Gene Therapy for Rare Diseases: Considerations in Translational PK/PD and Clinical Pharmacology

Session Description

The gene therapy modality is a therapeutic strategy that provides genetic modification DNA to a patient’s cells to correct a defective gene or a gene product in order to treat diseases. Gene therapy techniques can include replacing or inactivating a mutated gene or introducing a new gene into the body. Recently approved gene therapy modalities include the first oligonucleotide-based therapies (Spinraza, Exondys 51, Vyondys 53), three cell therapies (Kymriah, Yescarta, Tescartus), and two in vivo AAV gene therapies (Luxturna and Zolgensma).

The exciting and rapidly developing field of gene therapy (GT) poses unique challenges for the traditional clinical pharmacologists in facilitating the timely development of new treatments that are both safe and efficacious. Clinical development programs for gene therapies differ in some important respects from those used for small molecule drugs. Clinical pharmacologists are now faced with the traditional set of questions that requires non-traditional answers and approaches. For example, while translational Pharmacokinetic / Pharmacodynamic (PK/PD) modeling is routinely conducted for traditional therapeutic modalities to project clinical dose and response, it is still a relatively nascent area for GT. In addition, many of these GT target rare genetic diseases with significant unmet need. This represents additional challenges that are inherent to rare diseases, such as recruitment challenges, heterogeneity of the disease, uncertainties in endpoints, and biomarker selections, etc. Given these challenges, the translational aspects of GT become extremely important as the first-in-human trial may end up being the registration trial. Regulators are often left with some levels of uncertainty, despite granting approval.

This session highlights the current efforts that are undertaken by regulators and drug developers to help address some of these unique questions and challenges. The crucial issues related to translational PK/PD aspects of GT are presented, and methodologies, such as dose scaling and semi-mechanistic modeling, are discussed in detail. Finally, immune response, durability, and variability are highlighted as areas where deeper mechanistic understanding would greatly benefit the quantitative approaches to gene therapy development.

Learning Objectives

1. Introduce gene therapy modalities and discuss the impact of GT from a clinician’s and regulator's perspectives with respect to efficacy, safety, and patient challenges related to the new modalities, especially for rare diseases.

2. Understand, through case studies, the role of the clinical pharmacologist and quantitative pharmacology in development of gene therapy, as well as how to overcome some of the challenges.

Session Schedule

3:00 PM - 3:04 PM ET
Opening Remarks
Mariam Ahmed, PhD and Gina Patel, PhD

3:04 PM - 3:15 PM ET
Gene Therapy: Landscape and Regulatory intelligence
Noha Rayad, PhD

3:15 PM - 3:25 PM ET
Clinical Pharmacology Aspects of Gene Therapy Development for Rare Diseases
Kefeng Sun, PhD

3:25 PM - 3:36 PM ET
Deployment of Quantitative Modeling Approaches to Gene Therapy Development
Piet van Der Graff, PharmD, PhD

3:36 - 3:43 PM ET
Until My Son Calls Me “Dad”: Re-inventing the Drug Development Industry for One Person
Sanath Kumar Ramesh

3:43 PM - 4:00 PM ET
Live Q&A and Closing Remarks
All Speakers