Virtual ASCPT 2022 Annual Meeting

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.

Early-stage drug development and pre-approval trials typically exclude pregnant/lactating mothers, and children until late in drug development, or at times, until years after approval. Given this limitation, the evidence on drug safety, efficacy, and optimal use in these special populations much-needed to inform drug labeling is lacking. As a result, this encumbers heavy reliance on the data obtained during trials and data from post-approval controlled observational studies for drug labeling and dose optimization. In the era of model-informed drug development, much emphasis is laid on incorporating data obtained during the clinical trial, i.e. real-world data (RWD), to generate real-world evidence (RWE). This is increasingly utilized to monitor post-market safety, adverse events, and regulatory decision-making. RWD is data relating to patient health status and/or the delivery of health care routinely collected from different sources. Sources of RWD include electronic health records, claims and billing data, product- and disease-based registries, and data from mobile and wearable devices, etc. Incorporating the collection of RWD from thoughtful study designs serves as an efficient tool for assessment of drug-associated safety issues in pregnant/nursing mothers. Regulatory agencies are increasingly recommending complementing pregnancy registries with pregnancy cohorts nested within healthcare utilization databases for assessment of drug safety/optimal use. Furthermore, in-silico modeling strategies (PBPK modeling) utilizing RWD can be incorporated for dosing optimization in pregnant women, for which current dosing approaches are rather empirical. In addition, the pediatric population presents specific challenges to drug safety assessment, such as long-term follow-up, is needed to observe effects over multiple developmental stages that can be cumbersome with post-approval observational studies. Besides, children take medications less often than adults, and measurement of rare events requires large databases. To address these challenges, RWD can be utilized to inform our understanding of both prenatal as well long-term effects of drug exposure early in children’s development.

Join ASCPT for a friendly game of trivia while networking with colleagues! This session will be hosted by ASCPT Early Career Community Past Chair Songmao (Ben) Zheng, PhD. Trivia questions will be science and non-science based. Participants will compete for fun, glory, and a prize! Please plan on joining on a device that supports Zoom and have a mobile device ready to play the game!

The elderly population is projected to increase to 88 million in the US by 2050 and to exceed the number of children by 2040 globally. In 2018, the US population of the 75-84 year group (15.4 million) was 20 times larger than in 1900. 85 and older elderly are predicted to be more than double from 2008 to 2040 (6.5 million to 14.4 million). Older people are considered a “special population” because they are more vulnerable to adverse drug effects than younger adults, potentially due to decreased organ function, comorbidity and polypharmacy. However, data on safety and efficacy of medication use in the elderly who are 75 years and older are sparse. They are generally excluded in clinical trials due to polypharmacy, complex pathophysiology and decreased organ function. Experts agree that drug dosing regimens used in younger adults are unlikely to adequately inform drug prescribing for the aging population, especially for those at the middle and oldest end of the age span. Collectively, a critical gap remains regarding the safety and effectiveness of medication use in this special population. This knowledge gap is particularly problematic because the new age elderly (≥75 years) might be prone to more severe manifestations of side effects due to comorbidities with polypharmacy. Additionally, current knowledge is focused on typical old adults, not those who are 75 years and older. Several questions are unclear such as how do comorbidities impact on drug’s disposition; are there pharmacokinetic difference between youngest-old, middle-old, and oldest-old patients; what is the effect of age on the expression and activities of phase II enzymes and transporters. This innovative interactive session will define problems and gaps and provide potential strategies to address those challenges in the new era, which can foster research in the community to provide the right dosing to this special population.

The ability to informatively and succinctly communicate one’s science is a critical skill that trainees must learn to be successful professionals within the pharmacology field. While formal coursework to develop communication skills may be lacking in graduate program curricula, professional society meetings can give trainees the opportunity to hone their scientific communication skills. As such, ASCPT is a key player in providing trainees experience in communicating their science to professionals of the field as well as provide opportunities to learn communication skills from these professionals. Therefore, this session merges communication education and trainee presentation skills in a friendly, interactive competition to highlight the value of excellent research communication and trainee member research.

Register now for the re-envisioned ASCPT Speed Mentoring session as registration is limited! ASCPT recognizes the importance of supporting the networking, growth, and development of those working in clinical pharmacology and translational science. Everyone can benefit from colleague-to-colleague learning opportunities, regardless of career level. ASCPT is offering this session multiple times during the Annual Meeting so there are opportunities convenient for attendees in all time zones! Register for this session during your Annual Meeting registration if you would like to engage with like-minded experts who can serve as a sounding board and offer their own tried and true experiences as a peer to develop your personal and professional career goals. This event is an enriching opportunity for 1:1 consultation with other participants in academia both with and without clinical experience, regulatory, and industry. There are no conditions to participating but the experiences are sure to be rewarding!