by DrKSSMDPhD | June 20, 2016 5:44 am
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RE: Califf and emerging direction of the FDA
I am not pre-judging the future success or failure of Califf’s FDA administration, but have some comments that may be relevant.
My working life was mostly in the retail business, obviously a completely different and much less technical field than medicine or law or government. But from that experience I can say that the skills needed to run a large organization effectively are quite unique, and often quite different from the skills needed by individuals who are lower in the ranks, or who are from related industries.
The skills be completely lacking in what would appear otherwise to be a perfectly qualified individual,
aside from any philosophical or strategic inclinations.
For example, in a large retail organization, successfully performing individuals at lower levels often simply cannot perform effectively at higher levels. Not all assistant buyers make successful buyers; not all successful buyers can run divisions; not all vice presidents will be effective presidents. And there is often no way to be sure which ones will do well, and which ones will not.
I would think being in charge of an organization like the FDA has requirements an skills for which it may be nearly impossible to prepare. Being qualified medically or scientifically may be a necessary requirement, but that is not the same as providing effective leadership and direction to a large and complicated enterprise.
I am certainly not qualified to pass judgement on the job performance of Califf or anyone else in a similar position of responsibility; I only point out that there are no guarantees of how he will
perform in his responsibilities. Time will tell.
$ZFGN…tougher FDA…if the FDA proves to be more difficult than in the past, it will deflate the price of risk premiums that the market is willing to pay for these clinical companies. We have already witnessed
the impact of less risk appetite in the recent bear correction, and extreme punishment on pricing for mistakes. These have been from rather frothy price levels, and most of us have the scars and black-and-blue marks as souvenirs.
I would surmise that the prices before success will be at generally lower levels and multiples than we have seen. So if our picks are good, we will get them relatively cheaper than before.
Honor Roll post.
Basically I think Califf is telling his chieftains, If in doubt, strike it out. If it takes you more than 30 minutes to decide, there must be something hanging in your craw about it, and you should decline/refuse/issue a CRL. That is Califf thinking. Under Hamburg, the process was entirely more democratic and reliant upon the art of suasion as wielded by presenters.
ZKSS, thank you for further clarifying the Zika, non-problem…
$RGLS is mentioned in the report above but I am guilty of over-hyping the issue; I apologize. With your permission, I shall update the AOZ thread: AOZ thread: http://www.stockgumshoe.com/2016/04/microblog-aoz/
#Alzheimer’s_disease , #Obesity , #Zika – The #Numbers , #$s , #Mystery , #KASH ; #Past #present & #future
… with #Zika, $ZFGN – obesity and $AXSM – Alzheimer’s data from threads and twitter. I shall be glad when they get the replicator and transporter completed as to send you the hot-cabbage dish prepared today. My dad ate it everyday for lunch for over 15 years. – Jammin’
$KSS…Doc, great to see you back, and thanks for $RLYP.
Without you I surely would never have heard of it, let alone had the courage to buy stock in it.
SoGiAm, Ben…I just read the interview on Speaking that you referred to and was very impressed. Is this you? Do you have the blog MedicalFuturist? How is your Mom doing? I am still praying every morning for Elsie, and Sharon’s Mom and brother Bobby. A good weekend to all. Most sincerely, Karen
Karen, this is Berci Meskó, MD, PhD
@Berci https://twitter.com/Berci
The Medical Futurist, science fiction fanatic, sharing news, visions and announcements about the exciting future of medicine & healthcare.
Budapest, Hungary
medicalfuturist.com
Joined March 2007
Me: Ben Lawrence; mom is well thank you for asking and your prayers. Hope all is well with you and your family.
TRIL (I own some) anyone figure out article about Anti cancer drug repurposed to prevent muscle wasting? What is the drug? where can you find info on it?
Thanks!
Wild Bill
Researchers Discover Gene that Controls Regeneration of Injured Muscle by Adult Stem CellsFont size: A | A | A
12:00 PM ET 7/21/16 | PR Newswire
A key gene enables the repair of injured muscle throughout life. This is the finding of a study in mice led by researchers at NYU Langone Medical Center and the University of Colorado at Boulder, and published online July 21 in Cell Reports.
http://photos.prnewswire.com/prnvar/20150715/237434LOGO
The study results further suggest that this “overlooked” gene may play an important role in sarcopenia, the loss of muscle tissues with age.
