1. Color Vision and Microperimetry Changes in Nonexudative Age-Related Macular Degeneration After Risuteganib Treatment: Exploratory Endpoints in a Multicenter Phase 2a Double-Masked, Randomized, Sham-Controlled, Crossover Clinical Trial
Julie A Kornfield, Melvin A Sarayba, Hampar L Karageozian, Peter K Kaiser, Lisa S Karageozian, Janine M Aubel, Eleonora M Lad, Hugo Quiroz-Mercado, Baruch D Kuppermann, Vicken H Karageozian, David S Boyer, Jeffrey S Heier Ophthalmic Surg Lasers Imaging Retina . 2022 Aug;53(8):430-438. doi: 10.3928/23258160-20220725-02.
Background and objective:To explore the association between best-corrected visual acuity (BCVA) improvement and changes in microperimetry (MP) and color vision in patients with nonexudative age-related macular degeneration following administration of two 1.0-mg intravitreal doses of risuteganib.Patients and methods:In a phase 2a, prospective, double-masked, sham-controlled study, eyes with nonexudative age-related macular degeneration and Early Treatment Diabetic Retinopathy Study BCVA between 20/40 and 20/200 were randomized to intravitreal risuteganib (1.0 mg) or sham injection. The risuteganib group received a second 1.0-mg dose, and patients in the sham group crossed over to receive 1.0 mg of risuteganib at week 16. Exploratory endpoints included changes in color vision and mesopic MP.Results:Thirty-nine patients (risuteganib,n= 25; sham,n= 14) completed the study. There was a significant (P< .05) correlation between BCVA and the total error score (TES) for both Lanthony and Hue Style. Confusion index was close to the criterion for significance (P= .056) in the risuteganib group. All color vision metrics demonstrated a trend toward improvement in risuteganib responders (BCVA letter gain ≥8 letters) and no change in the nonresponders, with significant differences seen in confusion index between the risuteganib and control group (P= .0493) and between responders and nonresponders (P= .0478). MP showed that risuteganib responders improved in mean sensitivity and change in number of loci ≤11 dB and ≤0 dB, whereas nonresponders worsened.Conclusion:All color vision and MP parameters tested trended toward improvement in risuteganib-treated patients and risuteganib responders. Statistically significant improvement was evident in two metrics: confusion index (in risuteganib-treated patients and responders) and number of loci with decreased sensitivity (in responders). A significant correlation between BCVA and both TES Lanthony and TES Hue Style in risuteganib patients provides concurrent evidence of objective and subjective improvement of retinal function.[Ophthalmic Surg Lasers Imaging Retina2022;53:430-438.].
2. Emerging Therapies in Nonexudative Age-Related Macular Degeneration in 2020
Arshad M Khanani, Sumit Randhir Singh, Jay Chhablani, Anindya Samanta, Aamir A Aziz, Mahima Jhingan Asia Pac J Ophthalmol (Phila) . 2021 Jan 28;10(4):408-416. doi: 10.1097/APO.0000000000000355.
Age-related macular degeneration (AMD) is one of the most common causes of severe vision loss in the developed world. Advanced forms of AMD are seen in primarily 2 types, exudative AMD involving the presence of choroidal neovascularization and nonexudative or dry AMD with geographic atrophy. For the latter, the combination of vitamins and minerals known as the Age-Related Eye Disease Study-2 formulation has been shown to decrease the rate of progression of nonexudative to exudative AMD, as no other treatments are currently approved for nonexudative AMD. This review will highlight upcoming treatments for nonexudative AMD. Six upcoming agents have shown results at least in the 2A phase. This includes intravitreal agents that are inhibitors of integrin (Risuteganib), intravitreal agents that disrupt the complement pathway (Zimura, APL-2), neuroprotective implants (Brimonidine DDS), a subcutaneous injectable (Elamipretide), and photobiomodulation (Valeda Light Delivery System).
3. Risuteganib-a novel integrin inhibitor for the treatment of non-exudative (dry) age-related macular degeneration and diabetic macular edema
Seenu M Hariprasad, Prisha Jain, Reanna Shah, Ravi Nayak, Lincoln T Shaw, Anna Mackin, Siona Jain Expert Opin Investig Drugs . 2020 Jun;29(6):547-554. doi: 10.1080/13543784.2020.1763953.
Introduction:Non-exudative (dry) age-related macular degeneration (AMD) and diabetic macular edema (DME) are leading causes of vision loss worldwide. Besides age-related eye disease study (AREDS) vitamin supplements, there are no efficacious pharmaceutical interventions for dry AMD available. While numerous pharmacologics are available to treat diabetic macular edema (DME), many patients respond suboptimally to existing therapies. Risuteganib is a novel anti-integrin peptide that targets the multiple integrin heterodimers involved in the pathophysiology of dry AMD and DME. Inhibiting these selected integrin heterodimers may benefit patients with these conditions.Areas covered:This article offers a brief overview of current pharmaceuticals available for dry AMD and DME. The proposed role of integrins in AMD and DME is reviewed and later, risuteganib, a novel anti-integrin peptide is introduced. The data from initial Phase 1 and Phase 2 risuteganib clinical trials are discussed in the latter part of the paper.Expert opinion:While there are currently limited treatment options for dry AMD, more data are needed before we can truly evaluate the benefits of adopting risuteganib into the clinic. Conversely, several effective treatment options exist for DME; hence, risuteganib must show that it can add to these results, especially in those with refractory disease, before retina specialists adopt risuteganib into their treatment regimens.
