Some drugs are actually more effective at lower doses.
Lucentis is more effective at 0,5 mg than at 2 mg (HARBOR study)
The point is -- you don't need to get a lot of drug in there if it's a potent drug.
If I can throw in my two cents, I think Singerman is drawing a distinction between therapeutic levels of squalamine reaching the back of the eye -- which now seems pretty certain — and how potent the squalamine is once it gets back there (to be determined by the clinical trial data).
Livermore believes squalamine will be highly effective and safely produce vision gains beyond those produced by Lucentis and Eylea. I have been thinking along the lines of squalamine being more suitable as a maintenance therapy.
I thinl Singerman is hedging a bit (and he probably should be to avoid leaking clinical data). I think he is saying that squalamine has proved it can get to the back of the eye (a big achievement) but he is not speculating on the level of potency it delivers.
By the way, I think a peer-reviewed, bylined article in RP mentioning squalamine in depth shows a level of seriousness that the retina community is now attributing to squalamine. I think before the Elman and BP presentations squalamine was looked upon as an curiousity.
Well, it's a bylined article so they were willing to put their name on what they assert. The Elman case study is covered in the news section.
Interesting to me that IPOs for investigational eye drug companies have become smoking hot -- OPHT, AERI and EBIO all have soared recently.
I think the interest has heated up because investors are looking for the next REGN or the next OHRP.
I know many of you who post on this board just want to hear about OHRP -- but it looks like the eye drug arena has become a "sector" of its own for those who like to cast a wider net.
Maybe we will see an eye drug ETF soon.
OPHT just laid out its drug development plans for the next couple of years -- of course, it is all intravitreal injections and their combinations require two injections (which I consider a big drawback if they can't change that).
As an approved maintenance therapy the stock value would be much above where it is today. I can't be specific.I don't like to throw numbers around.
It is a big deal -- and a big hurdle has been overcome.
In the single case Dr. Elman reported on, there was no improvement in VA but the patient was 20/25 at baseline -- pretty good baseline vision.
I am still leaning to squalamine as maintenance but we've already argued this point ad infinitum.
I would say overall market is overextended and needs a rest.
Don't see many bargains right now.
One thing the Elman study does for OHRP is that the company went from being an oddity to a serious contender. That's a pretty big leap based on one case.
Could be but I can't see retina docs just saying "go home and self administer this."
I still see it as complementary -- but what's wrong with that?
Not true. I was consistently a proponent of squalamine as a maintenance drug.
Skeptic that it going to be the dominant retinal drug.
Here's that article on the seven-year patients. I just found it in RP archives.
A fascinating study that brought back 65 patients who participated in two of the earliest trials for Lucentis after seven years demonstrates a wide range of visual outcomes for these individuals, many of whom are now in their mid-80s. The study will be presented at the upcoming ARVO meeting in early May. Thus, this article will not go into specific detailed findings of the report.
The study, called Seven/Up and led by Robert B. Bhisitkul, MD, of the Department of Ophthalmology, University of California at San Francisco, involves patents who were originally enrolled in Genentech's pivotal ANCHOR and MARINA trials in 2003 and 2004. The 65 patients were part of a group that was then followed through the HORIZON extension study.
Once this cohort of early Lucentis patients was identified last year, they were re-evaluated with a complete battery of tests for retinal disease, including the most up-to-date SDOCT imaging.
What the researchers found was that at seven to eight years removed from their initial Lucentis injections, the patients could be divided into several distinct subgroups ranging from good vision (20/40 or better) and durable CNV quiescence, to a larger group with poor vision (20/200 or worse) and ongoing exudative disease activity. There were even several instances of patients who were legally blind (20/200 or worse in both eyes).
The researchers concluded that with these earliest Lucentis patients, clinical vigilance and prolonged treatment may be required in some patients for seven years or longer.
I remember reading an article about some of the earliest ANCHOR and MARINA patients who were on Lucentis for seven years.
Of course, being an elderly cohort, the number of people still on Lucentis shrunk pretty dramatically as the years went by.
If I remember right, those who stayed on Lucentis a long time fell into two major and distinct groups -- the ones who were still getting some benefit and the ones who were getting little or no benefit.
I think we have to recognize that wet AMD is a somewhat individual disease in that people with certain complement (genetic) factors are much more disposed to get it and that the various therapies show great differences in effectiveness in different types of patients.
Even the Glaxo drug (pazopanib) dosed orally had a subset of responders who shared a certain genetic makeup.
Therapies are getting more personalized and customized -- this is where drug researcrh is headed in a big way.
As far as recognizing that anti-VEGF triggers GA -- don't sell the retina docs short. Rosenfeld and Patricia D'Amore and others have been on this for a long time. But for the time being, you can't just stop using anti-VEGF drugs. However, the warning that Rosenfeld is sounding is that they musty be used cautiously.
If -- and it's a big if — squalamine can be used safely and effectively with a vast majority of retinal disease patients, the current therapeutic landscape is wide open for such a drug to take a huge place.
AF may be trying to preserve his credibility.
It's like the department store Santa says to the little kid:
"Have you been good this year?"
And the kid says back:
One man's "small" may be another man's "significant."
AF minimizes the use of the word "Regression" in the Elman study.
If the title had used the word "Failure" or "Non-effectiveness" wouldn't that be seen as a significant clue to the study's results.
AF did a good job debunking Ampio's extravagant claims -- but almost anyone with knowledge of the retinal space could have done that. OHRP is a different kettle of fish.
If the Elman paper is positive on squalamine, which the title seems to indicate, it will move the stock up.
He could look pretty bad if the Elman paper is positive -- which the title of the paper indicates.
Any role for squalamine is a win. That would be a more realistic expectation.
The Elman paper is the next big event.
It will be closely scrutinized -- even if it is just one patient.
(an option straddle would be a nice play if OHRP had options)
I am still seeing squalmine's role as complementary therapy. And what's wrong with that?