Comments on Steven Turner's articles RSS Syndication from SeekingAlpha.com http://seekingalpha.com/author/steven-turner/articles http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-518024 518024 Tue, 26 May 2009 12:12:42 -0400 http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-463299 463299 The truth is, since I am a physician who prescribes 'T' to hypogonadal > men is that: > 1. gels aromatize to estrogen and will decrease bio-available testosterone > after 6 months of use. > 2. Testopel under Slate Pharma raised the price of the 75mg pellet > from $12.50 to $60 each. Using 5 per month gets very expensive
3. > The 3-month Nebido does not have a flat release, but will have a > high initial blood level that triggers the same aromatization and > then the low levels persist for months. > > None work well. The best is weekly self-administered injections or > compounded non-aromatizable testosterones. Cost $25-50 per week. > > > That is the 25 year truth.]]> Tue, 14 Apr 2009 16:52:02 -0400
I am well aware of the issues you sxpeak of here as far as the long-term ineffectiveness of Testosterone replacement therapy. I have suffered from hypogonadism since my early 20s, and I have felt the effectiveness of various forms of TRT diminish within a few months of use. I wonder if a powerful aromatase injhibitor such as Arimidex can be of value in restoring a more favorable testerone- estrogen ratio -- do you have any experience with Arimidex for this purpose? Also, how much can exercise (aerobic and/or weightlifting) help to trigger more production of testosterone? Are FH and LSH levels sensitive to activity such as exercise?

Thank you in advance for your response.

S



On Jan 29 09:39 PM usdoctor wrote:

> The truth is, since I am a physician who prescribes 'T' to hypogonadal
> men is that:
> 1. gels aromatize to estrogen and will decrease bio-available testosterone
> after 6 months of use.
> 2. Testopel under Slate Pharma raised the price of the 75mg pellet
> from $12.50 to $60 each. Using 5 per month gets very expensive
3.
> The 3-month Nebido does not have a flat release, but will have a
> high initial blood level that triggers the same aromatization and
> then the low levels persist for months.
>
> None work well. The best is weekly self-administered injections or
> compounded non-aromatizable testosterones. Cost $25-50 per week.
>
>
> That is the 25 year truth.]]> http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-370571 370571 Thu, 29 Jan 2009 21:39:24 -0500 1. gels aromatize to estrogen and will decrease bio-available testosterone after 6 months of use.
2. Testopel under Slate Pharma raised the price of the 75mg pellet from $12.50 to $60 each. Using 5 per month gets very expensive
3. The 3-month Nebido does not have a flat release, but will have a high initial blood level that triggers the same aromatization and then the low levels persist for months.

None work well. The best is weekly self-administered injections or compounded non-aromatizable testosterones. Cost $25-50 per week.

That is the 25 year truth.]]> http://seekingalpha.com/article/102575-pfizer-needs-isis-more-than-isis-needs-pfizer?source=feed#comment-312753 312753 I have been patiently waiting for the results from the studies ISIS > started in 2006 to measure liver fat in patients treated with mipomersen. > Mipomersen lowers cholesterol levels in blood by blocking the movement > of fat and cholesterol out of the liver. In theory this should increase > the amount of fat in the liver which is not a desirable side effect. > For this reason ISIS intiated a study in May 2006 to specifically > examine this issue. The mipomersen liver fat study was originally > supposed to be completed in February 2008 but has been pushed back > twice and the completion date is now listed as March 2010. The company > consistently implies that the drug (contrary to its known mechanism > of action) lowers liver fat but has produced no data in humans to > support this. Pfizer knows this and, in my view, correctly passed > on mipomersen. How much is ISIS worth if mipomersen increases liver > fat? Probably less than it is trading for now. In that case its use > will be limited to those patients where the risk of increasing liver > fat outweighs the benefit of cholesterol lowering. In this case mipomersen > would essentially be an orphan drug, not the blockbuster that so > many people are wishing for.]]> Sun, 23 Nov 2008 01:45:47 -0500 Daylight


On Oct 29 02:44 PM Archie wrote:

> I have been patiently waiting for the results from the studies ISIS
> started in 2006 to measure liver fat in patients treated with mipomersen.
> Mipomersen lowers cholesterol levels in blood by blocking the movement
> of fat and cholesterol out of the liver. In theory this should increase
> the amount of fat in the liver which is not a desirable side effect.
> For this reason ISIS intiated a study in May 2006 to specifically
> examine this issue. The mipomersen liver fat study was originally
> supposed to be completed in February 2008 but has been pushed back
> twice and the completion date is now listed as March 2010. The company
> consistently implies that the drug (contrary to its known mechanism
> of action) lowers liver fat but has produced no data in humans to
> support this. Pfizer knows this and, in my view, correctly passed
> on mipomersen. How much is ISIS worth if mipomersen increases liver
> fat? Probably less than it is trading for now. In that case its use
> will be limited to those patients where the risk of increasing liver
> fat outweighs the benefit of cholesterol lowering. In this case mipomersen
> would essentially be an orphan drug, not the blockbuster that so
> many people are wishing for.]]> http://seekingalpha.com/article/102575-pfizer-needs-isis-more-than-isis-needs-pfizer?source=feed#comment-293679 293679 Wed, 29 Oct 2008 14:44:54 -0400 http://seekingalpha.com/article/82981-isis-pharmaceuticals-obesity-buster-an-enormous-finding?source=feed#comment-274143 274143 Re: Bioinvestor. Actually, big pharma invests in most promising new > platforms in a rather unique way - in a press release, with a transfer > of money, rights to regional distribution, and in exchange for a > percentage of the company they're investing in. So they do share > in the profits of the successful ventures, and they also lose their > investment in those platforms that are not viable. Even the big pharma's > were taken during dot.com bubble. > > As you correctly said, upstart biotechs must partner away early products > in order to build a revenue stream that will power growth of their > future pipeline. Most fail. Also, AMGN and DNA are now struggling > as they've picked most of the low hanging fruit. > > A non-oral form of Mipomersen will discourage its wide spread use, > but if the formulation can be produced in an extended release form > or packaged in a pen-style injection similar to AMLN's Byetta, then > this might change. > -------- > Specifically regarding Mipomersen, a reversal of plaque would be > a significant benefit and would provide ISIS with an expanded use. > Prevention of cardiac disease surgeries would be a significant savings > to the HMO system (not to mention the impact on patients and families). > > -------- > Generally regarding ISIS, they have a potential platform that applies > a new drug type to old and new disease targets. The old targets are > the most promising since these are already validated, have probably > come off patent, and are abundant. Plus, ISIS will not have to spend > much money or time on early-phase discovery or legal. Targeting PTP-1b > with small molecules for instance was tried to death by every pharma > and is the poster child for each new drug platform. The platform > for ISIS is the bull case for investing here. Mipomersen is the proof-of-principle > product. > > Toxic side effects, drug-delivery issues, competition, and production > costs are the bear points. > > Long-term, ISIS is a speculative buy - to me. IMO. > > > > > ]]> Sun, 05 Oct 2008 15:45:03 -0400
- The benefits of Mipomersen aren't the issue. The issue is the delivery mechanism. Oral drugs have a better market uptake than do injectables, at least in North America and parts of Europe.

- I don't argue that ISIS has an interesting and potentially lucrative platform. Antisense is a technology that should, in principle, work well. Delivery to the point of pain is key. ISIS also has a very strong IP position in the area, IMHO one of its best acquisition strategies.


On Jun 30 11:31 AM southshorein vestor wrote:

> Re: Bioinvestor. Actually, big pharma invests in most promising new
> platforms in a rather unique way - in a press release, with a transfer
> of money, rights to regional distribution, and in exchange for a
> percentage of the company they're investing in. So they do share
> in the profits of the successful ventures, and they also lose their
> investment in those platforms that are not viable. Even the big pharma's
> were taken during dot.com bubble.
>
> As you correctly said, upstart biotechs must partner away early products
> in order to build a revenue stream that will power growth of their
> future pipeline. Most fail. Also, AMGN and DNA are now struggling
> as they've picked most of the low hanging fruit.
>
> A non-oral form of Mipomersen will discourage its wide spread use,
> but if the formulation can be produced in an extended release form
> or packaged in a pen-style injection similar to AMLN's Byetta, then
> this might change.
> --------
> Specifically regarding Mipomersen, a reversal of plaque would be
> a significant benefit and would provide ISIS with an expanded use.
> Prevention of cardiac disease surgeries would be a significant savings
> to the HMO system (not to mention the impact on patients and families).
>
> --------
> Generally regarding ISIS, they have a potential platform that applies
> a new drug type to old and new disease targets. The old targets are
> the most promising since these are already validated, have probably
> come off patent, and are abundant. Plus, ISIS will not have to spend
> much money or time on early-phase discovery or legal. Targeting PTP-1b
> with small molecules for instance was tried to death by every pharma
> and is the poster child for each new drug platform. The platform
> for ISIS is the bull case for investing here. Mipomersen is the proof-of-principle
> product.
>
> Toxic side effects, drug-delivery issues, competition, and production
> costs are the bear points.
>
> Long-term, ISIS is a speculative buy - to me. IMO.
>
>
>
>
> ]]> http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-202646 202646 Thu, 10 Jul 2008 21:00:44 -0400 ]]> http://seekingalpha.com/article/82981-isis-pharmaceuticals-obesity-buster-an-enormous-finding?source=feed#comment-195933 195933 Mon, 30 Jun 2008 11:31:16 -0400
As you correctly said, upstart biotechs must partner away early products in order to build a revenue stream that will power growth of their future pipeline. Most fail. Also, AMGN and DNA are now struggling as they've picked most of the low hanging fruit.

A non-oral form of Mipomersen will discourage its wide spread use, but if the formulation can be produced in an extended release form or packaged in a pen-style injection similar to AMLN's Byetta, then this might change.
--------
Specifically regarding Mipomersen, a reversal of plaque would be a significant benefit and would provide ISIS with an expanded use. Prevention of cardiac disease surgeries would be a significant savings to the HMO system (not to mention the impact on patients and families).
--------
Generally regarding ISIS, they have a potential platform that applies a new drug type to old and new disease targets. The old targets are the most promising since these are already validated, have probably come off patent, and are abundant. Plus, ISIS will not have to spend much money or time on early-phase discovery or legal. Targeting PTP-1b with small molecules for instance was tried to death by every pharma and is the poster child for each new drug platform. The platform for ISIS is the bull case for investing here. Mipomersen is the proof-of-principle product.

Toxic side effects, drug-delivery issues, competition, and production costs are the bear points.

Long-term, ISIS is a speculative buy - to me. IMO.





]]> http://seekingalpha.com/article/82981-isis-pharmaceuticals-obesity-buster-an-enormous-finding?source=feed#comment-194905 194905 Sat, 28 Jun 2008 18:22:40 -0400
A non-oral form of a drug will be an impediment to its widespread acceptance. In the obesity market, not too far from ISIS in Southern California, one finds Arena Pharmaceuticals. Arena (ARNA) has an oral anti-obesity drug that's currently in phase III. To date, its safety profile looks good; however, until the Phase III results are published, there is risk associated with investing in this company.]]> http://seekingalpha.com/article/82981-isis-pharmaceuticals-obesity-buster-an-enormous-finding?source=feed#comment-194386 194386 Fri, 27 Jun 2008 14:20:06 -0400
If I could get reversal with no adverse side effects, I'd give it a "shot."]]> http://seekingalpha.com/article/82981-isis-pharmaceuticals-obesity-buster-an-enormous-finding?source=feed#comment-194346 194346 Fri, 27 Jun 2008 13:22:15 -0400 http://seekingalpha.com/article/82981-isis-pharmaceuticals-obesity-buster-an-enormous-finding?source=feed#comment-194143 194143 Fri, 27 Jun 2008 10:49:02 -0400
Since it is not the individual drug that will make a start-up or the investment in one have great potential but rather the ability to bring many new drugs forward, then it is important to assess the platform more than the individual drug.

With that said, companies like ISIS, and to a lesser extent MNTA, stand today at the forefront of a new "platform" for drug discovery and the strength of each remains to be be seen.

