FDA Doings: Always in the Crosshairs

Doc Gumshoe looks at the drug and device approval process

By Michael Jorrin, "Doc Gumshoe", February 19, 2014

[Ed note: Following is another installment from our favorite medical scribe, “Doc Gumshoe” (no, he’s not a doctor). We feature Michael’s commentary every couple weeks or so, and his thoughts and words are his own. “Doc” doesn’t pick stocks, but FDA decisions are a huge driver of investment success for pharmaceutical and biotech companies and today Michael does some explaining about how the FDA and clinical trials work.]

Readers of this blog have a pretty wide range of opinions about the FDA, although the more outspoken of you mostly chime in with negative comments. Doc Gumshoe, being aware of the many stark conflicts between the FDA and drug companies, is a skeptic regarding the view that the FDA is in cahoots with Big Pharma. But this little piece looks at a few areas where the FDA’s recent practices have been subject to criticism from elevated sources. Before I go on to cite chapter and verse, I should recap some of the specific hurdles that the drug and device approval process has to leap over.

What does a treatment have to demonstrate to gain FDA approval?

The answer, in two words (plus a conjunction) is efficacy and safety. That goes for any intervention, whether it’s a drug or a device or any other kind of treatment. But how can that be demonstrated? If we’re talking about a drug, the gold standard is the randomized, placebo-controlled clinical trial, in which the candidate drug demonstrates at least some advantage over an existing drug. The advantage could be with regard to any of several parameters – a greater percentage of patients attaining a specific marker, a more rapid onset of action or a longer duration of action, a lower incidence of adverse effects, and a number of others. And this advantage needs to be statistically significant, meaning that the results of the clinical trial must be highly unlikely to have been a matter of chance.

There are lots of obstacles that the pharma company has to overcome. Here are just a few:

If there are already some fairly effective existing drugs for a disease, it’s likely to be difficult to enroll patients in a trial where the patient would not know whether he/she was going to get the existing drug, or a placebo, or a new experimental drug.

If the trial calls for patients/subjects who have never taken a drug for that disease or condition – drug-naïve patients, as they are known – it may be exceedingly difficult to recruit enough patients for the kind of big Phase 3 trials the FDA likes to see. Patients newly diagnosed with a disease or disorder want to be treated with a drug that is known to work.

Then there’s the issue of diseases/disorders/conditions that don’t affect large numbers of people. Again, in such cases, it may be difficult or impossible for drug companies to enroll enough patients for multiple clinical trials.

For those reasons (and others) lots of trials are now being conducted in the so-called “less developed” parts of the world, and sometimes, perhaps, with less rigorous standards than would be expected.

… and, of course, there’s another issue …

Namely, how long it takes for some drugs to get approved and available for treatment. We all remember the early days of the AIDS epidemic. When there was something like a promising drug coming along, there was intense pressure to get that drug to people who were dying of AIDS. That got a lot of publicity, and the FDA got it in the neck for being “obstructionist” – that is, for insisting on going through the time-consuming approval process.

The FDA, to some degree, initiated changes in their procedures – mostly a matter of streamlining the bureaucracy and simplifying procedures.

But in response to the clear need to speed things along – get drugs to the patients who need them – the FDA has also instituted some changes in the requirements for approval, specifically for some medical conditions, based on such issues as limited availability of treatment options and urgency of getting some kind of treatment to patients who might have rapidly deteriorating illnesses.

“Breakthrough Therapy Designation,” or BTD

Here’s a statement directly from the FDA:

Fact Sheet: Breakthrough Therapies

On July 9, 2012 the Food and Drug Administration Safety and Innovation Act (FDASIA) was signed. FDASIA Section 902 provides for a new designation – Breakthrough Therapy Designation. A breakthrough therapy is a drug:

  • intended alone or in combination with one or more other drugs to treat a serious or life threatening disease or condition and
  • preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

If a drug is designated as breakthrough therapy, FDA will expedite the development and review of such drug. All requests for breakthrough therapy designation will be reviewed within 60 days of receipt, and FDA will either grant or deny the request.

Please refer to section 902 of FDASIA for more specific information about this provision. Additionally, a draft Guidance for Industry: Expedited Programs for Serious Conditions––Drugs and Biologics was published on June 25, 2013, and includes information such as qualifying criteria for breakthrough therapy designation, features of the breakthrough therapy program, and guidelines on how to submit a breakthrough therapy designation request.

As of the beginning of 2014, the FDA had received over 100 breakthrough therapy designation (BTD) requests and approved only about 30%. They declined about 60% and another 10% or so are currently pending.

Some of the “winners” are:

  • Gazyva (obinutuzumab), developed by Genentech (Roche), for chronic lymphocytic leukemia (CLL) in combination with chlorambucil. CLL is not a rare disease. Indeed it’s the most common form of leukemia, and in some patients it progresses so slowly that it may be reasonable not to treat at all. However, there are more rapidly-progressing variants that warrant more aggressive treatment, and Gazyva’s promise is that it will be less toxic than some of the current combined therapies.
  • Imbruvica (ibrutinib), developed by Janssen and Pharmacyclics (Johnson & Johnson), for mantle cell lymphoma, a genuinely rare form of cancer for which effective treatments options have been lacking.
  • Sovaldi (sofosbuvir), from Gilead, for hepatitis C. The advantage here is that it allows for treatment without interferon. Treatment with interferon may need to continue for a year, with nasty side effects, and the cure rate with Sovaldi approaches 100%.

