Gene therapeutics offer hope to many people with genetic and degenerative diseases. This includes those suffering from a muscle wasting disease. The underlying technology, however, is highly novel as only a few gene therapeutics are just now entering the market. This naturally raises many questions, some of which are answered below.
You can also learn more about gene therapy and muscle wasting diseases like the inflammatory myopathies, muscular dystrophies and cancer cachexia by visiting the links at the bottom of the page.
Is gene therapy safe?
AAV-based gene therapeutics have proven safe and well-tolerated in almost every clinical trial conducted to date. Although mild adverse events have been noted in some trials and serious events with high doses of AAV9 or AAV8 serotype vectors, the latter are rare. Note that AAVogen uses an AAV6 serotype vector with an excellent safety profile. This is why the current resurgence in gene therapy is often described as the "golden age" for this technology.
No drug is absolutely safe, however, which is why particular care is taken when conducting clinical trials with emerging technologies like gene therapeutics. It's important to understand that despite the name, the adeno-associated viral vectors used today are entirely unrelated to the adenoviral vectors that produced tragic consequences in the '90s.
Is AAVogen conducting clinical trials with AVGN7?
We are currently conducting safety/toxicology studies. We are also expanding our proof-of-concept studies to include different disease indications. Detailed clinical trials are of coursed planned and will start in the near future.
What are the prioritized indications for AVGN7?
Excellent question! Because AVGN7 antagonizes the fundamental biochemical events that are activated in many if not most muscle wasting disease states, it could potentially be used to treat a wide variety these disease indications.
Nevertheless, a focused development plan is key to quick market entry for any drug and to optimize its clinical impact. We have, therefore, parsed our development program to prioritize inclusion body myositis (IBM) as the lead indication in the short-term while we continue to develop the Duchenne muscular dystrophy (DMD) and peripheral neuropathy programs.
Targeting an orphan disease like IBM ensures rapid market entry. It also provides the additional time needed to develop a combinatorial approach for treating DMD or to develop into a large market disease indication like peripheral neuropathy.
How serious is IBM, is it fatal?
IBM is a very serious and debilitating disease. It is often misunderstood as not being fatal when recent studies clearly demonstrate that IBM contributes to premature mortality. Quality of life also substantially declines as subjects lose mobility as well as the ability to perform even basic tasks of life. It's important to understand that gene therapeutics have been developed for non-fatal disease indications including night blindness and this establishes a regulatory precedent for applying this technology in treating other indications that may or may not be considered fatal.
Note that IBM and the other inflammatory myopathies, all of which are potential disease indication candidates, cannot be treated with a monogenic gene therapy for one very simple reason; they aren't caused by genetic mutations. Successful therapies must overcome the inflammatory signals that cause muscle wasting, restore muscle mass and be durable. Animal studies suggest that AVGN7 can accomplish all of these goals, which fuels our optimism.
Why combinatorial therapy for DMD?
There is little doubt that replacement gene therapy works. Many studies have proven the utility of adding a functioning gene into a cell, tissue or animal that harbors a genetic mutation. This is why big pharma has embraced the gene therapy approach especially for treating the muscular dystrophies.
However, and this is extremely important, no study has ever completely restored dystrophic muscle to normal. In fact, most studies with dystrophic animals used young animals that express a mild phenotype unlike that in human patients. The few studies using older animals or those that exacerbate the phenotype with exercise - a method that mimics injury-induced muscle degeneration in patients - report only partial restoration of muscle function.
All of this suggests that additional measures to boost muscle mass and strength are needed to overcome the accumulated damage from years of muscle degeneration. This is why we are developing a combinatorial approach, one that pairs AVGN7 with gene replacement or correcting therapeutics.
What are AAVogen's investment and development needs?
AAVogen is supported by grants and seed investments and is currently raising additional financing. These funds will support our pre-clinical development program and Phase I clinical trials.
Our financing goals are tranched to particular milestones and are leveraged by a record of highly successful grantsmanship, strong intellectual property protection, equally strong legal representation and experienced management/leadership. We are also pursuing corporate partnerships and licensing to expand value propositions in all geographies.
For more information about investing or partnering with AAVogen, please visit the Investing page.