Simulator Technology Can Predict Optimal Vaccine Dosing

The development of drugs and vaccines is traditionally a long and expensive process, with more failures than successes. Before a preventive or therapeutic approach reaches patients, it must go through rigorous testing to confirm its safety and efficacy – determining the correct dose, dosing regime and administration route are all key considerations.

Certara is developing biosimulation and tech-enabled approaches to help scientists answer key questions at various stages of the development pipeline, serving to inform and accelerate the path to regulatory approval. One such approach, the company’s Vaccine Simulator™, can be leveraged across different therapeutic areas to determine optimal vaccine dosing and dosing regimens for different patient cohorts.

To find out more, Technology Networks spoke with Piet van der Graaf, senior vice president and head of quantitative systems pharmacology at Certara, and professor of systems pharmacology at Leiden University.

Q: For our readers who may be less familiar with Certara, could you tell us a little about the company history and mission?

A: Founded in 2008, Certara’s mission is to accelerate medicines using biosimulation and technology. Biosimulation uses computer-based tools to test drugs in simulated, virtual patients so that we can predict what a drug does in the body and what the body does to the drug, even before a human trial. The problem that we address is that traditional drug development takes too long and costs too much with a high failure rate. Using biosimulation, clinical trials can be made more efficient by reducing the number of patients enrolled and saving time, resulting in direct cost savings. There are even certain clinical trials that can be replaced altogether using biosimulation.

Q: What is quantitative systems pharmacology and what key questions can it help to answer

A: Quantitative systems pharmacology (QSP) is a biosimulation technology that combines computational modeling and experimental data to examine the relationships between a drug, the biological system and the disease process. QSP provides a framework for constructing mechanistic, mathematical models of drug action and can be used to help answer the following questions:

• What pharmacological action will a drug have in a particular organ?
• How can we improve the therapeutic effectiveness of an existing drug through combination therapy?
• Can we individualize dosing based on a patient’s characteristics?

QSP is especially valuable for new modalities, such as gene therapy.

We can also run computer-based virtual studies that may be impractical or unethical to perform with real participants due to a range of recruitment challenges such as age, concurrent diseases, or comedications. These virtual trials can be conducted using actual patient data and virtual patient data much faster and at a lower cost than live clinical studies.

Q: How can biosimulation be exploited to address key challenges and support decision-making during therapeutic development?

A: The fast-moving vaccine and drug development programs for COVID-19 have demonstrated how modern drug development approaches such as biosimulation can expedite the development of safe and effective medicines. At Certara, we are proud to have contributed to more than 30 programs on repurposed therapeutics, novel compounds and cocktails, and vaccines to fight COVID-19 with our customers. 

Specifically, one of the key initiatives we invested in early on in the pandemic was the development of a Vaccine Simulator, built based on our quantitative systems pharmacology, which allows researchers to study how vaccines, including those for COVID-19, are handled by the human body in computer-generated, virtual populations. 

Scientists used this Vaccine Simulator to conduct computer-based trials with different virtual populations to determine for example, which vaccine dose will generate the maximum antibody response for each age group. It can predict whether elderly people would be better served by receiving a higher dose of vaccine and whether younger people could generate a robust antibody response with a lower dose.

Earlier this year, our Vaccine Simulator predicted that the optimal timing between two vaccine doses for COVID-19 was eight weeks, which is approximately when the maximum number of memory B cells would be generated after the first vaccination. Just recently in July 2021, the Pitch study from Oxford University published results stating that an eight-week gap provided the best protection. We have also modeled the antibody response (or how many antibodies a person produces against SARS-CoV-2) over time, which shows that boosters should be given at approximately the 1-year mark after the first vaccine regimen.

Q: Can you discuss the importance of determining optimal dosing for different patient cohorts (e.g., elderly, pediatric populations, various ethnicities)?

A: A few decades ago, the industry followed a “one drug fits all” approach – drugs were designed for the “average person”. But this approach is not ideal because there are various factors that contribute to how drugs work in different people and getting the dosing regimen right for the right patient is critical. Even among children, the way an infant’s body handles a drug is significantly different compared to a teenager’s. Obviously, safety is paramount but so is efficacy in the dosing decision. Now we have more sophisticated tools to customize dosing for different types of people. Our biosimulation tools can model these different populations to determine the most appropriate dose and dosing regimen, which will be included in the drug label. For example, our Simcyp Platform has been used to inform more than 80 US Food and Drug Administration (FDA)-approved novel drugs and 250 label claims, providing specific prescribing detail for special populations.

Q: Can you tell us more about the company’s Vaccine Simulator^TM?

A: The power of our Vaccine Simulator is that it is a software platform that can be leveraged across different therapeutic areas, not just for COVID-19. The COVID-19 pandemic has generated significant momentum in vaccine development and innovation. Now we’re leveraging the simulator for vaccines being developed for cancer and respiratory syncytial virus (RSV). I am excited about the potential for our QSP technology and vaccine simulator to improve biopharmaceutical research and development productivity and impact decision making across the drug development lifecycle, from discovery, where we can inform drug target selection and validation, to throughout the clinical development phase.

Piet van der Graaf, PharmD, PhD, was speaking to Laura Elizabeth Lansdowne, Managing Editor for Technology Networks.