So those are a few successes for BTD, approved in near-record time. However, this supposed pathway to earlier drug approval has not by any means been the bonanza the pharmaceutical industry was hoping for. The majority of the new drug applications still need to go the slow way, and the slow way is still slow.

But the FDA is also getting criticized for being too lax!

A JAMA paper (Downing NS et al, “Clinical trial evidence supporting FDA approval of novel therapeutic agents 2005 – 2012,” JAMA 2014;311(4):368-377), published a few weeks ago, examined the basis on which new drug treatments were approved by the FDA between 2005 and 2012. A total of 188 new drugs were approved, for 206 indications. These approvals were based on 448 so-called “pivotal” trials, meaning relatively large Phase 3 trials. However, the investigators reported several findings of concern:

  • Of the 188 new drug approvals, 74 were based on the results of a single pivotal trial.
  • 91 – almost half – were based on surrogate end points rather than on clinical evidence of improvement in the patients’ disease or disorder. And an additional 36 were based on scores on tests used to measure the impact of a disorder, such as depression or cognition. Only 67 were based on clinical outcomes.
  • Only about 40% of the trials compared the new agent with an existing drug; the rest compared the new agent only with placebo.

Granting approval to a drug based on a single trial might be justified based on the importance of making the drug available to patients for whom other options are significantly less effective, or if there are impediments in mounting another large Phase 3 trial – i.e., difficulty in recruiting patients.. However, a fundamental scientific principle is that results of experiments – and a clinical trial is definitely an experiment – have got to be able to be replicated. The history of science is rife with examples of experiments that could not be replicated: some of us may remember the announcement that scientists had been able to achieve “cold nuclear fusion” – a pipe dream that has never been replicated. A single Phase 3 trial is all very well, but don’t we want more evidence than that?

A “surrogate end point” is an easily-assessed measurement of some parameter that stands in for the real clinical goal of the treatment being evaluated. Employing surrogate end points might be justified on the basis of pure practicality. For example, a frequent surrogate end point in trials of cancer drugs is measuring tumor size. If the tumor shrinks, the drug is assumed to be working. There’s an obvious problem with waiting for the more definitive end point, that being the disappearance of the tumor, or alternatively, the death of the patient. But tumors have been known to shrink and grow again, so it may be somewhat premature to approve a drug for widespread use based on that particular surrogate end point.

Similarly, lowering blood pressure and lowering cholesterol are surrogate end points for lowering the risk of heart disease, and by and large the evidence is convincing that in patients who are at significant heart disease risk, lowering those parameters does seem to translate into decreased heart disease mortality. However, we need to remember that for a very long time after cholesterol had been fingered as the culprit in atherosclerosis, all of the experiments to determine whether lowering cholesterol actually conferred a survival benefit were inconclusive – yes, the interventions lowered cholesterol, but it made no difference in patient survival. It was only in 1994, with the Scandinavian Simvastatin Survival Study, that a clear and definitive survival benefit was seen. But that survival benefit, quite clear in “at risk” patients, is not so clear in the general population.

Finally, failing to conduct clinical trials where the new agent is compared head-to-head with an existing agent, and instead comparing the new agent only with placebo, is definitely the preference of the pharmaceutical companies, but not likely to be in the public interest. One could see how the pharma outfits would prefer trials where their new drug is compared with placebo rather than with an existing drug which is known to be safe and effective. In a trial versus an existing drug, they might come in second, and that would be curtains, while in a trial versus placebo, they have at least a chance to try to spin the results in the most positive light. But from the patients’ perspective, the comparison with the existing agent is clearly the more valuable information.

The JAMA paper is not about the breakthrough drug designation, which only got underway at the very end of the period covered in the paper. But it points at the underlying tension between two (at least two!) high priorities – one, to make sure that drugs approved by the FDA are indeed safe and effective, and two, to make sure that patients who can benefit from these drugs don’t languish in their illness for an unnecessarily long time.

By the way, breakthrough drug designation is not the same as orphan drug designation, which gives pharmaceutical companies incentives to develop drugs for diseases which affect fewer than 200,000 persons – so-called “orphan diseases.” The objective of BTD is getting drugs to patients quickly, of the orphan drug designation, developing drugs for treatment areas where the pharmaceutical companies may not have big financial incentives.

So, how do we arrive at a procedure that addresses both issues?

What The Celebrated Man (or Woman) In The Street (T. C. MITS / WITS, as he/she were referred to in some excellent books I read in my early youth) wants and needs is reliable assurance from High Places that the drug he/she needs is definitely okay. But at the same time MITS and WITS want the drug when they need it, and not five years later. So what’s to be done?

Doc Gumshoe’s answer is, make the drug available, but tell MITS/WITS “here’s what we know about it so far,” with emphasis is on “so far.” The drug developer and the FDA have got to keep gathering data (which they’re absolutely supposed to do – it’s called “post-marketing surveillance”), and the FDA needs to keep reviewing the status of any drug that was granted approval based on less than the usual standard. Yes, if the results of that single Phase 3 trial versus placebo warrant it, approve the drug, but require further data, and keep a watchful eye on that drug.

T. C. MITS/WITS should understand that FDA drug approval does not constitute the untarnishable Gold Star that forever guarantees that the drug is safe and effective. It just means that based on the available evidence to date, the FDA considers that it’s okay to prescribe the drug to patients who need it. For example, the FDA would not approve some drugs, such as cancer drugs that have toxicities, for the treatment of hay fever. (That doesn’t mean that physicians might not prescribe it for hay fever, or for any other condition – that’s called “off-label prescribing,” and physicians are permitted to do it. However, if a patient has a bad adverse effect due to off-label prescribing, the pharmaceutical company is off the hook, and the physician bears the entire responsibility.)

But the FDA needs to be more assiduous about demanding and evaluating data after drug approval, and needs to be proactive about getting further information to the public – healthcare providers and patients alike.

And, on another issue, FDA approval of medical devices …

Evaluating the efficacy and safety of medical devices might appear to be a good deal simpler. After all, it either works or doesn’t work, and it either harms the patient or it doesn’t, right? But there are inherent complications. Device manufacturers adopt complex (and expensive) stratagems to come up with “dummy” devices that look like the real devices, but don’t do anything, so as to mimic the placebo arm of a drug trial. That works sometimes. But if the device is something like a heart valve, or an artificial hip, dummy devices are out of the question.

So lots of devices are approved on the basis of observed probable effectiveness, and this is particularly the case when the patient population for whom this device is intended is fairly small. A case in point is a device, the BSD-2000 (made by BSD Medical in Salt Lake City), that employs microwaves to raise the body temperature in cancer patients, which supposedly makes cancer cells more susceptible to radiation therapy. It was originally developed to treat patients with advanced cervical cancers that did not respond to other treatments, but has since been used “off-label” to treat other cancers.

Devices of this type can be quite expensive – the BSD-2000 runs half a million dollars – and this obviously creates a considerable incentive for facilities that own such devices to use them, perhaps off label. And because there is an FDA provision called “humanitarian device exemption” that applies to devices for disorders affecting fewer than 4000 patients, allowing for approval to be granted based on a presumption of effectiveness, which opens the door for more widespread use of devices, perhaps for conditions other than those for which they were originally approved.

Does relaxing the approval process in this way provide a benefit to some patients? Clearly, yes! But does it perhaps also open the door to abuse? Perhaps so. We know that when medical facilities invest in some imaging devices, it’s hard to get out the door without being scanned. Pain in your pinky? Into the MRI!

And a warning about “FDA Warnings”

A valued reader sent a link to a site with the scary headline “20 Drugs You Should Not Be On!” This was based on FDA warnings in the prescribing information (PI) for those drugs. Here’s the list, with a brief summary of the warnings:

A 2007 federal law requires the FDA to disclose all its investigations into reports of possibly drug-related adverse events. The first of this series of quarterly reports has been released. It includes adverse events reported between January 1 and March 31, 2008.

Here’s the list of drugs and the adverse events that have been reported:

Arginine Hydrochloride Injection (R-Gene 10) — Pediatric overdose due to labeling and packaging confusion
Desflurane (Suprane) — Cardiac arrest
Duloxetine (Cymbalta) — Urinary retention
Etravirine (Intelence) — Hemarthrosis (blood in a joint)
Fluorouracil Cream (Carac) and Ketoconazole Cream (Kuric) — Adverse events due to name confusion
Heparin — Anaphylactic-type (life-threatening allergic) reactions
Icodextrin (Extraneal) — Hypoglycemia (low blood sugar)
Insulin U-500 (Humulin R) — Dosing confusion
Ivermectin (Stromectol) and Warfarin — Drug interaction
Lapatinib (Tykerb) — Hepatotoxicity (liver toxicity)
Lenalidomide (Revlimid) — Stevens-Johnson syndrome (a deadly drug reaction)
Natalizumab (Tysabri) — Skin melanomas (deadly skin cancer)
Nitroglycerin (Nitrostat) — Overdose due to labeling confusion
Octreotide Acetate Depot (Sandostatin LAR) — Ileus (bowels not moving)
Oxycodone Hydrochloride Controlled-Release (OxyContin) — Drug misuse, abuse, and overdose
Perflutren Lipid Microsphere (Definity) — Cardiopulmonary reactions (lung/heart problems)
Phenytoin Injection (Dilantin) — Purple glove syndrome (discoloration, pain, and swelling of the hand that may lead to amputation)
Quetiapine (Seroquel) — Overdose due to sample pack labeling confusion
Tebivudine (Tyzeka) — Peripheral neuropathy (tingling or numbness in the extremities)
Tumor Necrosis Factor (TNF) Blockers — Cancers in children and young adults

Are those warnings real? Yes indeed. But do they mean that “you should not be on those drugs?” For most patients, the warnings don’t mean anything more than “be careful,” which one should always be when taking drugs of any kind. To rule out nitroglycerin due to “labelling confusion” would deprive huge numbers of people with angina from very safe and highly effective relief – and likely consign them to more invasive treatment. To rule out fluorouracil and ketoconazole because of confusion between Carac and Kuric is dopey! Should diabetics be deprived of Humulin because of the possibility of dosing confusion? Well, I won’t go on.

