Advancements in Gene Editing Therapies Pose New Challenges

The biopharmaceutical industry is currently at a crossroads that will propel research into an entirely new paradigm with the introduction of gene editing therapies that could lead to cures. Dr. Tshaka Cunningham, Associate Director of Scientific Collaboration for DIA, will discuss his perspectives on advancements in gene editing therapies and their impact on the industry. Before joining DIA, he served as the Scientific Program Manager for the Aging and Neurodegenerative Diseases Rehabilitation Research Program at the U.S. Department of Veterans Affairs within the Veterans Health Administration’s Office of Research & Development (VHA ORD). He previously worked as a research scientist at Bristol-Myers Squibb Pharmaceuticals Inc., where he developed biological screening assays to identify drugs for the treatment of cardiovascular diseases. Dr. Cunningham has expertise in various topics including the latest on CRISPR gene editing, gene therapy/genomics, and the importance of bridging the gap between scientific observation and actual clinical outcomes.

Moe Alsumidaie: What types of trends do you anticipate expecting precision medicine in the coming years?

Tshaka Cunningham

Tshaka Cunningham: I think it's an exciting time for advanced therapies, which are typically based on individual genetics that are very personalized, and I believe we are going to see some level of combination between traditional pharmaceuticals and genetic-based therapies in the not-too-distant future. This area of science is new, and people forget that gene editing was only pushed out on the scientific scene maybe six to seven years ago. The rapid rate at which the technology has developed to now with the first clinical trial being undertaken by some therapeutics enterprises for gene editing, is very exciting. I suspect regulations are going to get a lot better, and a lot more precise as the field develops, and I think the ability to combine the traditional pharmacological intervention with novel gene-based therapeutics will be very interesting; for example, to use gene therapy to set a tumor cell up to be more responsive to a given chemotherapy. I suspect the first therapeutic indications that will be impacted by this technology are monogenetic diseases, such as cystic fibrosis sickle cell, and Huntington's disease.

MA: What current regulatory hurdles exist with running clinical trials in using this particular technology? 

TC: I can't speak for the FDA or regulatory agencies. I'm only speaking from my perspective as an observer of the whole field. I think that the technologies are still very new, particularly, gene editing. Based on discussions with regulators, patient advocates, and company executives at DIA, there is much talk about how to advance precision medicine, gene therapy, and gene editing. What was concluded is that there's a need to move carefully with this new technology to make sure no harm is done (i.e., inducing mutation, or something that you don't want to have), but, you also want to move very deliberately because there are patients suffering from diseases who really need those therapies. So, regulatory agencies have to balance those priorities to protect the patient, but also make sure there are opportunities for therapeutic advancement. I think the FDA and other regulatory agencies are going to understand the science and help companies and entities that are seeking to develop these therapies by helping them navigate some of those regulatory questions (i.e., safety, target ratio, efficacy, andtolerability). I think just like with any drug; we're going to go through that process but, because it's a genetic drug, it'll be more sophisticated.

MA: What challenges are involved with developing these novel therapies?

TC: The biggest challenge involves pushing through innovation, and like any breakthrough initiative, companies are going to face numerous challenges. For example, gene therapy had some early excitement, which led to a big controversy with one trial that went awry and a patient died; that event set the field back, but, over time, the field continued to advance new therapies and with some now FDA approved (i.e., immunotherapies). We may have experienced that with gene editing as well; the technology is new, and we’ve seen the FDA put a clinical hold on all U.S. based studies for a company running gene editing studies, and they're asking for more information. That's appropriate because we need to understand the drug’s safety profile before continuing human trials. Once these safety questions have been answered to the satisfaction of regulators, then these therapies should able to move forward in the development process just as traditional pharmaceuticals. 

MA: Will the introduction of these novel therapeutics reduce the cost of treatment for patients?TC: There is a possibility of that; The pricing will likely be much different fromtraditional pricing for chronic treatments, because in some cases these therapies may be curative. For example, the Hepatitis C drug (Solvaldi) had a very high price tag compared to other traditional pharmaceuticals. However, when comparing the drug to the lifetime cost for a patient (i.e., getting a liver transplant), the cost is three to four hundred thousand dollars versus eighty to a hundred thousand. So, the cost benefits are there. For other diseases, particularly severe life-threatening diseases like cancer (for which the treatment prices are very high), a half-million dollar price tag might be acceptable for those therapeutics. The pricing is going to be very interesting for these diseases, particularly the ones that are curable because once a cure is found, those companies will also face pressure because they will be eliminating the market. 

MA: How is DIA helping to advance this innovation?TC: What we have to do at DIA is support advancement in this field by bringing academics, industry professionals, as well as regulators and patient advocates to our meetings and supporting a neutral forum to discuss varying perspectives, just like we did at our annual meeting and our breakout session on precision medicine, gene therapy, and gene editing. We're at a point in our history at DIA where our ability to communicate, particularly internationally and instantaneously is higher than it's ever been. DIA is a great example of an organization that convenes thought leadership to help drive the field forward to help stimulate innovation and progress in a given field, and this will most certainly be the case for the field of advance therapies including precision medicine, gene therapy, and gene editing.

Moe Alsumidaie, MBA, MSF is Chief Data Scientist at Annex Clinical, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials.