With the launch of Project Optimus, the FDA is reforming the dose optimization and dose selection paradigm in oncology drug development. Why? Poorly characterized dose and schedule may lead to selection of a dose that provides more toxicity without additional efficacy.
What does this mean for drug developers? Drug developers may have to:
- Redirect early clinical development objectives
- Re-think recommended Phase 2 dose justifications
- Understand and manage immunogenicity of biologics
- Assess impact on time and cost
- Navigate uncertain regulatory landscape and expectations
With deep experience in model-informed oncology drug development, dosing and regulatory strategy and submission, Certara has helped to advance hundreds of oncology programs. Our proven, integrated approach using quantitative methods can help you to navigate this regulatory change. The key lesson is to start early, including engaging with the FDA sooner than later.
Solutions to Help You Prepare for Optimus
Optimus Gap Analysis (clinical stage): Assess data, identify gaps in dose justification, provide decision support for dosages, review study design
Regulatory Engagement and Support: guidance on regulatory strategy, support in regulatory meetings, and regulatory writing & submission
Get the dose right the first time
Getting your dosing strategy right is now even more imperative with Project Optimus. How do we improve therapeutic response and lower the risk of toxicity for cancer patients? We believe that the best way to determine and refine your dosing strategy is through model-informed drug development. Our quantitative, model-informed approaches have helped to predict drug exposure and response, determine first-in-human dosing and optimize trial design, advancing hundreds of oncology programs.
- Dose finding using quantitative methods, such as Simcyp PBPK modeling and simulation or population PK analysis
- Clinical pharmacology gap analysis
- Early development, IND-enabling support
Navigate the changing regulatory landscape
It is essential to engage early with the FDA in this evolving environment. How? Our integrated team of regulatory experts provides regulatory strategy, consulting and submissions support to advance your program.
Regulatory Strategy: Increase your oncology product’s chance of approval with guidance from our seasoned regulatory experts specializing in regulatory intelligence, policy and strategy. With Project Optimus, the integration of model-informed drug development and regulatory strategy early on in development is critical to your success.
Regulatory Submissions: Without careful planning, anticipation of risks, expert execution and ability to navigate unexpected challenges, your oncology submission may fall off track. Rely on our around-the-clock support, expert team and advanced regulatory technology to support you every step of the way.
- Accelerated, Fast-track, PRIME and Breakthrough Therapy Designations
- Global and parallel submission preparation and leadership
- Regulatory writing powered by technology to increase consistency, quality and speed
Get the Simcyp Advantage
The Simcyp Simulator is the industry’s most sophisticated physiologically-based pharmacokinetic (PBPK) platform for determining first-in-human dosing, optimizing clinical study design, evaluating new drug formulations, setting the dose in untested populations, and predicting drug-drug interactions. The Simcyp Simulator has been used to inform more than 30 novel oncology drug approvals by the FDA. Using quantitative systems pharmacology, our IO and IG Simulators are state-of-the-art technology that help to inform critical decisions in oncology drug development.
Immuno-oncology Simulator: Our IO 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.
Immunogenicity Simulator: Our IG Simulator, adopted by the FDA and developed in partnership with 8 leading pharmaceutical companies, predicts immunogenicity incidence of therapeutics in development and potential impacts on pharmacokinetics and pharmacodynamics.
IND-enabling regulatory and drug development
The early drug development process is complex, and with Project Optimus, it is critical to work with an experienced team to deliver a robust first-in human (FIH)-enabling study design and regulatory strategy and meeting support. Our oncology experts support the full range of early development disciplines (ADME, bioanalytical, toxicology and drug safety, and CMC) for small and large molecules.
How are we different? Our deep expertise and quantitative approaches inform your most critical decisions with confidence. Since 2019, Certara’s services supported our clients as they have raised more than $65 billion in funding from venture capital and acquisitions
Get peace of mind now. Benefit from complete ADME packages as well as an optimized GLP toxicology/safety pharmacology and regulatory program tailored for Project Optimus to advance your IND.