The scoop on FDA warnings is that there’s hardly a single drug in the entire Physician’s Desk Reference, which contains all the PIs for all FDA approved drugs, that doesn’t include a warning. There are always warnings. That doesn’t mean we don’t have to take them seriously, but it also doesn’t mean that we have to run screaming in the opposite direction.

* * * * * * *

Thank you for all the comments; keep them coming! By now, hardly anyone hasn’t heard about the big retrospective study that concluded that mammograms don’t result in any survival benefit. I’ll have quite a lot more to say about that, but for now, I will just take a few shots:

  • One, it’s a 25 year retrospective study, employing radiographic techniques back to the mid-1980s.
  • Two, it excluded ductal carcinoma in situ (DCIS), on the grounds that those cancers “rarely need treatment.” DCIS cannot be detected by manual breast examination, and a significant percentage of these cancers do eventually become invasive.
  • Three, a conclusion was that mammograms resulted in overdiagnosis, and “unnecessary treatment” of about one in three diagnosed cancers.

But how does anyone know whether it’s necessary to treat the cancer, unless and until the patient dies of some other cause?

Best to all, Michael Jorrin (aka Doc Gumshoe)


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63 Comments on "FDA Doings: Always in the Crosshairs"

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susan levy
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susan levy
February 19, 2014 10:47 am
I served on an IRB at a medical school for 22 years as a voting, non physician on approval for drug and device studies within the university. What you did not address in your article is the % of drugs approved that 5 years later have to be recalled due to unanticipated side effects not seen in the studies. This give reason to pause before taking a drug that requires either long term use or has not been on the market for more than 5 years…. Integrative healthcare, using natural solutions before committing to rx drugs for years or a… Read more »
welchtt
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welchtt
February 20, 2014 2:42 pm
Our household rule of thumb is 10 years on the market, to see those results. That and to ask for a copy of the studies. But that is how we think, and have taken the time to investigate our approach to our healthcare. The integrative healthcare is very exciting, in my opinion, despite the allopathic reluctance. On the flip side, we have a senior parent, 2-pack a day non-filter smoker, cachectic non-compliant diabetic, who just wants a pill to enable him in his habits. Any talk of making changes to improve his health is considered by him to be “high… Read more »
abot100
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abot100
February 19, 2014 10:58 am

Does Doc Gumshoe have an opinion on Nanoviricides (NNVC) that can share with us?

Solyom
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Solyom
February 19, 2014 11:00 am
As a neurologist and unpaid volunteer at a free medical clinic, I have always been amazed that patients do not bring bottles of ALL medications (herbs, OTC, Prescriptions) they are taking, that they do not have a WRITTEN list of questions to ask their doctor that physicians do not have long detailed questionaires for them to fill out that physicians do not require the keeping of seizure calendars. headache calendars and do not provide lists of reading materials to be found at the local library concerning their illness and sites on the internet that provide good information. The situation seems… Read more »
susan levy
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susan levy
February 20, 2014 11:26 am

agreed. Did some research on why patients don’t tell their doctors what they are on or what they eat. THey fear ridicule and of course the mentality promoted in this country is ‘Just take a pill for this, that and everything”. We all need to be reminded to keep a log of symptoms because so many are vague and we just pass them off it becomes a chore as well. Does not remove the value though.

kuczynski
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kuczynski
February 19, 2014 11:23 am

which health system is better … the “socialistic” ie canadian or “capitalistic” ie american system?
supposedly there is a waiting list for treatment in canada for non-emergency treatment … how many people per 100000 die waiting for treatment?
in the us, people that cannot afford treatment die … how many per 100000 die because they can’t afford treatment?
now, doesn’t it make sense that the system with the lower deaths per capita is the better system? the next question … why hasn’t someone looked into this?
henry

Rusty Brown in Canada
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Rusty Brown in Canada
February 19, 2014 12:18 pm
Don’t believe all you hear about wait times in Canada. I know of a case where a guy in a small town went to his doctor for a routine checkup on the 4th of the month. She sent him to a nearby cardiologist the next week, who rigged him up with a 24-hour blood pressure monitor, and he got the results the next day when he took the rig back. The cardiologist scheduled a thorough workover at a major clinic, including ultrasound and treadmill test a week or so later, and finally a full angiogram in a major hospital in… Read more »
susan levy
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susan levy
February 20, 2014 11:27 am

I heard same kind of tale ten years ago. All this hype to keep medicine so profitable it bankrupts our nation. Canada is on a better track in this arena for a long time.

aaiken
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aaiken
February 22, 2014 10:27 am

Canada does have the longest wait times in the OECD for non-emergency treatment. Also, in many cases, the formulary available to physicians is sharply limited.
From a comparative health standpoint, Netherlands has a better health system than Canadain terms of outcomes, and much more patient freedom.
Unfortunately, Obamacare has taken the US away from the Dutch example, rather than toward it.

