Predict Clinical Outcomes for Novel Targets, Modalities & Combinations

In its July 2020 workshop, the US FDA described this modeling & simulation technology as shifting from “justifying the value of QSP”—to “best practices” implementation. QSP can help answer questions about the most novel compounds and modalities, combination therapy, initial dosing for first-of-its kind therapies, and other vexing development situations:

• In a given biological pathway, what is the best target and modality for pharmacological intervention to treat a given disease
• How can we improve the therapeutic effectiveness of an existing drug through combination therapy
• Can we predict human response (dose) to a novel mechanism based on preclinical data
• How can we better understand the underlying pathophysiology to identify druggable pathways?
• Can we predict the effect of a drug in a special population/other indication
• How can QSP support translation, product differentiation and utility of biomarkers
• Can we individualize dosing regimen based on patient characteristics
• How can we optimize clinical trials by accounting for pharmacodynamics interactions with comedications and genotypes

Certara is currently providing QSP consulting services and regulatory support to address the above questions, in therapeutic areas including oncology, vaccines, neurology, CNS, hematology, autoimmune disorders, rare disease, dermatology and gene therapy.

While Immuno-oncology has delivered on its promise for treating a wide range of cancers in targeted populations, the expansion of that success through combination therapy has been more elusive.  QSP is well suited to address this challenge, by understanding and integrating the complex dynamic factors determining efficacy that can lead to better combinations and dosing regimens for a wider group of patients.

Working with a consortium of six leading pharmaceutical companies, Certara has developed a QSP IO Simulator that will enable exploration of different therapeutic combinations, even drugs using different modalities, within virtual populations. The Simulator incorporates compounds’ pharmacokinetics, target binding, and mechanisms of action as well as existing knowledge on the underlying tumor and immune system biology to predict clinical results for novel combinations, and complex biologics such as bi-specifics. The Certara IO QSP platform is actively being leveraged for sponsor-specific projects.

Considered personalized medicine, each ‘therapy’ is based on individual patient data detail to repair or enhance faulty genes. Too low a dose might exclude that patient from any future benefit, while too high a dose can be very dangerous, since any immunogenic side effects may be irreversible and could last for years. Threading this needle requires a novel development approach.

Certara’s Virtual Twin-QSP platform has demonstrated success in multiple rare disease gene therapies in predicting and informing Phase I/II and III studies. We create a computer-simulated model of each patient (virtual twin), replicating the patient’s various attributes, including morphology that affect a drug’s fate in their body and hence its effects. Hundreds of virtual twins are simulated in virtual trials to evaluate the impact of different drug doses, schedules, and combinations so that we can predict an optimal dosing regimen for each patient.  Using this proven approach, we are working on AAV-based gene therapy; ex-vivo, in vivo and in situ; lysosomal storage; LNP-based RNA; gene editing; CRISPR/Cas9; and CAR-T technologies.