FDA grants Fast Track Designation to NGM Bio’s NGM621

NGM Biopharmaceuticals Inc. announced that the FDA has granted Fast Track designation to NGM621, a monoclonal antibody product candidate engineered to potently inhibit complement C3, for the treatment of patients with geographic atrophy (GA) secondary to age-related macular degeneration.

NGM Bio is currently evaluating NGM621 in its ongoing Phase 2 CATALINA study and a topline data readout is expected in the fourth quarter of 2022.

“The FDA’s decision to grant Fast Track designation to NGM621 is an important milestone underscoring the high unmet medical need for patients with geographic atrophy as well as the potential of NGM621 to alter the course of this disease for those underserved patients,” Erin Henry PhD, head of Ophthalmology at NGM Bio, said in a statement. “Patients living with geographic atrophy lose approximately one line of vision on the eye chart each year, impacting their ability to do everyday tasks such as driving and reading and reducing their independence and quality of life. We are committed to improving outcomes for these patients and this designation, with its potential for more frequent interactions with the FDA, may help accelerate our efforts to do so.”

The Fast Track process was designed by the FDA to facilitate the development and expedite the review of potential therapeutics intended to treat serious conditions and address unmet medical needs. Fast Track-designated programs are given the opportunity to engage in early and frequent communication with the FDA throughout the entire development and review process and may be eligible for prioritized review and accelerated approval if relevant criteria are met.

About Geographic Atrophy

GA is an advanced form of age-related macular degeneration characterized by progressive retinal cell loss that results in irreversible loss of vision. The disease affects approximately one million patients in the U.S. and five million patients globally. There are currently no treatments for GA approved by the FDA or the European Medicines Agency.

About NGM621 and Complement C3 Inhibition

According to the company, NGM621 is a proprietary humanized Immunoglobulin 1 monoclonal antibody product candidate engineered to potently bind to, and be a long-acting inhibitor of, complement C3 activity. The therapeutic is delivered via intravitreal (IVT) injection and is being evaluated with dosing intervals of every four and eight weeks. NGM621 Phase 1 study results [NCT04014777] showed single and multiple IVT injections appeared to be safe and well tolerated. In preclinical models, NGM621’s high affinity binding to C3 has demonstrated the potential for potent C3 inhibition, and NGM Bio’s pharmacokinetics/pharmacodynamics modeling has shown sufficient drug coverage for potential every-eight-week dosing.

The company noted that its preclinical data also suggest that NGM621, unlike PEGylated molecules, may not exacerbate choroidal neovascularization (CNV); the human translation of this observation is being investigated in the fully enrolled, ongoing Phase 2 CATALINA clinical trial [NCT04465955].

C3 is a key component of the complement system, which helps orchestrate the body’s response to infection and maintains tissue homeostasis. The complement cascade can be activated through its three distinct pathways – classical, lectin and alternative – all of which converge to activate C3. When this cascade is dysregulated, the immune response may lead to the development and progression of GA. Inhibition of C3 represents a promising therapeutic approach that broadly inhibits downstream effector functions triggered by the excessive activation of the complement pathway, including inflammation, activation of the adaptive immune system, opsonization (the marking of a pathogen to be destroyed by phagocytes, a type of immune cell), phagocytosis and cell lysis (cell death).

NGM621 was discovered by NGM Bio under its strategic collaboration with Merck, known as MSD outside the United States and Canada.

NGM621 Phase 2 CATALINA Study

According to the company, the Phase 2 CATALINA study enrolled 320 patients diagnosed with GA in one or both eyes. The primary objectives of this multicenter, randomized, double-masked, sham-controlled study are to evaluate the efficacy and safety of NGM621 when given every four weeks or every eight weeks via IVT injections compared to sham control. Patients are randomized to one of four treatment groups in a ratio of 2:1:2:1 to receive IVT injections of NGM621 or sham every four weeks or every eight weeks for a total of 52 weeks and monitored for an additional four weeks upon treatment completion for a total of 56 weeks.

The primary efficacy endpoint is the rate of change in GA lesion area, as measured by fundus autofluorescence (FAF) imaging, over 52 weeks of treatment. The primary safety endpoints will evaluate the incidence and severity of ocular and systemic adverse events from treatment with NGM621 compared to sham control.