Specifically, the research team found that levels of a single protein known as AUF1 determine whether pools of stem cells retain the ability to regenerate muscle after injury and as mice age. Changes in the action of AUF1 have also been linked by past studies to human muscle diseases.
More than 30 genetic diseases, collectively known as myopathies, feature defects in this regeneration process and cause muscles to weaken or waste away. Clinical presentation and age of diagnosis vary; Duchenne muscular dystrophy develops in infants, limb girdle muscular dystrophy weakens the torso and limb muscles beginning in young adulthood, and sarcopenia occurs in older patients.
“This work places the origin of certain muscle diseases squarely within muscle stem cells, and shows that AUF1 is a vital controller of adult muscle stem cell fate,” says Robert Schneider, PhD, the Albert B. Sabin Professor of Microbiology and Molecular Pathogenesis, and associate dean for the Office of Therapeutics Alliances at NYU Langone.
“The stem cell supply is remarkably depleted when the AUF1 signal is defective, leaving muscles to deteriorate a little more each time repair fails after an injury,” says Schneider.
Tagged for Destruction
The study results revolve around one part of gene expression, in which the instructions encoded in DNA chains for the building of proteins are carried by intermediates known as messenger RNAs (mRNAs). Proteins comprise the body’s structures, enzymes and signals. The expression of certain genes that need to be turned on and off quickly is controlled in part by the targeted destruction of their mRNA intermediates, a job assigned to proteins like AUF1.
The investigators found that among the functions controlled by mRNA stability is the fate of stem cells, which descend from the human embryo, and then multiply and specialize in the womb until they become our bones, skin, muscles, and other tissue types. Some tissues maintain specialized pools of stem cells into adulthood, ready to mature into replacement cells and regenerate damaged tissues as needed.
Following skeletal muscle injury, muscle stem cells receive a signal to multiply and repair damaged tissue, a process that the researchers found is controlled by AUF1. Among the mRNA targets of AUF1 in muscle stem cells, they discovered one that encodes a “master regulator” of adult muscle regeneration, a protein known as MMP9. This enzyme breaks down other proteins, ultimately controlling their expression levels.
The current study found that mice engineered to lack the AUF1 gene showed increased MMP9 activity and reduced stem-cell-driven repair. This “self-sabotages” the stem cell pools that normally repair muscle and destroys the niche in which their muscle stem cells reside as they await activation. Together, this results in a dramatic and continuous breakdown of skeletal muscle.
The investigators showed that they could restore normal muscle stem cell function and related muscle regeneration in mice lacking AUF1 by repurposing a drug developed for cancer treatment that blocks MMP9 activity.
“This provides a potential path to clinical treatments that accelerate muscle regeneration following traumatic injury, or in patients with certain types of adult onset muscular dystrophy,” says Schneider. “We may be able to treat a variety of degenerative diseases by enhancing resident tissue stem cells through targeting MMP9 and its pathways, even those with normal AUF1.”
“It was once thought that AUF1 did no more than tag mRNAs that were not needed so they could be disposed of, a utilitarian protein of little interest,” says first author Devon Chenette, a graduate student who pioneered the work in Schneider’s lab. “To the contrary, our results suggest that AUF1 has evolved to be a key regulator of stem cell fate and the related regenerative ability of adult tissues.”
Along with Schneider and Chenette, Lauren Larkin in the Department of Microbiology at New York University School of Medicine was a study author, along with Jinhua Wang in the Center for Health Informatics and Bioinformatics. Also making key contributions were Adam Cadwallader, Tiffany Antwine, and co-corresponding author Bradley Olwin in the Department of Molecular, Cellular and Developmental Biology at the University of Colorado at Boulder. The work was supported by NIH grants GM085693, R24OD018339, T32 13-A0-S1-090476, and AR049446, as well as by a grant from the Ellison Medical Foundation.