Dr. KSS MD PhD
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karmaswimswami
February 22, 2014 4:51 pm
Andrew: One of the great unspoken problems with the US healthcare system Iand since I am a provider in it I feel I have a right to say something) is this: it has been decades since Americans doctors did, first and foremost, what is best for their patients. American doctors look at a patient’s situation, and diffract care through the lens of what is best for them. Doctors do above all else what is best for themselves, and if the patient is an incidental beneficiary, then so be it. Until we completely remove a doctor’s ability to make a decision… Read more »
welchtt
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welchtt
February 24, 2014 11:12 am

We do have that system, the Veteran’s Administration. The exception that keeps it from being identical to what you are saying, is that the surgeons get periodic bonuses. I have about 10 years in the system, and 2 locations. It’s not the picture of efficiency.

sophie1
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sophie1
February 19, 2014 11:35 am

I would also like the Doc’s take on (NNVC) Nanoviricides. It would seem that having a viricidal panacea from bubonic plague to bird flue that is easily administered for some of the world’s deadliest viruses are on the cusp of availability, but still no approval activity. Is this the fault of our FDA, or the company?

David B.
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February 19, 2014 11:43 am

The U. S. healthcare system is currently the worst system that money can buy. In other words, we have the most expensive system by far in the developed world with just about the worst outcomes, especially for the bottom 50% of the population in terms of income. Of course if one is wealthy the outcomes are good. There are many studies that back this up–don’t take my word for it. It’s a shame that all attempts at reforms tend to get shot down by big money interests.

joshsorensen
Member
0
February 19, 2014 3:49 pm

David – you should say the middle lower class has the worst outcomes in the US. If you are extremely poor, you get Medicaid and several other entitlements, which basically enable you to live for free. Granted, this is not living in luxury but it is free. The lower middle class are the ones who are struggling to get by and the wealth distribution in the US is outlandish…

Rusty Brown in Canada
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Rusty Brown in Canada
February 19, 2014 12:01 pm

I sure agree with the statement calling nitroglycerin “…very safe and highly effective relief…”
Amen to that! I avoid prescription meds as much as possible, but don’t touch my nitro! As they say “it tastes terrible and it works!”.

Dr. KSS MD PhD
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karmaswimswami
February 19, 2014 12:16 pm

We have discussed Nanoviricides at length in another thread here. Very difficult for me to envisage agents that sequester and partition viruses but do nothing to alter replication in cells will have a great role in medicine.

arch1
Irregular
5283
February 19, 2014 1:47 pm

Doctor KSS. D o you think NNVC approach has possibility of vaccine to prevent virus from entering cell? I must admit ignorance on my part on how that could be possible. Thank you for your generosity, as I think many are in my position.

Dr. KSS MD PhD
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karmaswimswami
February 21, 2014 10:19 am
Frank: I really don’t think NNVC can accomplish that. Their method does nothing to the immune system. It cannot prime the immune system to prevent a virus or go more fitfully after a virus. The best a NNVC drug might do is be given after a known exposure so as to attenuate the course of a viral illness. I am interested in learning what their clinical studies show eventually, but conceptually I have real doubts that this approach is going to make a huge difference. It is an analogy I have used before: neuraminidase inhibitors such as Tamiflu nominally do… Read more »
gumshoegabby
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gumshoegabby
February 20, 2014 11:03 am

You may want to take a look at Inovio Pharmaseuticals INO, if you’re interested in getting behind a promising company in the field of vaccines that introduce synthetic DNA to enhance your own immune system to address cancers and viruses, etc.
http://seekingalpha.com/article/2032351-the-real-inovio-pharmaceuticals-an-interview-with-dr-j-joseph-kim-ceo?source=yahoo

jonken
Irregular
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jonken
February 20, 2014 12:36 pm

To “GumshoeGabby”: I was looking at INOs message board today. A question was asked and when I left it had still not been addressed. Here it is: Why no Phase III studies? If that’s true then I AM really curious and reluctant to invest. Please tell me your thoughts on this. Many thanks.

mmenkhaus
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mmenkhaus
April 1, 2014 9:34 pm
To Ken Meyer – No Phase III studies yet because their Phase II study doesn’t issue results until mid 2014. You MUST complete Phase II before Phase III because the phases build on each other to determine 1. Safety 2. Efficacy 3. Optimal dosing 4. Side Effects Also, because side effects may only manifest in a very small percentage of patients, each phase includes larger populations – that helps to identify infrequent side effects. Hope this helps. BTW, I like INO; as a pharmacist, I understand most of the technologies they are attempting to employ and to date, it sounds… Read more »
arch1
Irregular
5283
February 19, 2014 1:16 pm

IMHO re. NNVC; I held for a long time because their concept seemed promising,however they seem to me to be more concerned with company officers & board of directors compensation than bringing product to market. Last straw was what seemed to me dilution of stock. I really hope they eventually turn a profit & would happily reinvest if that came about. My record on timing is dismal, stock may be ready to soar.

