The third in our series of insights from the 2023 WCG Clinical Research Trends and Insights report focuses on the outlook for oncology, cell and gene therapy, and central nervous system research.

The Emerging Use of Adjudication in Oncology for Determining Patient Eligibility

Shaena Kauffman, Executive Director, Operations EAC, WCG

One of the most interesting trends over the past year has been the increased use of endpoint adjudication committees (EAC) to determine patient eligibility, especially in oncology clinical trials. This trend will likely continue in 2023. Adjudication of inclusion criteria, or eligibility adjudication, has been used in clinical trials where inclusion criteria are subjective. The independent assessment by an EAC gives regulators and scientists confidence in the comparability of clinical trial subjects. Previously, this type of adjudication has been applied to areas such as progressive neurological disease or heart failure, where medical expertise is required or eligibility is subjective. However, there is a rising trend in using EACs to confirm oncology disease progression to demonstrate a consistent evaluation for patient eligibility and provide real-time feedback to the study sites.

In the area of disease progression, adjudication has the potential to mitigate variability and increase the strength of the clinical trial results. In addition to bolstering the clinical trial data against the regulatory and scientific rigors, EAC members can serve as a resource to study sites that may need access to experts to assess some of the more complex patient eligibility criteria. Of course, the most significant benefits are that adjudication of inclusion criteria reduces protocol deviations and enforces scientific rigor through a pre-randomization, standardized objective assessment. The use of eligibility EACs will continue to expand in 2023 as sponsors and sites report the benefits.

mRNA: Not Just for Vaccines

Daniel Kavanagh, PhD, Senior Scientific Advisor, Gene Therapy, WCG

Reflecting a new emphasis on cell and gene therapy (CGT) for 2023, the FDA recently announced a new “super office,” the Office of Therapeutic Products (OTP), to replace the former Office of Tissues and Advanced Therapies. Included in the announcement are plans to increase hiring and issue more CGT guidance documents in the coming year.

The year 2022 saw many new advances in CGT, including FDA approvals for new products and supplemental indications for genetically modified cellular therapies and vectored gene therapies. In 2023, one area to watch closely is that of “vectorless” mRNA therapeutics. Synthetic mRNA is a powerful tool that can program cells for new therapeutic functions. When combined with rapidly developing nanoparticle technologies, mRNA therapeutics may be targeted to a wide array of cell types and tissues. One potential application of gene transfer technology is to bypass the complex in vitro manufacturing process currently required for biologics and turn the body’s own cells into temporary factories to produce antibodies, enzymes or vaccine antigens. Many such approaches in development rely on mRNA.

Currently approved gene therapies tend to produce long-lasting or permanent changes in cellular programming and may induce immune responses that prevent re-dosing. For these reasons, many gene therapies are designed for “one-and-done” curative administration. This offers new hope to patients and their families, but also presents challenges for safety, commercialization and reimbursement. In contrast, mRNA molecules are normally short-lived and exert transient effects on cell biology. Thus, for some applications, mRNA is an important alternative to DNA-based therapies, with potential advantages for safety, re-dosing and commercialization.

Current Trends in Neurodevelopmental and Rare Pediatric Disease

Scott Hunter, PhD, Senior Scientific Expert, Neurodevelopment Disorders, WCG

In 2023, there will continue to be an emphasis on developing new outcome measures that can be used across rare pediatric and central nervous system (CNS) diseases. This has been an area of shared concern among caregivers regarding challenges observed with their impacted children that affect both individual and family engagement and quality of life. Moving from broader cognitive measures that are often experienced as less sensitive, focus has moved more to communication (specifically receptive and expressive language skills in such areas as Fragile-X, Angelman, Rett, autism spectrum disorders) and motor control (e.g., Rett, Angelman, Fragile-X).

Seeking greater sensitivity with scales developed, foundation and patient advocacy partners are developing mechanisms to build disorder-specific scales to address key areas of caregiver and patient concern while also collaborating across indications to support better measurement design. The goal of this is to amplify acceptance by the FDA of caregiver and clinician report measures and patient reported outcomes in the rare disease space.

We will move toward using wearables and engaging more directly with samples collected from these technologies that can be reviewed and rated by experts. Collecting simultaneous biological and behavioral outcomes through direct movement assessment, recording of communication efforts and video monitoring of responses, provides significant multipoint data that can be aggregated in tandem with use of performance measurements in rare and neurodevelopmental disease.

Neuroscience Research Trends to Pay Attention to in 2023

Mark G. A. Opler, PhD, MPH, Chief Research Officer, WCG Endpoint Solutions

The past five years have brought a remarkable burst of innovation in neuroscience drug development: approval of the first rapid-acting agent to treat depression, the past year’s massive surge of activity in the study of psychedelic compounds and the ongoing exploratory use of wearables and other technology-oriented methods for data collection. In the coming year, we’ll see some of these exciting yet unproven innovations begin to demonstrate their promise in a more substantive way with enduring, real-world impacts.

A few of the most important trends to watch include:

• Late-Stage Studies of Psychedelics and Cannabinoids: The first large-scale, phase 3 industry-sponsored studies of psilocybin by Compass Pathways should help prove the viability of the psychedelics movement in neuroscience. The published results of the Compass phase 2 program, if confirmed in phase 3, would solidify this while also clarifying the direction that this exciting new class of treatments is likely to take in years to come.
• Development of Wearables and Digital Biomarkers: Although regulatory agencies have held off on explicitly approving the use of novel endpoints related to wearable devices or similar device-rated digital biomarkers, the proliferation of these tools as exploratory endpoints is creating a growing wealth of data. As the evidence base for them continues to grow, standardization and adoption will almost certainly follow.

Epilepsy Treatments and Research: Where We Started and Where We Are Heading

Mike Cioffi, Senior Vice President, Clinical Solutions and Strategic Partnerships, WCG

Currently, there are more than 30 antiseizure medications (ASM) available to clinicians to treat patients. But even with such a significant amount of treatment options, more than 30 percent of individuals still do not respond to common ASMs and are addressed as “drug-resistant.” This will drive innovation in both pharmacological and nonpharmacological interventions aimed at improving symptoms and quality of life for patients along with their caregivers.

Research is ongoing in many areas, and we will see important advances in the field in the coming years. An increased application of technologies to aid in epilepsy management is likely. Smartwatches that can detect imminent seizures and alert caregivers to the location of the patient, and apps that can inform clinicians with real-time information on their patients’ status and seizure counts are all on the horizon.

Precision medicine has begun to take a more prominent role as we understand more about the pathogenesis of epilepsies. Significant advancement has been made in identifying the genetics of epilepsies, and the discovery of gene mutations responsible for a large portion of patients with developmental and epileptic encephalopathies.

Additionally, the search for biomarkers to guide drug development is moving at a fast pace and will potentially allow clinicians to improve diagnostic accuracy, predict response to ASMs and improve outcomes for patients.

While there are certainly limitations to current technologies and biomarker identification, and despite precision medicine being further researched, this multidisciplinary approach will redefine our ability to improve the treatment and management of epilepsy in the future.

Read the full WCG 2023 Trends and Insights report here: https://bit.ly/3XmcKC6.

Join WCG experts in a panel discussion of 2023 trends and insights in a Jan. 24 webinar. Register for the free webinar here: https://bit.ly/3GFXU2u.