CONTACT: Gregory Williams, 1-212-4043533, gregory.williams@nyumc.org
Logo – http://photos.prnewswire.com/prnh/20150715/237434LOGO
To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/researchers-discover-gene-that-controls-regeneration-of-injured-muscle-by-adult-stem-cells-300301751.html
SOURCE NYU Langone Medical Center
Question of the Day:
Which one of the following characterizes phase I cancer drug testing?
a. It may involve patients with different kinds of cancer.
b. It is limited to patients who have highly effective treatment alternatives.
c. It uses a single dose level to ascertain response rates.
d. It always involves completely predictable toxicities.
C no Google just me..
#Ditto Dan62 ‘cept answer = A 🙂
$ITEK Expands IP Portfolio with Patent on combo with latanoprost, a most prescribed prostaglandin analog #glaucoma https://twitter.com/Lin_ling_88/status/756450608715034625 – Jammin’
E = If you or you love ones suspect Cancer – Get tested NOW!
I concur with C, but A may be read two ways and one of those ways would also seem to be correct — Curt
Phase 1 usually involves dose escalation, so not C; Toxicity relates to safety in humans which is main purpose of a phase 1, so not D; Doubt that B is correct- if a patient already is responding well to another treatment why subject them to a drug with unknowns? My final answer is A.
Well, it’s not C because Cellceutix had many dose levels for Kevetrin, and isn’t that the point of phase 1 anyway? It’s gotta be A. If it were B, that would mean you couldn’t trial for a cancer that had no effective treatment. And D, if you know the toxicities, then why do you need a phase 1 trial?
A -broad sweep to what might be successful
I say it’s A. Phase I is to test safety, and usually you start low and raise dosing until test subjects won’t have it. Since efficiency is not a primary endpoint it’s no problem to include different cancers in the trial.
Best Regards
Noci, long Gummy
A For the reasons just stated by noci. A test of safety/toxicity only.
A read the others carefully
#RTQ Read The Question – #ONCE -Lesson from Insurance teacher, mentor, professional Mr. Stegal. on multiple choice if you do not have a clue the best choice is C. – Jammin’
If toxicity was completely predictable no test would be needed.
Eliminates D
Toxicity could be run on people with no disease.
Eliminates B
Tests are started at low dose and escalated through multiple doses.
Eliminates C
only A remains. What am I missing?
The high-quality reasoning most of you are showing has me practically doing handstands for joy. Most are on the right track. There’s no trick in this question….just bread and butter biotech.
Daily Quiz answer is A. Phase I focus on safety. No need to target a population diagnosed with a specific disease. In fact, the test group could consist of subjects with no diagnosed disease. While companies that design a Phase 1 trial limited to subjects with a specific disease may be rewarded with data that gives early clues re efficacy (positive or negative), there are many variables (e.g., dose; form of administration; duration) that may affect the utility of such data. Bottom line: Key focus in Phase I is safety (toxicity).
Answer, a. Phase 1 is to test for toxicity, to weed out drugs that have serious side effects before spending more money on proving its efficacy. They will probably start with smaller doses, and then increase them, and can use anyone, regardless as to the presence of a specific cancer, although I would think it likely they wouldn’t mind trying it out on people who have the cancer they are targeting just in case it can provide them a sneak peek at efficacy.
Not (C): Dose escalation is normally performed to find the right dose with the least side effects.
Not (D): Finding toxicity (based on dose) is a primary endpoint.
Not (B): There may not be effective alternatives.
(A): Although I would hope priority is given to those with the targeted disease/illness (especially if there are no alternatives), good scientific practice (GSP:) would incorporate people with varying degrees of health.
I’m going A, phase 1 being where dose escalation occurs.
Which rules out C and D.
Not B, Not C, Not D
Ergo A
Chinese scientists get go-ahead for first human CRISPR trial, starts next month http://go.nature.com/2acQ976
#WhenTheFree http://www.stockgumshoe.com/2016/07/microblog-w-t-f/comment-page-1/#comment-4880580
Watching $SCYX closely today. If it breaks the 2.27/30 area could test it 50MA w/catalyst coming. I’m long from 1.98 @crtaylor81 LONG ZKSS, Gummune #SCYX https://pbs.twimg.com/media/Cn9zfJuW8AAMopy.jpg – Jammin’
PFIZER Did anyone see the new Pfizer commercial explaining the whole process of drug development. For the first time a company is actually defending their industry. It is a very welcome sign that biotech realizes it needs to educate the public on all of the many factors that go into drug development and how complicated and expensive it is. ! LONG PFE
Long $PFE perennially. Suspect $PFE eyeing $INCY for buyout. Long $INCY. I also feel $TGTX (long) is a great, though somewhat early buyout candidate, possibly also by $PFE. And what $PFE isn’t eyeing, $AGN probably is (long there too).
$INCY has performed admirably since our first mention of it here.
I took some $RLYP profits in to $INCY, feeling very comfortable with the decision.
$TLOG 8K 072016 Intends to appeal de-listing; correspondence – http://hsprod.investis.com/shared/v2/irwizard/sec_item_new.jsp?epic=tetraLogic_pharmaceuticals&cik=&ipage=11045319&DSEQ=&SEQ=&SQDESC=
ALL $TLOG SEC filings: http://ir.tetralogicpharma.com/sec-filings
Have an #AwesomeWeekendAll – Jammin’
We discuss a lot of science here, and often speak of its quality or lack thereof. And yet how does one learn to gauge, to assess, to vet scientific excellence. Exposure and experience are fine teachers. One method I’ve often used is to show trainees papers that are particularly good or particularly bad, and let them calibrate their own perception of the work accordingly. Having been told it’s fine work or that it’s reprehensible work, they can then sniff out the attributes of the work that make it so.
Keep in mind, the mere fact that a paper is published means nothing as to its quality. This is because of the literally thousands of scientific journals published each month, perhaps 5 percent at best really matter and can really be counted on. The need to publish is so strident now that we even have the academic equivalent of vanity presses: journals that WILL give your paper a cursory going-over, and, oh, by the way, for a fee of $5000 will almost certainly publish it.
En route to looking up something else, I came across this paper the other day. I immediately began howling with laughter and had a hard time stopping. Here, the WORST paper I’ve seen in a long long time.
https://www.ncbi.nlm.nih.gov/pubmed/16690220
Now, ask yourself, what about this paper makes it particularly rotten?
To all:
The Komarova hypothesis was published in 2006, in the timeframe of sociobiology. One of the tenets of this field at that time was (and to some extent still is) that phenotypic expression is shaped by the actions of natural or sexual selection. That’s what Komarova is suggesting. The classic paper putting adaptationism in a more proper perspective is S. J. Gould’s “Spandrels of San Marcos”, which is easily found online. For the unfamiliar, this is a must read for understanding selection and its alternatives.
Terry
https://www.ncbi.nlm.nih.gov/pubmed/16690220
Possible duplicate post: first attempt eaten by system.
We speak often of science and of science quality here. But how does a lay reader learn what is good science and what is wretched? One method I’ve often used with people I’m training is to give them manuscripts reflecting particularly good or particularly loathsome work—–superlative papers of either stripe— and let them then figure out what makes the work so.
En route to looking up something, I stumbled upon this the other day. I must say, I howled with peals of laughter for many minutes and initially wondered if it was a joke paper such as of the kind the BMJ occasionally runs. But it’s no joke.
The link at the top is the worst paper I’ve seen in eons. Have a look. What makes it particularly rotten?
Just for starters, I have never tried to sunbath my underarms. 🙂 So..the rest of the lymph system is protected by??? As a woman, am I now at higher risk for shaving my one chin hair?
Just the very idea that hair is oncoprotective and lymphoprotective? What hooey? Hair is within which bacteria flourish! People shave for hygiene. Moreover, if this totally bogus hypothesis had any merit at all, we would be hair-endowed where our lymphoid organs are most prolific. But last time I checked no one has hair over their spleen! Indeed, the richest node distribution in the neck is cervical, where there often is no hair at all! And why have such hair on your head when the cranium lacks lymph nodes?
She wasn’t high in spirit when she came up with this scrofulous nonsense. She was high ON spirit, methinks.