et69
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et69
February 19, 2014 1:26 pm
How one views the FDA is pretty much like asking ,”Is the glass half full or half empty ? ” That said, we can see corporate influence in all venues of government not just the FDA. Personally I don’t think there is any question that corporations influence the FDA, its just a matter of and to what degree. When I see capitalist, profit motivated corporations “loaning” large amounts of their employees to the FDA to “facilitate” their review process , well, it can’t bode well for integrity and objectivity. There cannot be but a conflict of interest. If ever there… Read more »
michelg
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michelg
February 19, 2014 1:34 pm

Rusty: I believe you’re thinking of Buckley’s cough syrup… 😀

Rusty Brown in Canada
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Rusty Brown in Canada
February 19, 2014 9:44 pm

Thank you. I was hoping someone out
there would get my little in-joke.
RB

arch1
Irregular
5283
February 19, 2014 1:58 pm

IMHO ; I think which system worst/best is subjective to personal biases. My view has been most problems are self-inflicted and we have unwarranted expectation of magic panacea. If you survive the first two years of life & are reasonably responsible in self-preservation I think most would get 50 to 70 years of life without much outside help. Of course because of increasing defects creeping into human genome, what I said is increasingly untrue.

kuczynski
Irregular
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kuczynski
February 19, 2014 2:39 pm

yes, but isn’t it in society’s best interest to have healthy citizens? having said that, the system that yields the greatest number per capita has to be the undisputed winner!

arch1
Irregular
5283
February 19, 2014 2:53 pm

Henry I think you are absolutely correct. However isn’t definition of “Healthy’ also somewhat subjective? I am often wrong & I do appreciate if I can be shown where so I can correct self. Experience has made me wary of ‘isms & ists” Re. capitalist/socialist etc. : makes me think perhaps some unfounded belief system present in rabid believers. I mean no implication of you as one.

kuczynski
Irregular
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kuczynski
February 19, 2014 9:08 pm
frank, i’m just a believer in facts not ideology … and am curious about the “health system debate”, as i’m sure everyone else is as well … and yes, “healthy” is difficult to ascertain and my definition may be different than someone else’s … but we can all agree on death and that minimizing the per capita death rate should be in everyone’s interest, n’est pas? thusly, i’m of the opinion that the best “system” is the one with the lowest mortality rate, has to be the better one … yes, we all also want a high quality of life,… Read more »
arch1
Irregular
5283
February 20, 2014 7:44 am

Henry; we have no dis-agreement & I meant none. I am a firm believer that we all have much to learn from the others view point & so I was hoping to elicit further comment from you. I think that opinion is a necessity , the rub is that there is so much that is absent basis & that’s why we need the the interplay of thought and discussion. BTW part of my heritage is Slavic; Czech As most Americans are ,an increasingly complex mix.

Alan Harris
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Alan Harris
February 19, 2014 3:38 pm
Thanks Doc. I knew zip about the FDA process. I now know 1% which is a vast improvement. Trouble is we/they appear to be ‘chancing’ with lives by saying anything definative without 100% certainty …definative = liable. I dont think Doc’s/FDA are liable if they say nothing and just let people die while waiting for that Utopia drug. It may already exist, but cant be reco’ed coz its not 100% certain in the case of Joe Blow. The problem will never be fixed unless Docs/FDA are allowed to issue some sort of disclaimer along the lines ‘We did our best!’… Read more »
Michael Jorrin,
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Michael Jorrin (aka Doc Gumshoe)
February 19, 2014 4:51 pm
I don’t know much about NanoViricides as a company, nor yet how their mechanism of action differs from that of other antivirals. My guess is that the “nano” part of their name is an attempt to capitalize on the buzz around nanotechnology. It’s pretty easy to kill viruses up until they actually invade our cells. After that, the trick is to attack the virus without harming the cell where it has gone to live and multiply. The most successful means have been to interfere with viral replication in some way, without, of course, having a bad effect on the capacity… Read more »
gumshoegabby
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gumshoegabby
February 20, 2014 11:12 am

If we could enhancement our own immune system we stand a better chance of natural success and IMO Inovio is on the cutting edge of doing so.

mmenkhaus
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0
mmenkhaus
April 1, 2014 9:41 pm

gumshoegabby: I agree; the most successful antiviral therapy is immunizations; the problem is how to help the body find the right antigens! INO appears to be on that track.

Sam
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Sam
February 19, 2014 8:14 pm

This request is to Mr. Gumshoe not to Dr. Gumshoe.

I think, Louis Navellier is at it again with three Biotech Doublers. The first one is very easy. I guessed it after reading first three lines that it is Chinese Sinovac (SVA). However, along with many others we would appreciate if you advise us on the other two.

