Breakthrough therapies often start with a scientific discovery, but discovery alone is not enough. Before a new treatment can reach patients, it must go through years of clinical research, safety testing, regulatory review, manufacturing, patient recruitment and data analysis.
For Steve Pakola, M.D., guiding therapies through that process has been the focus of his career for more than 30 years.
A licensed physician with decades of experience in the biopharmaceutical industry, including more than 25 years as a Chief Medical Officer, Pakola has worked across nearly every part of drug development.
His experience includes preclinical research, clinical development, regulatory affairs, biometrics and medical affairs, with programs involving small molecules, biologics and gene therapies.
The science has changed significantly over the course of his career, but his focus remains on determining whether promising new therapies are safe and effective enough to become treatment options for patients.
Why Rare Disease Treatment Innovation Needs a Different Approach
Developing treatments for rare diseases comes with challenges that differ from those seen in more common conditions.
Patient populations are often small and spread across wide geographic areas. Recruiting enough participants for a clinical trial can be difficult, and every aspect of study design must balance scientific rigor with the realities facing patients and caregivers.
Since joining REGENXBIO in 2019, Pakola has worked on gene therapy programs including RGX-121 for MPS II and RGX-202, a gene therapy candidate for Duchenne muscular dystrophy.
Under his leadership, RGX-121 advanced from its Investigational New Drug (IND) application through pivotal clinical development and Biologics License Application (BLA) submission. He also guided RGX-202 from IND through Phase III pivotal development, overseeing clinical strategy, regulatory planning and operational execution.
Beyond those programs, Pakola directed the first human gene therapy clinical trial in Brazil, helping expand patient recruitment internationally. He also led the clinical due diligence supporting REGENXBIO’s global partnership with AbbVie, which included $370 million upfront and the potential for up to $1.38 billion in milestone payments.
Despite the scale of those efforts, he says successful clinical development starts with understanding the people the therapy is intended to help.
“The most effective strategy is to design trials around the patient,” Pakola said.
That can affect everything from site selection to the number of visits a patient has to make. The goal is to make participation as easy as possible by cutting down on unnecessary travel, limiting extra visits and reducing the burden on patients and caregivers.
This is especially important in rare disease studies, where families may have to travel far for care, work with different specialists and stay involved in a study for years.
Pakola also believes patient advocacy groups should be involved early in the trial planning process. These groups can help researchers understand what daily life is really like for people with a rare disease, what matters most to patients and families and how to design studies that people can realistically take part in.
“Retention is often a function of trust and communication,” he said. “Patients need to feel informed, respected, and connected to the purpose of the study. When they do, engagement is much stronger.”
Clinical Trial Leadership: Turning Science Into Evidence
Clinical trials are where years of laboratory research are put to the test.
“Clinical trials are the engine of medical progress,” Pakola said. “They are the mechanism by which we translate scientific promise into evidence-based medicine.”
Every decision made during a clinical trial, from participant selection to data collection, helps researchers understand a therapy’s safety and effectiveness while providing the evidence needed for regulatory review and future treatment decisions.
Throughout his career, Pakola has led clinical programs across ophthalmology, cardiovascular disease, central nervous system disorders and rare genetic diseases. While each area presents different scientific questions, every study depends on collecting accurate, reliable information.
However, conducting those studies has become increasingly demanding.
Many now take place at research sites in several different countries, involve large amounts of data and require physicians, hospitals, sponsors and research organizations to stay aligned while regulatory requirements continue to change.
“One of the biggest challenges is complexity,” Pakola said. “Trials today are larger, more global, and more data-intensive than ever. That complexity can slow timelines and increase costs.”
Keeping a study on track takes careful planning, clear communication and strong teamwork. In many cases, the everyday decisions are just as important as the science behind the treatment.
