Is anyone else on here a Doctor or Biomedical researcher (etc)?, page-9

Great to hear from you @imback. Thanks for posting your thoughts.

[Off-topic: At some down the track, I'd like to get your thoughts about the Netflix documentary: "Bleeding Edge"]

My concern is the potential for OPT-302 to cause glaucoma, for two reasons:

- VEGF-C is required for lymphangiogenesis of Schlemm's Canal, in adult eyes. VEGF-C is required for the development, proliferation and growth of Schlemm Canal's endothelial cells. Poor outflow of aqueous humour through Schlemm's Canal is a significant risk factor for the development of glaucoma (slowly progressive, irreversible blindness). In contrast, the PRESENCE of VEGF-A impairs aqueous outflow. (Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153703)

- Whilst anti-VEGF-A/B [ranibizumab] and anti-VEGF-C [opt-302] drugs have a similar effect on chorioretinal angiogenesis, they appear to have OPPOSITE effects on intraocular pressure. Using an anti-VEGF A or A/B agent will likely promote a normal IOP, but using an anti-VEGF C agent will likely promote an IOP rise.

- As it is, when the current standard of care is provided (a 0.05ml intravitreal injection of anti-VEGF-A/B), repeated IOP spikes occur in the short term, on a background of a slight elevation in long-term IOP. The current standard of care is enough to reduce retinal perfusion at the macula and induce glaucomatous cupping. (Reference: https://www.retina-specialist.com/article/what-octa-reveals-about-macular-perfusion)

- We've established that the current standard of care promotes glaucoma. I'll give you one guess as to what happens in the long term when you:

a) Use a medication (opt-302) which inhibits the growth factor (VEGF-C) responsible for the development, proliferation and growth of the main pathway for aqueous humour to exit out of the eye (Schlemm's Canal) (Ref: See 1st reference)

b) Inject twice as much liquid inside the eye at each visit (0.05ml + 0.05ml = 0.1ml), compared with the current standard of care (0.05ml). (Reference: https://clinicaltrials.gov/ct2/show/study/NCT03345082)

24 weeks of follow-up is not long enough to know whether the patients would develop glaucoma from the treatment. Again, they're not presenting a scientific publication here: it's not even clear whether they were even monitoring for signs of glaucoma at all.

I have other concerns with what is presented:

This "new data" (11 Oct) is not scientific literature, and they make it very hard to determine the statistically significant results within the presentation.They promote the efficacy of OPT-302 against PCV which they state is "The predominant form of wet AMD in Asian populations" (ref: OPT announcement 11 Oct 2019), yet, of the 366 patients recruited into the study, the PCV subgroup was only n=22. Why? Because they "white-washed" their study recruitment: Only 13 out of the 366 patients they recruited were NOT caucasian. (ref: OPT announcement 11 Oct 2019: slides)

Bravo, Ophthea.

A sample size of 22 is underpowered in anyone's book.

Finally, nobody but Genentech will consider investing in OPT. All we know is the effect of combining OPT-302 with Lucentis. We do not know how OPT-302 would perform on its own. We also do not know how it would perform if it were combined with Eylea.

The data we have is for a fairly narrow set of circumstances.It would be really interesting to see 2y outcome data for the patients in this phase 2b trial, if they continued on the Q4/52 Rx (of 0.1ml of Lucentis+OPT-302) regimen for 2y or longer. Particularly interested in the patient's IOP and progression of glaucomatous visual field defects - and how many are dependent on one or more glaucoma medications, etc (or have needed glaucoma filtration surgery since starting treatment with OPT-302)

Looking forward to discussing this. Please use proper scientific evidence, and please refrain from discussing the share price / financial side here...it would be nice to keep this thread as exclusively about the biological / pharmacological topics, if possible.

Cheers
jaykay