Modeling and simulation for oncology dose evaluation
Modeling and simulation (M&S) approaches can improve dose selection and provide a risk-benefit assessment when developing an oncology drug. Considerations and analyses such as:
- PK sampling
- PK/PD relationships
- Exposure-response analyses
- Body weight-based dosing, and
- Food effect
help ensure the right dose is administered at the right time to the right patient.
Julie has over 10 years of drug development experience within the FDA. Dr Bullock’s past appointments include Clinical Pharmacology Team Leader and Senior Clinical Pharmacology Reviewer (FDA). Her regulatory experience was focused in the therapeutic areas of hematology/oncology and coagulation. She has unique insight in pediatric development, PK/PD approaches for biosimilar products, oncology dose finding strategy and streamlining development for breakthrough therapies and accelerated approval. Dr. Bullock has contributed to over 14 new molecular entity approvals during her 10-year FDA career.
Piet van der Graaf is Senior Vice President and Head of Quantitative Systems Pharmacology at Certara and Professor of Systems Pharmacology at Leiden University. From 2013-2016 he was the Director of Research of the Leiden Academic Centre for Drug Research. From 1999-2013 he held various leadership positions at Pfizer in Discovery Biology, Pharmacokinetics and Drug Metabolism and Clinical Pharmacology. He was the founding Editor-in-Chief of CPT: Pharmacometrics & Systems Pharmacology from 2012-2018 before becoming Editor-in-Chief of Clinical Pharmacology & Therapeutics. Piet received his doctorate training in clinical medicine with Nobel prize laureate Sir James Black at King’s College London. He has been awarded the 2024 Gary Neil Prize for Innovation in Drug Development from the American Society of Clinical Pharmacology and Therapeutics (ASCPT) and was the recipient of the 2021 Leadership Award from the International Society of Pharmacometrics (ISoP). Piet is an elected Fellow of the British Pharmacological Society and has published >200 articles in the area of quantitative pharmacology and drug development.
With a career spanning more than 30 years in the pharmaceutical industry, Steve has extensive experience across regulatory writing, consulting, and project leadership roles. He has successfully supported projects from discovery through approval and life cycle management, including holding significant roles in more than 75 submissions and, in several cases, leading the entire submission team, overseeing all documentation from Modules 1 through 5, publishing, and transmission to Regulatory authority.
Julie has over 10 years of drug development experience within the FDA. Dr Bullock’s past appointments include Clinical Pharmacology Team Leader and Senior Clinical Pharmacology Reviewer (FDA). Her regulatory experience was focused in the therapeutic areas of hematology/oncology and coagulation. She has unique insight in pediatric development, PK/PD approaches for biosimilar products, oncology dose finding strategy and streamlining development for breakthrough therapies and accelerated approval. Dr. Bullock has contributed to over 14 new molecular entity approvals during her 10-year FDA career.
Piet van der Graaf is Senior Vice President and Head of Quantitative Systems Pharmacology at Certara and Professor of Systems Pharmacology at Leiden University. From 2013-2016 he was the Director of Research of the Leiden Academic Centre for Drug Research. From 1999-2013 he held various leadership positions at Pfizer in Discovery Biology, Pharmacokinetics and Drug Metabolism and Clinical Pharmacology. He was the founding Editor-in-Chief of CPT: Pharmacometrics & Systems Pharmacology from 2012-2018 before becoming Editor-in-Chief of Clinical Pharmacology & Therapeutics. Piet received his doctorate training in clinical medicine with Nobel prize laureate Sir James Black at King’s College London. He has been awarded the 2024 Gary Neil Prize for Innovation in Drug Development from the American Society of Clinical Pharmacology and Therapeutics (ASCPT) and was the recipient of the 2021 Leadership Award from the International Society of Pharmacometrics (ISoP). Piet is an elected Fellow of the British Pharmacological Society and has published >200 articles in the area of quantitative pharmacology and drug development.
With a career spanning more than 30 years in the pharmaceutical industry, Steve has extensive experience across regulatory writing, consulting, and project leadership roles. He has successfully supported projects from discovery through approval and life cycle management, including holding significant roles in more than 75 submissions and, in several cases, leading the entire submission team, overseeing all documentation from Modules 1 through 5, publishing, and transmission to Regulatory authority.