Scaling Gene Therapy Clinical Trials Through The Lens Of Ophthalmology
By Huma Qamar, MD, MPH, CMI, chief medical officer, Ocugen
The promise of gene therapy has revolutionized the approach to treating rare diseases, offering hope for patients with conditions that previously had few or no treatment options. However, alongside the excitement comes the challenge of scaling these complex trials. Successfully expanding gene therapy trials requires not only a deep understanding of the science but also careful logistical planning, collaboration with specialized centers, and the foresight to manage future manufacturing needs.
The following insights in scaling gene therapy trials for rare diseases can provide a road map for navigating these challenges effectively.
The Complexity Of Gene Therapy Trials
Gene therapy trials, particularly for rare diseases, present unique complexities that traditional drug trials often do not face. One significant challenge is patient heterogeneity — there can be multiple mutations within a single disease category, and patients often have different disease progressions. This variability can affect patient responses to therapy, complicating safety assessments, especially in early-stage trials where dosing toxicity is a concern.
Beyond heterogeneity, the pathogenicity of the disease and differences in surgical techniques for various indications add to the challenges of treating these patients. For instance, understanding the role of medications prescribed before and after surgery to mitigate side effects such as ocular inflammation is crucial, as it is one of the most critical risks to manage. A conservative dosing strategy is essential to establish the right dose in humans while minimizing potential toxicity, particularly because gene therapy is irreversible. Early-phase trials are vital for ensuring safety and preventing adverse reactions.
The Role Of Specialized Surgeons And Centers
The expertise of surgeons and the type of clinical centers involved in gene therapy trials play a significant role in their success. Unlike more mainstream clinical procedures, gene therapy often involves surgical techniques. For instance, intravitreal injections are relatively straightforward, while subretinal injections require a higher level of expertise and are often performed under anesthesia. Surgeon skill levels can vary widely, with some performing dozens of simple injections daily and others conducting full surgeries.
Continuous education and standardization are critical components of trial success. The safety team oversees each dosing, with a representative present on-site to ensure adherence to protocols. This oversight is key to maintaining both safety and efficacy throughout the trial process. Developing a standardized surgical manual and ensuring adherence across multiple centers are fundamental to aligning surgical procedures with the drug’s mechanism of action.
Geographic And Site Selection For Trials
Choosing the right clinical sites is another crucial factor in scaling gene therapy trials. This includes prioritizing locations that are accessible to a considerable proportion of the patient population and provide adequate infrastructure. Sites must also be staffed with a capable workforce that can appropriately recruit patients who meet inclusion and exclusion criteria, are willing to travel, and are prepared for subretinal injections, which have long-term implications compared to intravitreal procedures that typically require repeat treatments over months.
Clinical trial sites must be research hospitals or specialized centers that can handle the complexities of gene therapy trials; they cannot be typical outpatient clinics. Investigators ideally have five to seven years of experience and prior participation in similar gene therapy trials. The proper combination of logistics, specialized equipment, and skilled personnel ensures that the trials proceed smoothly.
Managing Logistical And Manufacturing Challenges
Scaling gene therapy trials requires overcoming substantial logistical and manufacturing challenges. The supply chain for gene therapy products must be managed carefully due to their short shelf life and the need for continuous patient monitoring. Subretinal gene therapies, fortunately, offer an extended shelf life and a longer-lasting effect compared to intravitreal gene therapies, easing some of the logistical pressures.
Ensuring quality and reliability hinges on selecting the right partners. Forming strategic partnerships allows for dependable delivery of materials and services, mitigating the risk of costly delays. Processes and partnerships that enhance scalability are vital as therapies move toward commercialization.
Ensuring Quality and Consistency in Patient Care
Maintaining consistent patient care across various centers poses another challenge. Standardized internal data controls, detailed study manuals, and a centralized data repository help uphold these standards. Proper masking and study control systems are also employed, alongside regular data and safety monitoring. The independent Data and Safety Monitoring Board (DSMB) plays a crucial role by reviewing patient data periodically to maintain transparency and ensure patient safety throughout the ongoing clinical trials.
Turning Challenges Into Milestones
Scaling gene therapy clinical trials is no small feat. It demands a blend of scientific insight, logistical strategy, and robust partnerships. Success lies in thinking beyond conventional boundaries — through patient care, surgeon training, and site selection. As these therapies continue to progress and move toward broader application, the lessons learned from these trials will be crucial in delivering transformative treatments to patients worldwide.
About the Author:
Huma Qamar, MD, MPH, CMI, is the chief medical officer for Ocugen, a biotechnology company focused on discovering, developing, and commercializing novel gene and cell therapies and vaccines. In her role, she oversees clinical development and medical operations, including vaccine trials and mid-to-late-stage clinical trials for Ocugen’s novel modifier gene therapy platform, which has the potential to treat multiple retinal diseases. Dr. Qamar has extensive experience in clinical research, having worked at institutions such as Yale, Harvard, and the University of Pennsylvania. She previously authored “A Vision For Inclusion: Designing Trials That Benefit Visually Impaired Patients.”