Thanks.

xcernfsi
Member
22
xcernfsi
February 20, 2014 1:21 pm

Nice run-up recently in Benitec (mentioned by karma swim swami back in November) – any guesses on a catalyst? Trial results leaking, or takeover rumors?

xcernfsi
Member
22
xcernfsi
February 20, 2014 1:24 pm

and I see that the Hep-C trial is still in the enrollment stage, so that’s not it.

tanglewood
Irregular
170
February 20, 2014 4:35 pm

Hi David,
Are you aware of this other Gumshoe thread that has had lots of discussion about Benitec.
http://www.stockgumshoe.com/reviews/biotech-supertrader/this-tiny-unknown-biotech-is-about-to-unleash-its-holy-grail-drug/#comment

xcernfsi
Member
22
xcernfsi
February 21, 2014 12:13 pm

Hi Tanglewood – I’d done a search and looked at the original November mention of Benitec, missing all the back and forth in the thread you’ve just linked to – I’d forgotten about that mega-thread after reading it when Travis brought it up on the main posting a little while back. Thanks for putting it back in front of me, and sorry for fragmenting the discourse. And thanks karma for the updates here, and there.

Dr. KSS MD PhD
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karmaswimswami
February 21, 2014 10:40 am
David: “Enrollment” is an unfortunate term for these trials to use. I am sure both sites have all the patients picked out. Once the FDA greenlighted the study, those patients had to be called in, be thoroughly lab screened (baseline labs of all kinds, including testing for AAV8 antibody), and subjected to baseline liver biopsy. This takes time. Also, since Benitec’s work in macaques with TT-034 has long since been completed, my guess is that once the FDA authorized initiation of the study, they actually had to manufacture TT-034. Making viruses for pharmaceutical purposes is much more complex than making… Read more »
Dr. KSS MD PhD
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karmaswimswami
February 21, 2014 10:41 am

I said macaques. I meant cynomolgus monkeys.

garlandlink
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garlandlink
February 24, 2014 3:49 pm

Awesome advice on Benitec (BNIKF)! Bought a month ago and it is doing great! This is my first investment based on Gumshoe recommendations. Glad that I joined! Besides being a penny stock, does anyone see any downside to BNIKF?
Thanks,

Rusty Brown in Canada
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Rusty Brown in Canada
February 24, 2014 4:10 pm

“Gumshoe recommendations…” !?
Really? Gumshoe is now “recommending” investments?
I doubt it severely.

Dr. KSS MD PhD
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karmaswimswami
February 21, 2014 10:27 am
David, no, no NEW takeover rumors. Many wonder if Pfizer will re-attain its senses and be interested again in the company. What I feel has happened in the last 48 hours is US buying of BNIKF responding to ASX buying of BLT (which is the obverse of what has driven share appreciation in recent weeks). Investors in Australia are catching on that this may be a great company and so buying there is now showing parity with buy orders in the US. It is the only ddRNAi company (other ddRNAi players except Gradalis license from Benitec, and Gradalis will likely… Read more »
playonwords
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0
February 21, 2014 11:20 am

Thanks karmaswimswamee I took your advice on Benitec a few weeks ago and have more than doubled my money.

c193
Member
54
c193
February 20, 2014 1:59 pm

I too bought some Benitec due to its mention here. This is my first foray into a penny stock. Do most of you sell or hold in this type situation? Are we seeing a trading range developing or a lasting increase? The original poster said he thought value would be achieved next year if IRC.

Dr. KSS MD PhD
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karmaswimswami
February 21, 2014 10:27 am

Cindy: please hold. Or buy more. Don’t sell. Things are just getting interesting.

Sam
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Sam
February 22, 2014 10:14 am
Cindy, Just because there is ‘F’ at the end of symbol doesn’t mean it is a Penny Stock. ‘F’ at the end means it is a foreign stock. There are many good foreign stocks those don’t have formal ADR trade on Penny Stock Market. You would be surprized to see that there are many good foreign stocks are with ‘F’ at the end; and unless you have an agent who can buy foreign stocks directly you don’t have a choice but to by the stock with ‘F’ in USA. By the way, you must have found that you have to… Read more »
who noze
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0
February 21, 2014 5:38 am
im a 88yr’old timer w// a drug problem i had some lunge removed[ca]] who now has abreathing problem ive been uing SPRRIVA BUT NOW HAS TO USE teDORZA DUE TO HEALTH PLAN SUBSTITUTION TROUBLEis that tedorza needs a deep brath to activatei dont have the brath required so its useless my dr says its doubtful and rquires a great deal of work to get an approval for spiriva incidently spiriva is $145 per monthvs 15 prior to removal from the approved list there a little more to the story but i dont want to bore you i i was just… Read more »
Dr. KSS MD PhD
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karmaswimswami
February 21, 2014 10:32 am

Who Noze: Is there some reason you couldn’t just go back to Atrovent? Or use atropine via a home nebulizer? I can certainly see where Tedorza would be a problem for you. Why did you have lung resection? For cancer or as a COPD mgmt strategy? Are you on an inhaled beta-2 agonist (albuterol, formoterol)?

microcapwiz
Member
2
microcapwiz
February 21, 2014 9:55 am

Theralase (tltff) and tlt-canada) anyone heard about them. mkt seems incredible
He PERSONALLY endorses and uses this technology in his rehab clinics and facilities.

Here is also a great article from ESPN that details the life and career of Dr. Andrews:

http://sports.espn.go.com/espn/news/story?id=3024046

“Andrews has been on the cutting edge of new surgical technologies and rehab techniques that enable players to play longer and recover from injuries faster.”