And her name is Sweatlana. 🙂
DR I was just going to post the thesis that is an example of symbiosis if not serene-dippity. As is well known undergarments are often absent under the robes of camel pilots so the fleas can readily travel from camel to human thigh to the public region. After building up numbers there they are drawn to axilla by the fear o moans in natural musk. ( may also be spelled pheremones) There they also grow in number and exude
a waxy/oily substance as the result of digestive process and though crude it is a good lubricant. Bare skin on bare skin can easily chafe and hair being keratin has good wear characteristics which combined with flea feces ease the movement of the pit joint. Symbiosis is evident!!!
Serene dippity is possible. 🙂
Where do I apply for my Nobel?
Although I can’t get past the abstract— the author isn’t providing any evidence to support his theories.
It’s almost as if he’s staring up in the sky, musing about armpits, and scribbling down whatever pops into his head.
So armpit hair is ‘highly conserved.’ The Darwinian conclusion is that it must have a really important function. Hahahaha. Good luck Mr. Author.
Link click yields “Access Denied
Your access to the NCBI website at http://www.ncbi.nlm.nih.gov has been temporarily blocked due to a possible misuse/abuse situation involving your site. This is not an indication of a security issue such as a virus or attack. It could be something as simple as a run away script or learning how to better use E-utilities, http://www.ncbi.nlm.nih.gov/books/NBK25497/, for more efficient work such that your work does not impact the ability of other researchers to also use our site. To restore access and understand how to better interact with our site to avoid this in the future, please have your system administrator contact info@ncbi.nlm.nih.gov.”
BTW, I believe someone here recently spoke of a warning about the SG log-in link being identified as a likely “phishing” site. I experienced that a couple of days ago, the one time I tried to log in from my iPad.
Maybe I need to heed the advice in the current notice about “learning how to better use E-utilities” ?
That’s not anything indicating malice/virus/security/phishing issues, I’ve seen it come up before for PubMed and I suspect it’s triggered by firewalls that restrict particular traffic when they’re afraid it will overload something. I wouldn’t think we’d be likely to drive enough traffic to an individual page from Stock Gumshoe to alert their system, but perhaps it’s extra sensitive. PubMed was down for a while last month, I think, maybe they’re on a hair trigger to keep traffic under control or we triggered some sort of “alert” algorithm that blocked traffic.
v4t1 It sounds to me that something on your own computer is causing the problem. Do you have a program called E-Utilities?
Perhaps as part of a virus program. It could even be in some adware tracking what you view. Do you use more than one browser? A different browser might let you in. Security is an increasing problem and not all browsers are compatible with all websites. Sometimes running a complete scan for virus, adware,
malware etc and then rebooting will clear up problems like that.
Frank and v4t1,I’ve experienced a similar effect with the
following site: stateofthemarkets@marketfy.com.
I’ve read the daily reports from this site for years, but
within the last few months Norton Security has blocked
me from accessing this report under the auspices of ;
this site has known to have malware associated with it.
The only way I can now access it is by turning off Norton
Security. This is more than likely a bug in Norton’s program
but getting them to admit it would probably take an
“act of congress”.
Regards,
Frank
$CARA – CARA THERAPEUTICS INC COM
NASDAQ : CARAOption Chain
$6.00 1.00 (20.00%)
Bid/Ask
5.99 / 6.03
B/A Size
3,600 X 600
Volume
Long – Jammin
$CDNL – CARDINAL RESOURCES (PL)
OTC BBN : CDNLOption Chain
$0.0128 0.00 (25.49%)
Bid/Ask
0.0115 / 0.0128
B/A Size
10,000 X 198,000
Volume
5,847,633
Long and deep – FridayFeeling – Jammin’
$TRIL – $TRIL Helen Ong added,
nature @nature
CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis http://go.nature.com/29WxuhX
$SCYX – $SCYX breaks abv the major resistance on volume…the stock could now start climbing. 2.73 (50EMA) initial target https://twitter.com/ACInvestorBlog/status/756556475611295744
$MRNS News coming; high risk/high rewardInTheTrenches added,
max @LTbioinvestor
$TTPH also could bounce
$MRNS news coming (high risk high reward)
$NVLS (low valuation) InTheTrenches Retweeted max
Sgssogiam Retweeted KSS, MD, PhD
$RGLS #Weekend #read #LifeTime #changing #education #Empower #yourself #Biotechnology http://www.stockgumshoe.com/author/dr-kss-md-phd/ … #ZKSSSgssogiam added,
KSS, MD, PhD @KSSMDPhD
Coming this weekend to StockGumshoe,com: A hepatologist parses the ruction at Regulus $RGLS #RG101 #HCV
Travis, It was easier when we could write a new post at the bottom of the page after the last comment, rather than scrolling back up to the top of the comments section to do so – just a minor bit of feedback.
