Journal Impact Factors: What do the Numbers Mean?
The use of anti-VEGF therapy has revolutionized the treatment of wet AMD, such that most patients can now maintain functional vision for their lifetimes. However, the need for frequent injections results in a tremendous burden on the patient, the provider, and the healthcare system. The first investigational effort to extend the duration between injections through an implantable port delivery system has been completed. Carl Awh, MD recently presented the Phase 2 LADDER (Genentech, a member of the Roche group) results at the 36th Annual Meeting of the American Society of Retina Specialists (ASRS) in Vancouver, Canada. We caught up with Dr. Awh to highlight the top line results.
What is the LADDER study design?
LADDER is a Phase 2, randomized, active treatment controlled, dose-ranging trial of the Port Delivery System (PDS) with ranibizumab for nvAMD. LADDER compared monthly intravitreal injections of ranibizumab with the PDS using 3 different ranibizumab concentrations: 10 mg/ml, 40 mg/ml, and 100 mg/ml.
The PDS is surgically implanted at the pars plana and is covered by conjunctiva and tenon’s capsule. Refill are performed in the office.
What was the primary endpoint?
The primary endpoint was the time to the first required refill of the PDS.
There was a dose-response observed among the 3 treatment arms. The median time to first refill in the 10 mg/ml arm was 8.7 months; in the 40 mg/ml arm, 13.0 months; and, in the 100 mg/ml arm, 15 months.
In eyes that lasted 6 months or more, were both functional and anatomical improvements similar to monthly anti-VEGF injections?
Yes. 80% of eyes in the 100 mg/ml arm went at least 6 months without receiving a refill. At 9 months, the visual acuity and anatomical (OCT) response was comparable to that achieved with monthly injections. These outcomes were maintained through month 18 for available patients (not all patients have yet reached the 18 month follow-up time. When this data was captured, the average time on study was 16.8 months for patients in the 3 PDS arms.)
What were the outcomes of eyes that required rescue? Were they similar to monthly injections at the end of the study period?
Overall outcomes, which included eyes that needed refills, were comparable to those achieved with monthly injections. The sub analysis of only eyes that required refills is not yet available, but that information will be made available.
Were there any surgical complications?
Yes. Vitreous hemorrhage was the most common initial complication, but a modification of the surgical technique, in which a laser probe is used to coagulate the choroid prior to choroidotomy, reduced the incidence of vitreous hemorrhage to around 5%, most of which were mild.
Were there other complications?
Other complications consistent with a new vitreoretinal surgical technique included retinal detachment and endophthalmitis, but the numbers were within the range predefined as acceptable at the outset of the trial.
The PDS Phase III clinical development program is expected to begin later in 2018