새로운 표적, 접근 방식 및 조합으로 임상 결과 예측

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
• 약물 개발 가능한(druggable) 경로를 식별하기 위한 배경이 되는 병태 생리학을 어떻게 더 잘 이해할 수 있습니까?
• 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.

면역항암제는 표적 집단에서의 광범위한 암 치료과 관련된 약속을 이행했으나, 병용 요법을 통해 그러한 성공을 확장하는 것은 더 어렵습니다. QSP는 더 많은 환자 집단을 위한 더 나은 병용 요법 및 투여 요법으로 이어질 수 있는 유효성을 결정하는 복잡한 역학적 요인을 이해하고 통합함으로써 이러한 문제를 해결하는 데 매우 적합합니다.

Certara는 6개의 선도적인 제약 회사의 컨소시엄과 협력하여 가상 모집단 내에서 다양한 치료제 병용, 심지어는 다양한 방식을 사용한 약물까지 탐색할 수 있는 QSP IO Simulator를 개발했습니다. Simulator는 약물의 약동학, 표적 결합, 작용 기전뿐만 아니라 기저 종양 및 면역계 생물학에 대한 기존 지식을 통합하여 새로운 병용 요법 및 이중 항체 치료제와 같은 복잡한 생물학적 제제의 임상적 결과를 예측합니다. 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.