Led by a USC cell and gene therapy researcher, an international coalition calls for more transparency and reproducibility in research and development of breakthrough treatments.
By Jeremy Deutchman
Scientists around the world are achieving significant advances in the fight against devastating diseases like cancer, severe combined immunodeficiency (SCID) disorder and amyotrophic lateral sclerosis (ALS) thanks to leading-edge cell- and gene-based therapies. But numerous obstacles to progress could slow down those advances including insufficient evidence of effectiveness and market-driven economic uncertainties.
An editorial just published in Molecular Therapy Methods and Clinical Development — a journal of the American Society of Gene and Cell Therapy — seeks to address these issues. Mohamed Abou-el-Enein, MD, PhD, executive director of the joint USC/Children’s Hospital of Los Angeles Cell Therapy Program and associate professor of clinical medicine, pediatrics and stem cell biology and regenerative medicine at the Keck School of Medicine of USC, has gathered a group of more than 30 high-profile individuals and institutions to recommend improvements in the development of cell- and gene-based therapies. In a call to action, the signatories make a case for better evidence generation and research reproducibility in clinical and pre-clinical studies they say are overdue. Molecular Therapy Methods and Clinical Development plans to devote a special issue to the topic as well.
“The field of cell and gene therapy has unprecedented potential in treating diseases that were previously untreatable, but the unique characteristics of these individualized treatments has changed the paradigm of drug development and regulatory evaluations,” Abou-el-Enein says. “These products are now progressing to market with less data than the regulatory standards mandate to ensure their safety and demonstrate their clinical benefits. As much as we need these life-saving therapies, we must do more to guarantee they have sufficient evidence on their safety and efficacy to survive in a competitive pharmaceutical market.”
Among the signers of the op-ed are the presidents of the US National Academy of Medicine, and the American Association for the Advancement of Science (AAAS), the director of the European Medicines Agency, director of the Center for Biologics Evaluation and Research within the Food and Drug Administration, and heads of universities and organizations ranging from Harvard Medical School to Fred Hutchinson Cancer Research Center. They propose an emphasis on consistent and high-quality evidence that can justify regulatory licensing and health insurance coverage and reimbursement.
“We are seeing signals in the field we cannot ignore, and we need to start galvanizing the scientific and regulatory communities,” Abou-el-Enein says. “Already, we have witnessed the withdrawal of five cell- and gene-based therapies from the EU market because the limited data available could not justify the high cost of treatment. We want to avoid a repeat of this situation, and that can only happen with more robust, and better designed, clinical development programs.”
Gene therapies often rely on introducing permanent changes to human cells and tissues, which can increase the risk of unforeseen and delayed adverse events. Combined with the high unmet medical needs for these products and numerous other factors (such as heterogeneity in treatment response and toxicity; targeting rare diseases with low patient accrual; and the need for customization, which impedes the creation of “off the shelf” products), the therapies can get approved prematurely, triggering unexpected consequences that can lead to setbacks for the field.
“This group hopes to nurture the development of long-term follow-up data and real-world evidence while encouraging the publication of not only positive but also meaningful negative experimental results,” Abou-el-Enein says. “It’s the surest way to sustainable innovations with the power to save patients’ lives.”