungs at the high Afrezza™
dose. This cellular infiltrate regressed completely during the 8-wk recovery period.
Based on evaluation of H&E stained tissues, there was no evidence of amyloid deposition
in any portion of the respiratory tract in either species. Inhalation of
Afrezza™ up to 104 wks in rats and 39-wks in dogs did not increase PCNA labeling
in alveoli, large bronchiolar or terminal bronchiolar tissues. Based on no test article-related
adverse findings in the lungs or increases in cell proliferation in rats or
dogs, the no adverse effect level was established in both species as the highest studied
doses. Chronic inhalation of Afrezza™ was well tolerated and supports the safe
use of this NME in humans over extended periods.
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"We also did high-definition CT scans on the 600 patients in our study. That’s the best you can do with people. We saw no change in their lungs, and some of them have been using the product for up to 5 years now."
-Al Mann
www.healthline.com/diabetesmine/the-truth-about-afresa-inhalable-insulin-a-chat-with-al-mann#3---------------------------------------------
Mannkind has stated categorically that they have not found any more lung cancer in Technosphere Insulin-using patients than that in the general population. In their May 5th conference call, Mannkind said that up till then they have had 4,849 patients in 25 completed and 7 ongoing trials, 2,684 which used Technosphere Insulin and 2,165 which were controls. In patient-years, they have so far had 2,182 patient-years using Technosphere Insulin and 1,708 patient-years using controls. In all that, they have found 1 case of lung cancer, plus 1 case of lung involvement in metastatic colorectal cancer. A metastatic cancer is one in which the tumor has spread from its primary site in the body to another site. This patient was found to have colorectal cancer which then spread to the lung, and clearly does not reflect at all on the lung cancer risk with Technosphere Insulin. One case (who was a former smoker, by the way) out of 2,182 patient-years comes out to a cancer rate of .046%, lower than that normally found in the general population.
Pulmonary function over 2 years in diabetic patients treated with prandial inhaled Technosphere Insulin or usual antidiabetes treatment: a randomized trial
www.readcube.com/articles/10.1111%2Fj.1463-1326.2011.01500.x?r3_referer=wol&tracking_action=preview_click&show_checkout=1&purchase_referrer=onlinelibrary.wiley.com&purchase_site_license=LICENSE_DENIED_NO_CUSTOMERAims: Development of inhaled insulin has increased the need to understand its pulmonary safety. This study evaluated pulmonary function changes in diabetes patients receiving inhaled Technosphere Insulin (TI) or usual antidiabetes treatment (usual care).
Methods: This randomized, open-label study was conducted at 220 sites (25 July 2005 to 29 August 2008). Pulmonary function tests [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), total lung capacity (TLC) and lung diffusion capacity for carbon monoxide (DLCO)]were prospectively followed over 2 years in patients with type 1 or type 2 diabetes receiving TI (n = 730) or usual care (n = 824), along with a cohort without diabetes not receiving any special therapy (n = 145).
Results: Baseline demographics and pulmonary function were similar between diabetes treatment groups. Lung function declined frombaseline in all groups. TI was non-inferior to usual care for mean change in FEV1from baseline to month 24 [mean (s.e.m.) 0.037 (0.0119) l;95% CI 0.014 to 0.060] using mixed-model repeated-measure with a pre-speci?ed non-inferiority margin of 50 ml/year. After a greater initialdecline at month 3 with TI, rate of change (slope) in FEV1, FVC and DLCO(months 3–24) was not statistically different between treatment groups. TI was well tolerated; no serious safety concerns emerged. The most common respiratory event associated with TI was mild, transient cough, occurring within minutes of inhalation.
Conclusions: Observed changes in lung function with TI were small, occurred early after therapy initiation, remained non-progressive over 2 years and were unlikely to be clinically meaningful.
Keywords: diabetes, inhaled insulin, pulmonary function, Technosphere Insulin, usual antidiabetes treatment
Date submitted 30 June 2011; date of first decision 2 August 2011; date of final acceptance 20 September 2011
Safety of Technosphere Insulin as an Ultra-Rapid-Acting Prandial Insulin
www.ncbi.nlm.nih.gov/pmc/articles/PMC3440146/The safety of TI has been studied extensively, both preclinically and in a clinical program involving more than 5600 subjects. The most common treatment-emergent adverse events were hypoglycemia, cough, and upper respiratory tract infection.17 Cough occurred in approxi-mately 32% of patients administering TI but tended to be mild and transient, occurring within minutes of inhalation.17 Furthermore, cough diminished over time and rarely led to study discontinuation.
