Regenxbio’s wet AMD gene therapy shows promise in phase 1

Regenxbio reported promising interim data from a phase 1 trial of its gene therapy for wet age-related macular degeneration (AMD). The treatment, designed to combat vision loss caused by the formation of new blood vessels in the eye, reduced the need for in-eye injections of anti-VEGF drugs. The company is now looking to move the treatment into phase 2. 

Considered incurable, AMD is treated with intraocular injections of drugs—such as Regeneron’s Eylea and Roche’s Avastin and Lucentis—that target VEGF (vascular endothelial growth factor), a protein that stimulates the growth of blood vessels. These drugs prevent the growth of leaky blood vessels in the eye that cause wet AMD's signature scarring, death of photoreceptors and ultimately, vision loss. While these injections are the most effective treatment for wet AMD, getting regular injections into the eye can be unattractive for patients. 

A one-time gene therapy would address this concern. Regenxbio’s RGX-314 uses an adeno-associated virus to deliver a gene that encodes a protein that neutralizes VEGF activity. The phase 1 study divided 18 patients into three groups that received three different doses of the gene therapy. The patients must have had a history of frequent anti-VEGF treatment, as well as a history of responding to these treatments, to qualify for the trial. 

The study found the gene therapy to be safe and well-tolerated at all doses. All three groups had dose-dependent protein expression levels and dose-dependent reduction in anti-VEGF injections. The mean protein levels measured increased dramatically as the doses increased: the group receiving the lowest dose had a mean protein level of 2.4 ng/ml, while the higher doses posted levels of 12.8 and 160.2 ng/ml. Three patients in the group that received the highest dose did not need anti-VEGF injections in the six months after treatment. When compared to the six months prior to their most recent anti-VEGF injection, the injection rate for this group after gene therapy was reduced by 53%. 

"We are very encouraged by the positive interim data for RGX-314 and the potential of NAV gene therapy as a one-time treatment for wet AMD, particularly as this is a nonrare patient population with a significant treatment burden," said Kenneth Mills, Regenxbio’s president and CEO, in a release. "Regenxbio looks forward to applying what we are learning from this trial to expand the RGX-314 clinical program into a phase 2 trial and bring this novel therapy to patients as quickly as possible."  

Regenxbio will move the highest dose, 6 x 1010 genome copies (GC) per eye, into phase 2 and will introduce an even higher dose, 1.6 x 1011 GC per eye, into the phase 1 trial. It plans to start the phase 2 study in 2019. 

Despite the early promise of its wet AMD program, Regenxbio's shares dipped Tuesday morning as the company reported some safety issues in a trial testing its gene therapy for homozygous familial hypercholesterolemia. Two patients had elevated levels of liver enzymes called transminases and one of them had to be hospitalized.