Regulatory Strategy: Balancing Innovation, Compliance and Patient Safety
Gene therapies are changing what’s possible in medicine. Instead of managing symptoms, many are designed to address the underlying cause of disease, giving researchers and clinicians a different way to think about conditions with few effective therapies.
Developing those therapies means working in an area where the science is advancing quickly and the path forward isn’t always clear. Manufacturing, clinical trial design and evolving regulatory expectations all have to be considered alongside the science itself.
“Innovation and compliance should never be viewed as competing priorities,” Pakola said.
Planning for potential risks early, maintaining ongoing communication with regulators and anticipating manufacturing and trial design hurdles can help programs move forward more efficiently.
“At the end of the day, patient safety has to remain the anchor,” Pakola said. “If you maintain that principle, it creates a strong foundation for sustainable innovation.”
From Gene Therapy Researcher to Biotechnology Executive
Gene therapy has become one of the most closely watched areas of modern medicine, but Steve Pakola began working in the field well before it attracted widespread attention.
After earning his bachelor’s degree in biology and later his medical degree from the University of Pennsylvania, he conducted retinal gene therapy research at the university’s F.M. Kirby Center for Gene Therapy.
Working in the laboratory of Dr. Jean Bennett, he studied adeno-associated virus vectors and contributed to preclinical research supporting early translational development in ocular gene therapy.
“I was drawn to biotech because it sits at the intersection of science, medicine, and innovation,” Pakola said.
As his career progressed, Pakola moved from laboratory research and clinical medicine to leadership roles across the biotechnology industry.
He held early clinical development positions at Quintiles, Organon and Boehringer Ingelheim, where he worked on programs involving cardiovascular medicine, neuroscience and anticoagulation therapies.
Later, he served as Chief Medical Officer at ThromboGenics, where he helped lead the development of ocriplasmin, later marketed as Jetrea®.
As lead inventor and program leader, he guided the therapy through clinical development, regulatory review in the United States and Europe, and eventual approval as the first treatment for vitreomacular adhesion, including macular hole.
He continued to build leadership experience at Amakem and Aerpio Therapeutics before joining REGENXBIO.
The Power of Collaboration and Trust
Drug development depends on scientific expertise, but Pakola sees collaboration as just as important to a program’s success.
Modern development programs involve many different groups, including physicians, scientists, statisticians, clinical operations teams, manufacturing experts, regulators, investigators, patient advocacy organizations and patients themselves. Each one brings knowledge that the others may not have.
“I learned early in my career to reach out early and often to colleagues who know more than I do about so many parts of drug development,” Pakola said.
He also credits patient advocacy organizations and clinical research coordinators with playing important roles in successful studies. While they often work behind the scenes, they help connect researchers with patients, support trial participation and keep studies running smoothly.
Still, collaboration ultimately begins with trust.
“If there isn’t trust within the team, you’re sunk,” Pakola said.
As clinical trials become larger and involve more organizations around the world, he believes trust is what will allow teams to communicate openly, solve problems quickly and stay focused on the shared goal of improving patient care.
“The world doesn’t need more geniuses,” he explained. “It needs more people who work together.”
The Future of Clinical Development
Biotechnology continues to change quickly, with gene therapies, cell therapies and more personalized approaches creating new possibilities for treating disease.
Steve Pakola sees artificial intelligence becoming an increasingly important tool in that progress, supporting areas such as drug discovery, clinical trial design, data analysis and other parts of the development process.
“AI can’t work on its own,” he said. “It needs experienced experts to assess AI outputs, interpret them and make adjustments that lead to success.”
Looking ahead, Pakola sees medicine moving toward treatments that are more precise and tailored to individual patients.
“I believe we’re entering an era where therapies will become increasingly precise, targeted and potentially transformative—whether through gene therapy, cell therapy or highly personalized medicines,” he said.
Taken together, Pakola’s career and perspective point to a future of biotechnology shaped by scientific innovation, careful decisions and a continued focus on patients with diseases that have long lacked effective treatment options.