A pooled analysis of cardiovascular events from nine clinical studies comprising 4467 patients who administered TI or usual diabetes care showed that the incidence of cardiovascular or cerebrovascular events was similar between the TI and usual diabetes care groups (relative risk, 1.01; 95% CI, 0.84 to 1.20).23
Lung function was examined in a 2-year prospective, multicenter, randomized, open-label study in patients with type 1 or type 2 diabetes administering TI (n = 730) or usual diabetes care (n = 824) and a cohort without diabetes who did not receive any specific therapy (n = 145).24 Lung function declined from baseline in all treatment groups, in line with normal age-related changes and as seen in diabetes in general. Compared with usual diabetes care, TI showed a small reduction in forced expiratory volume in 1 s (FEV1) from baseline to month 24 (-0.037 ± 0.0119 liter; 95% CI, 0.014 to 0.060). After a greater initial decline by month 3 with TI, the rate of change (slope) in FEV1, forced vital capacity, and diffusing capacity of the lung for carbon monoxide over months 3 to 24 was not statistically different between treatment groups. This observed treatment group difference was small, occurred early after therapy initiation, did not progress over 2 years, and resolved after discontinuation of therapy.
Two cases of cancer involving the lung have been reported during clinical trials, both in ex-smokers. The incidence does not exceed what would be expected in a similar, nontreated population.25 A 2-year carcinogenicity study in rats26 and a 6-month study in transgenic mice (data on file, MannKind Corporation) did not indicate a carcinogenic potential.
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Technosphere® Insulin: Defining the Role of Technosphere Particles at the Cellular Level
www.ncbi.nlm.nih.gov/pmc/articles/PMC2769873/pdf/dst-03-0545.pdf---------------------------------------------
Insulin Lung Deposition and Clearance Following Technosphere® Insulin Inhalation Powder Administration
link.springer.com/article/10.1007/s11095-011-0443-4Purpose
To determine distribution and deposition of Technosphere® Insulin (TI) inhalation powder and the rate of clearance of fumaryl diketopiperazine (FDKP; major component of Technosphere particles) and insulin from the lungs.
Methods
Deposition and distribution of 99mpertechnetate adsorbed onto TI immediately after administration using the MedTone® inhaler was quantified by gamma-scintigraphy. Clearance from the lungs was studied in a second experiment by serial bronchoalveolar lavage (BAL) after administration of TI inhalation powder and assay of the recovered fluid for FDKP and insulin.
Results
Following inhalation, ~60% of radioactivity (adsorbed on TI) emitted from the inhaler was delivered to the lungs; the remainder of the emitted dose was swallowed. Clearance from the lung epithelial lining fluid (ELF) of FDKP and insulin have a half-life of ~1 hour.
Conclusion
TI inhalation powder administered via the MedTone inhaler was uniformly distributed throughout the lungs; ~40% of the initial cartridge load reached the lungs. Insulin and FDKP are quickly cleared from the lungs, mainly by absorption into the systemic circulation. The terminal clearance half-life from the lung ELF, estimated from sequential BAL fluid measurements for both components, was ~1 hour. Since there is an overnight washout period, the potential for accumulation on chronic administration is minimal.
---------------------------------------------
davetud from tudiabetes.org
www.tudiabetes.org/forum/topics/wary-of-interested-in-using-afrezza-you-should-read-thisLike many, I was concerned about just what exactly was happening in my lungs when Afrezza is put into it. I'm especially attuned to this question having followed some injectible "ultrafast" insulins being developed, and the biochemical techniques used to speed absorption.
The way that stuff works scares me when lung tissue is in play.
Fantastic news about Afrezza: The "magic" is nothing more exotic than a purely passive, non-chemical approach. Further the carrier, Technosphere (Mannind's invention) is composed of only N, O, and H in a very simple molecule, fumaryl diketopiperazine (FDKP -- name sounds scary, but then so is dihydrogen oxide if you don't know that that's H2O). The key is the mechanical folding of the molecule, which makes it fairly porous. Insulin sticks to it, but Technospheres generally don't like to stick to each other, so they don't clump and are easily dispersed into an atomized cloud.