My specific comments are:

1) Mipomersen is an injectable (not oral) preparation. Thus, the ability to expand its market share to Lipitor-like sales could be held back until ISIS launches an oral formulation. It is my understanding that ISIS intends to pursue this, but that doesn't mean it will be easy, cheap, and/or safe. Competition from generic statins should make marketing shy of attempting to expand here unless the clinical data shows benefits not seen in the statins in general. Perhaps the efficacy in reducing the plaque as stated in your blog will offer cardiologists a new tool used prior to arterial stents and/or bypass surgery.

The counter argument (a positive) would be that a once per month injection would be preferable to the patient over taking 3 pills a day, every day, along with 3 or 5 other daily medications. This would increase patient compliance. And since many seniors already visit their doctor/HMO frequently, then an injectable formulation might not be black-listed by the HMO's/insurance co's because of increased office visits per patient.

2) Bayer brought to market (thus passed the FDA clinical trials) the anti-cholesterol drug Baycol, which was later recalled for toxic side effects. Baycol was highly bioavailable (meaning it could be found throughout much of the body's tissues) whereas all of the other statin drugs including Lipitor were retained in the liver. Retaining the drug in the liver prevents the toxic side effects of sterol inhibition elsewhere in the body. As yet, it is unclear if ISIS can effectively produce an oral formulation that is retained by the liver (for Mipomersen) or the reverse, if their formulation technology can be engineered to make other potential drugs highly bioavailable (as they might need to be).

Thus, can ISIS make oral formulations that are tailored to the needs of the tissue target? This has implication as to how successful the ISIS platform will be - not just how Mipomersen can be advanced or its use expanded.

Having demonstrated proof-of-concept with Mipomersen and many of the patents in the area is a good sign, though.

Just my 2 cents,]]> http://seekingalpha.com/article/82981-isis-pharmaceuticals-obesity-buster-an-enormous-finding?source=feed#comment-194059 194059 Fri, 27 Jun 2008 09:39:17 -0400
Preclinical studies have emphasised that peripheral action is mainly what contributes to the anti-diabetic effects of PTP1b inhibition while central inhibition is what's needed for the effects on bodyweight.

Genaera appears to be the only other company with a clinical PTP1b inhibitor and it is a small-molecule central and peripheral inhibitor. It is currently in Phase 1 trials with both an anti-obesity and an anti-diabetes IND]]> http://seekingalpha.com/article/82981-isis-pharmaceuticals-obesity-buster-an-enormous-finding?source=feed#comment-193965 193965 Fri, 27 Jun 2008 08:25:35 -0400 http://seekingalpha.com/article/79452-pfizers-celebrex-mass-tort-madness?source=feed#comment-189964 189964 Sun, 22 Jun 2008 03:11:58 -0400 http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-186918 186918 Tue, 17 Jun 2008 07:16:02 -0400 study. The safety issues are benign and well known therefore there
is no need for a new study.]]> http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-185265 185265 Fri, 13 Jun 2008 18:29:27 -0400 http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-181375 181375 Sun, 08 Jun 2008 13:50:27 -0400 Pellet - most invasive requires surgery. The FDA approved an operation as it is safer than an injection?

Gels - least invasive daily applications with fluctuation even when they remember to apply everyday. The FDA approved self medication over medical supervision?

What does Europe and the 70 countries worldwide who administer long-acting depot formulation understand that the FDA does not?
Low testosterone has huge medical, financial, social and emotional costs:
diabetes
coronary artery disease
hypothyroidism
hyperlipidemia.
increased body fat
poor concentration and memory
reduced bone and muscle mass
diminished libido
erectile dysfunction
decreased physical performance

The FDA wants to impose a 2 year delay because improper injection caused reversible shortness of breath and coughing?

