The Developing Regorafenib Eye drops for neovascular Age‐related Macular degeneration (DREAM) study: an open‐label phase II trial

Abstract

Aims This programme investigated topical regorafenib, a multikinase inhibitor, in patients with neovascular age‐related macular degeneration (nAMD). Methods Topical regorafenib was investigated in an open‐label, phase IIa/b study in which patients with choroidal neovascularization (CNV) secondary to nAMD received regorafenib (25 μl, 30 mg ml–1) three times a day for 12 weeks. The primary endpoint of the phase II/a/b study was mean change in best‐corrected visual acuity (BCVA) from baseline to weeks 4 and 12. Results In nAMD patients (N = 51), mean changes in BCVA were +1.2 [90% confidence interval (CI) –0.61, 2.97] and −2.4 (90% CI −4.18, −0.54) letters at weeks 4 and 12, respectively. Ocular treatment‐emergent adverse events (TEAEs) (study eye) were reported in 21 patients by week 12. There was one serious ocular TEAE (visual acuity reduced) that was not drug related. Twenty patients required rescue (intravitreal ranibizumab). Conclusions The programme was terminated after phase IIa ended because efficacy was lower than with current nAMD treatments. According to elaborate post hoc analyses, the most likely reason was insufficient exposure in the target compartment (back of the eye).

Evaluation of Long-Lasting Potential of Suprachoroidal Axitinib Suspension Via Ocular and Systemic Disposition in Rabbits

“…The limitations of current anti-VEGF-A therapies, such as treatment burden 10,11,[36][37][38][39] and ceiling effect, [40][41][42][43] in the management of nAMD has been highlighted by large real-world retrospective clinical studies. Topical delivery of several tyrosine kinase inhibitors, such as TG100801, 44 pazopanib, 45 regorafenib, 46 and acrizanib, 47 resulted in suboptimal clinical efficacy. More recently, IVT administered sustained release formulations of sunitinib and axitinib have shown preliminary efficacy and safety in phase I/IIa studies for the treatment of patients with nAMD.…”

Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives

“…Loftsson et al and Sigurdsson et al previously designed dexamethasone-cyclodextrin complexes for topical drug delivery to the posterior segments of the eye [ 141 , 142 ]. Recently, topical regorafenib, a multikinase inhibitor used to treat neovascular AMD, was investigated in an open-label phase 2 clinical trial (DREAM; NCT02222207) to determine its efficacy [ 143 ]. By week 12, 21 (41%) of the 51 subjects required intravitreal ranibizumab rescue due to ocular treatment-emergent adverse events.…”

New Drugs in the Pipeline for the Management of AMD

“…Although regorafenib, pazopanib, and LHA510 failed, other therapies showed promising results [52][53][54]. These formulations have the great advantage of being less invasive, but they can decrease the possibility of monitoring treatment compliance, as it happens with glaucoma patients medicated with lowering ocular hypertension drops.…”