L10, Lucentis/Eyelea injections only work for 2 years, correct? Why? Will Squalamine work indefinitely? And...
L10, Lucentis/Eyelea injections only work for 2 years, correct? Why? What happens to the wet AMD patients who have had the injections for two years and does their disease start progressing again? Will Squalamine work indefinitely? And is it possible that the wet AMD patients who have been getting the injections and have to stop after 2 years, could use the squalamine drops and see regression in their disease because of a different MOA? Thanks
my understanding from the angiogenesis conference is that from years 3 thru 5 visual acuity starts to degrade because of geographic atrophy. and after 5 years, vision is as bad or worse than when treatment began. as i mentioned, retina specialists just comprehending how bad GA complication is. not many patients on these drugs for 5+years yet, but as that milestone passes, more aware of issues.
since squalamine does not cause GA, it should be a preferential therapy for lesser cases or younger patients or even most patients as a place to start with rescue shots as a follow on. no mater what, retina specialists will need to manage number up shots downward from fear of GA. this alone, would make even a less efficacious squalamine a valuable option. a more efficacious drug and we have a category killer.
does this sound right Livermore? i am just a stock jockey w no science background.
Thanks, rxonman, it appears L10 agrees with you. It's hard to refute that squalamine drops should be the gold standard for ALL patients with any type of neo vascular proliferation disease of the eye. And like you said, even if at first it turns out that the retina specialists are skeptical, they will have to try squalamine to reduce the number of injections to reduce GA. Once they start using squalamine drops, the docs will quickly recognize it works as a safer monotherapy. And by the time the drug is approved, there will be a lot more data that shows squalamine to be more efficacious and safer than the current VEGF injections and docs will be eager to use it. And the whole dry AMD market will open up because of the safety. The fundamentals are so clearly positive. And now we know the drug gets into the human choroid and penetrates well enough to work in an even tougher disease (PDR) than wet AMD. Of course, we already new that squalamine worked from the Genaera IV treatments and now we know it "sticks" in the choroid long enough to be effective. Like L10 says, it will work in the vast majority of patients in wet AMD. And like L10 says, where else is there such a high return investment with such a low risk. Just need to be disciplined enough to sit tight.
yes your completely right rxonman and that is the biggest reason why squalamine should be preferentially used in younger patients. Actually squalamine drops should be used first line in all choroidal neovascular lesions in all patients.
The retinal docs are still slow to comprehend the link between anti-vegf and GA. There is just so much reticence to admit that the current standard of care is actually accelerating vision loss in other parts of the retina that are under most oxidative stress. The retina docs seem to lack the understanding of how feedback loops work. There is a purpose to having a baseline level of vegf.
It will take the large phase 3 squaalmine eye drops study that is being planned that compares squalamine to antivegf treatment that will show conclusive evidence that the GA is being worsened by antivegf (whereas the squalamine patients will not have increaed GA). Only then I believe will the retinal docs understand the connection
I think the vision improvement in the real world studies of Lucentis have shown that vision improvement is back to baseline after 2 yeas. So the patients gain on average a few letters but then lose this gain by the 24 months. This is better than losing 15 to 20 letters if they were not being treated.
As to why they lose letters, there are a few reasons. For instance, by not blocking pdgf or bFG, the lesions are not eradicated in many people, or the leson changes it's growth patter to have more pericytes and fibroblasts instead.
Also the concentration of anti-vegf fluctuates dramatically between dosing, thus allowing micro leaks to develop which mechanically disrupt the RPE, perhaphs leading to the loss of vision
Squalamine drops should have none of these problems and I expect much better retention of vision gains
currently the retina docs say the reason for losing the vision after such long treatment periods is due to the slow progression of the dry amd that causes atrophy in the retina, that can not be treated. But this is definitely true that the vision goes down acutely after about 24 months