New Delhi: Suggesting that the protocol title and phase should be revised for India, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organization (CDSCO) has given its nod to pharmaceutical major Roche for conducting the study of Ophthalmic drug Faricimab.
However, the approval is subject to condition to revise the study title Phase IIIb in place of IIIb/IV. In addition, the expert panel directed that the randomization of the subject should be competitive and more subjects should be randomized.
This came after the firm presented its proposal for Phase IIIb/IV clinical study protocol number MR43808, version 1.0 dated 27-Jan-2022 before the committee.
Faricimab is an IgG1-derived bispecific antibody against VEGF-A and Ang-2 for the treatment of age-related macular degeneration and diabetic macular oedema.
The retina is largely avascular to facilitate effective photoreceptor function; instead, the retina is fed by both retinal and choroidal capillary networks, pathologies of which result in retinal and choroidal vascular diseases such as diabetic macular oedema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO).
One of the underlying causes of retinal vascular diseases (RVDs) is retinal neovascularization (NV), the aberrant growth of new vasculature, usually due to sustained retinal ischemia and mediated primarily by vascular endothelial growth factor A (VEGF-A).VEGF-A is a VEGF family member, which also includes VEGF-B, -C, and -D, whose members signal through the VEGF receptors (VEGFRs) VEGFR-1, -2, and -3 to mediate endothelial and lymphatic growth.
Faricimab is a bispecific antibody (bsAb) based on human IgG1 comprising two heavy and two light chains capable of simultaneously binding to both VEGF-A and Ang-2 produced using the “CrossMab” platform.
Faricimab binds VEGF-A and Ang-2 with binding affinities (KD) of approximately 3 and 22 nM, respectively; importantly, faricimab does not detectably bind Ang-1.Faricimab Fc region has been modified to reduce binding to FcγR and FcRn receptors. The former virtually eliminates immune-mediated functions such as antibody- and complement-dependent cytotoxicity and antibody-dependent phagocytosis, whereas the latter increases faricimab systemic clearance by reducing FcRn-mediated IgG recycling.3 Thus, faricimab works by depleting both VEGF-A and Ang-2 to prevent retinal NV in the privileged ophthalmic environment.
At the recent SEC meeting for Ophthalmology held on November 25th 2022, the expert panel reviewed the proposal for Phase IIIb/IV clinical study protocol (number MR43808) of the Ophthalmic drug Faricimab.
After detailed deliberation, the committee recommended the proposed study with the following conditions:
1. The protocol title and phase should be revised for India and the study title should be Phase IIIb rather than IIIb/IV. Accordingly, the applicant should submit India specific protocol addendum with the respective study title & phase of the trial.
2. The randomization of the subject should be competitive and more subjects should be randomized.