Excellent to read the FDA’s integrity is being questioned not just by congressional hearings but by the public for which they suppose to serve and protect!
]]> http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-180686 180686 Fri, 06 Jun 2008 21:30:42 -0400
]]> http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-180594 180594 Fri, 06 Jun 2008 16:36:30 -0400 http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-180526 180526 Fri, 06 Jun 2008 14:48:55 -0400 "The implant procedure consists of a small incision through which a trocar and cannula are inserted. The pellets are inserted through the cannula, and then the cannula is withdrawn. The incision is then closed with a Steri-Strip, and pressure is applied until bleeding stops, and the area is then covered with a dressing. We have not had any major problems in terms of side effects from this procedure. Some expertise is required in terms of placing the pellets so that underlying structures are not traumatized." Quote from the excellent website Human Health Solutions. (www.humanhealthsolutio...)
I feel that a medicine that involves a surgical procedure to take is not the same as one that can be given with an injection; that is why I did not include the scantly used Testopel in my article. Thank you all for your comments and allowing me to clarify my article.]]> http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-180252 180252 Fri, 06 Jun 2008 09:16:09 -0400
The FDA, by design, exercises extreme caution with respect to their evaluation and approval of drugs since the health of every American is potentially at risk. Additionally, their judgment is devoid of the commercial zeal that investors have about a particular product. If we had to shoulder the responsibility of evaluating a drug and observing the consequences of prematurely approving a drug that should have had a more rigorous screening, I truly believe that most would err on the side of caution.

There are presently testosterone products that are available that are delivered through safer delivery systems (i.e. transdermally). What I would be more concerned with is the potential that androgen therapy has for increased risk of benign enlargement of the prostate or that it may promote the growth of existing cancer of the prostate. However, the once every three month injectable regimen does confer a patient-centric advantage in terms of convenience.

Although the indication for Nebido is for hypogonadism (Common effects of hypogonadism include decreased sexual desire, erectile dysfunction, muscle loss and weakness, depression, as well as an increased risk of osteoporosis), the name Nebido suggests that its primary function will be to elevate the libido in men. I do believe that the phosphodiesterases (e.g. Viagra, Levitra and Cialis) will still maintain their market preeminence and support by physicians since they have specificity for the primary problem associated with erectile dysfunction (ED) without the potential of increasing the risk associated with androgens.

If the parent company continues on its track of developing innovative compounds, it is likely that a large pharma or biotech company will either partner with them or enter into some equity agreement.

Ciao,
]]> http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-179799 179799 Thu, 05 Jun 2008 13:39:45 -0400 http://seekingalpha.com/article/80164-indevus-pharmaceuticals-nebido-has-lost-its-libido?source=feed#comment-179711 179711 Thu, 05 Jun 2008 11:34:14 -0400
Seriously, what else could it be? I'm 66 yrs old and wish there was something available to deter the muscle loss I'm experiencing form low testosterone.

I'm waiting for the CEO of IDEV to make a comment on this.

I do hold stock in IDEV.

]]> http://seekingalpha.com/article/79452-pfizers-celebrex-mass-tort-madness?source=feed#comment-179576 179576 Thu, 05 Jun 2008 08:51:23 -0400
Precisely right. From a safety perspective, I'd take Celebrex any day over aspirin.]]> http://seekingalpha.com/article/79452-pfizers-celebrex-mass-tort-madness?source=feed#comment-177566 177566 Sun, 01 Jun 2008 13:20:02 -0400 http://seekingalpha.com/article/79452-pfizers-celebrex-mass-tort-madness?source=feed#comment-177513 177513 Sun, 01 Jun 2008 10:54:37 -0400 http://seekingalpha.com/article/79452-pfizers-celebrex-mass-tort-madness?source=feed#comment-177339 177339 Sat, 31 May 2008 14:57:24 -0400 2. I find it ironic that your description of "greed" fails to include the CEOs of these companies who get paid hundreds of millions, often through deferred payment plans and other shifty ways - are they cockroaches or beetles?
3. Lawyers fill in the void of government regulation.
The question is who is going to make sure massive corporations are not abusing their power and distributing useless or dangerous products - either lawyers or the government. You choose

Me thinks you are jealous of lawyer salaries? Why don't you vent out your frustration at overpaid corporate managers?]]> http://seekingalpha.com/article/79452-pfizers-celebrex-mass-tort-madness?source=feed#comment-177308 177308 Sat, 31 May 2008 13:33:29 -0400 http://seekingalpha.com/article/79452-pfizers-celebrex-mass-tort-madness?source=feed#comment-177203 177203 Sat, 31 May 2008 09:14:11 -0400