Lengthy, and interesting, presentation of the RGX-314 (anti -VEGF-fAb gene therapy) (RGNX).
regenxbio.gcs-web.com
While, presenters tried hard to present strong case for this approach, several missing points and facts deteriorate overall impression (which was good).
~250ng/ml 6-month fAb expression level looks ok (dosed at 6 x 10e10 vg) , but to call this "lifetime trend" (IF it is for 6 months it is MUCH LONGER????) is way too HYPE.
Anyway, iv Lucentis has much larger max Abs concentration (but not very good 4w-end level): <Although vitreous concentrations of ranibizumab declined in a monoexponential fashion with a half-life of 2.88 days, concentrations of >0.1 µg/ml ranibizumab were maintained in the vitreous humor for 29 days. Ranibizumab concentrations in the aqueous humor of the injected eye reached a peak concentration of 17.9 µg/ml, 3 days after drug administration. Elimination of ranibizumab from the aqueous humor paralleled that found in the vitreous humor, with a half-life value of 2.84 days. No ranibizumab was detected in the serum or the fellow eye.>
sciencedirect.com
They have room to increase expression level, with 4-th and 5-th cohort.
Also, flat CRT and sudden large (+10 letters) improvement in BCVA (3 subjects, cohort 3) indicate that subjects were (while active on first Lucentis iv) one who are not responding well, long term. Regardless very large injections numbers in pre-treatment period (30-35 injections, 4-5 years), So, those subjects were one who have decline in BCVA by 8-10 letters, my speculation, from baseline (when Lucentis therapy started). We do not have history of those subjects (RGNX does), but my view is that those are subjects that should not have further severe vision loos on anti-vegf therapy. Company presented delta-value, but not absolute letters value.
Gene insertion level in sub-retinal space is something that should be fairly quantificated. Lucentis or anti-VEGF-Fab is not the best choice (even if continuously and at significant level present in aqueous humor), and would be interesting to compare expression data for ADVM-022 (when intravitreally gene delivery therapy from ADVM is presented on aflibercept, starting dose 6 x 10e12 vg).
clinicaltrials.gov
finance.yahoo.com
<The vector was designed with the purpose of improved transduction efficiency to the retina when administered intravitreally. > So far none confirmed this as case in human.
Pre-clinical publication:
cell.com |