In other news: $TRXC has scheduled earnings call for Aug 5th, it seems. They have been quiet since the fiasco – let’s see if they have anything to add during earnings. This stock has become deadweight unless there is some fresh news. I am in the mood for a portfolio cleanup – jettisoned $OGEN and looking to clear out $BLRX soon. Giving $PARN until earnings to persuade me to hold.
This in from the CDC today: a shocking, totally alarming surge in the HCV vertical (mother to baby) transmission rate in Kentucky.
https://www.cdc.gov/mmwr/volumes/65/wr/mm6528a2.htm?s_cid=mm6528a2_w
Answer to Question of the Day:
The correct answer is a.
The rest are untrue.
Oncology drugs are phase 1’d in patients with cancer of varying types, because for oncology, phase 1 is an exploration of potential antitumor activity (which equals toxicity, in a sense). Non-oncology drugs are phase 1’d in healthy volunteers, who are generally paid well for their trouble. Onc phase 1’s are sometimes labelled phase 1/2a because of the antitumor efficacy aspect. The goal of an oncology drug is to cause toxicity to at least some cells, and therefore doing onc phase 1’s in normal “volunteers” as the Nazis did is monumentally unethical.
Nice work all. Most of you reasoned through it accurately.
#Deadline 7/27: Submit abstract for Improving #Cancer Risk Prediction for #Prevention http://the.aacr.org/eZ8m #AACRrp16 😉 https://pbs.twimg.com/media/CoAFvWEVMAEGjVm.jpg
LOVE2LOVE #ZKSS & Gummune – Jammin’ 🙂 🙂
wtf WondersThruFreedom #FF #FridayFeeling #WeekEnd 🙂 🙂 🙂
Share your #WTFs http://www.stockgumshoe.com/2016/07/microblog-w-t-f/
$RLYP, just want to send out a note of thanks to DrKSS for this one. I decided to stay long, just thought it was inevitable for a buyout at some point. The last data dump of paid scripts kept me in, they doubled from the previous month, where in months prior they were more modest. So I got about 85% profit on paper (still holding), good for about a 7% pop on my total portfolio. I’ll hang on for a couple of weeks, but thinking about accumulating some $CYDY. Saw Mark Schoenebaum of Evercore/ISI on CNBC the other day, high on Gilead for the long term. Like Doc, he notes they typically grow through acquisition, and both their HCV and HIV sales are slowly trending down. The have deep pockets, and $CYDY seems like it would be a good target for them.
I forgot, long live KSS, and the other gummies as well! Enjoy the weekend folks!
New column up at http://www.stockgumshoe.com/2016/07/the-state-of-things-ruction-at-regulus/
Please move discussion thread to space after new column. Good night all.
This thread is now closed to further comment……the circus has moved on to
http://www.stockgumshoe.com/2016/07/the-state-of-things-ruction-at-regulus/
$AMGN $BIIB $CELG $GILD $ALXN
Biotech Stocks: End of Political Risks? – RBC’s Michael Yee and team contend that biotech stocks like Amgen, Biogen, Celgene, Gilead Sciences, and Alexion Pharmaceuticals are looking past the political risks. (via Barrons)
http://blogs.barrons.com/stockstowatchtoday/2016/07/29/bioetch-stocks-the-end-of-political-risk/
Long $AMGN as of today.
This thread has been closed and the biotech discussions with Dr. KSS have moved to his new article. Dr. KSS’s most recent article can always be found on his author page here.