Read more at http://www.stockhouse.com/companies/bullboard/v.tlt/theralase-technologies-inc#jI9eP3zhqxzyEm9g.99

who noze
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February 21, 2014 10:51 am

had ca spoke to my gp who didnt know of any other uitable drug though i was on servent for awhile

Rusty Brown in Canada
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Rusty Brown in Canada
February 21, 2014 1:55 pm

ca? cardiac arrest?

Dr. KSS MD PhD
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karmaswimswami
February 21, 2014 11:02 am

Who Noze: Serevent is a long-acting beta2 agonist. I feel that you need to be on both an anticholinergic (Atrovent, Spiriva, or home-nebulized albuterol) PLUS an inhaled beta2 agonist (albuterol or formoterol). You need both medicines to have relief and control. Your case is complex, and might be best managed by a pulmonologist, as I am guessing you have at least GOLD stage III COPD if not IV. You need to avoid use of inhaled steroids if at all possible given the lung cancer history, which I am sorry to hear about.

who noze
Guest
0
February 21, 2014 11:19 am
the 2nd part of this soorry tale is thati had tedora for the irst time with a detailed pamphjlet on how to use tez-= nowhere does it say u need a deep brath to activate it does say to go bach p[33 five and repeat operation if that fails see your DR.which i did we both agreed that mechanism was defective so bck to phar.who sayhs see mfr. so i oder new one and that too failed now im out 30 bucks in the meantime im trying to speak to someone at forest phar.w// 15 diff. numbers none of which… Read more »
who noze
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0
February 21, 2014 11:26 am

problem is that sireva is an out of pcket expense to 145 per month and i am seeing a pulmonary doc have to make an appt. thanks for responding to my tale of woe hopefully it cud helpsomeone passing y

Michael Jorrin,
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Michael Jorrin (aka Doc Gumshoe)
February 21, 2014 6:21 pm
Not being an MD, and having incomplete knowledge of Who Noze, I’m highly reluctant to make treatment recommendations, but I agree with KSS on several points. A pulmonologist may be able to help in several ways, not only by prescribing appropriate drugs, but perhaps also with respiratory therapy that may make your breathing somewhat easier. I have done some work in COPD, and know of good results with shorter acting beta agonists (emphasis on shorter acting), as well as with anticholinergic agents based on atropine IAtrovent). Both of these classes of agents attempt to counteract natural mechanisms in our bodies… Read more »
Dr. KSS MD PhD
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karmaswimswami
February 21, 2014 7:18 pm
Who Noze: Your lung resection could be a vague blessing in disguise as regards COPD simply because this surgery does cause lung tissue to regenerate and when it does so, it does so without the tendency for air trapping, the loss of airway elasticity, that typify COPD. Inhaled agents like Spiriva and Atrovent have anticholinergic effects that fundamentally help limit secretions. Beta 2 agonists act as dilators of bronchi and bronchioles. You need a long acting beta 2 such as formoterol, but need to have on hand a quick onset one such as albuterol for exacerbations. Do you need O2?… Read more »
who noze
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0
February 21, 2014 8:47 pm

THANKS TO ALL W/ SEE A PULMONARY PHYS SHORTLY STOPPED SMOKING 20 YRS AGO

vivian lewis
Guest
0
February 23, 2014 7:24 pm
Oz stocks ending with the letter F are trading in the USA; the F stands for foreign. They should be purchasable in a normal brokerage account because they are trading on the pink sheets or in the grey market. They are “penny stocks” because in Australia lots of shares trade in their pennies, which convert into an even smaller number of our pennies. If your broker is hitting you with a $50 fee for buying Benitec, or any other US traded Australian stock you should change brokers. Beyond that I know nothing about the shares at issue. The following do… Read more »
revsusi
Member
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revsusi
March 11, 2014 1:22 pm

Another FDA question. Scancell has just received Orphan Drug Status on one of its drugs. What does that mean, in terms of the future, trials, approvals, etc?

Michael Jorrin,
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Michael Jorrin (aka Doc Gumshoe)
March 11, 2014 6:35 pm
I’m not familiar with Scancell or its drug that got orphan drug status – I’ll check. But what this designation is about is that pharma companies used to hesitate before investing large amounts in developing drugs for diseases/conditions that affected relatively few people – no money in it, they thought. All that has changed. Now drugs for diseases with fewer than 200,000 affected US patients get several boosts – tax breaks, FDA approvals based on smaller trials, longer patent protection, overall more lenient treatment from regulators, compared with drugs with a lot of competitors and a huge market. Also, there… Read more »
Susan Graham
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Susan Graham
March 11, 2014 7:35 pm

Scancell is listed as SCLP on the AIM market in London. It has had some success on a vaccine for melanoma, and on ways to deliver other vaccines, but I don’t understand enough of the science to know more than that. Investors feel it is near to a break-through in the treatment of a variety of cancers, and that it is positioning itself to be bought by a big pharma company. I think they thought Merck was interested. Thanks for explaining the orphan drug status for me.

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