The consortium will address a major challenge of biologic drug development – predicting immunogenicity
Certara is launching a Quantitative Systems Pharmacology (QSP) Immunogenicity Consortium.
The company provides of decision support technology and consulting services for optimising drug development and improving health outcomes.
The consortium will use Quantitative Systems Pharmacology (QSP) to predict the immunogenicity of biologics and its impact on pharmacokinetics, efficacy and safety in diverse patient populations.
Modeled after the Simcyp Consortium, the QSP Immunogenicity Consortium will bring together biopharmaceutical companies in a pre-competitive space.
The aim is to develop an Immunogenicity Simulator that will predict immunogenicity of biologics and its impact on their pharmacokinetics, efficacy and safety in diverse patient populations.
Immunogenicity is defined by the FDA as the tendency of the therapeutic protein product to generate immune responses to itself and related proteins, or to induce immunologically-related adverse clinical events.
In a recent FDA review of 121 approved biological products, 89% of them had immunogenicity. In 49% of cases, this impacted their efficacy.
Immunogenicity is of particular concern for populations with compromised immune systems – often the very cohort receiving the biologic treatment.
Those involved in physiologically-based pharmacokinetic (PBPK) modeling and simulation to manage drug-drug interactions (DDIs) and dosing for special populations will be able to use these QSP models to manage immune responses.
“Our models and software tools will enable sponsors to manage immunogenicity by adjusting the biologic dose, route of administration, patient population and/or co-medications,” said Simcyp President and Managing Director, Steve Toon.
“It may also be possible to moderate the immune system’s tolerance of the drug.”
Professor Piet van der Graaf is Vice President and Head of Certara QSP.
“As immunogenicity to treatment is such a complex process, we need both QSP and mechanistic models of the humoral and cellular responses involved to fully understand it,” hr said.
He explained that current immunogenicity modelling uses machine learning to predict immunogenicity directly from the biologic drug’s genetic sequence.
“This is insufficient because it doesn’t account for the full complexity and dynamics of potential physiological responses or the differences between patient populations.”
Professor van der Graaf added that Certara will use a variety of structural, in vitro and in vivo input parameters for our dynamic models.
These will be implemented in an IT platform with a virtual patient simulator, which can be used to make development and regulatory decisions.
Along with the major regulatory bodies, most of the top 40 pharmaceutical companies – and all of the top 10 – are members of the Simcyp Consortium.
The consortium uses Certara’s Simcyp Simulator (PBPK) modelling and simulation platform to select the most appropriate drug doses, design optimal clinical trials.
They then use this data to evaluate new drug formulations and predict DDis and pharmacokinetic outcomes in clinical populations. Simcyp Simulator models are used extensively to inform drug label claims.
Mechanistic modelling of pharmacokinetics is now an expected component in regulatory submissions. Certara anticipates that QSP modelling will become a requirement as well.
The companiy's Immunogenicity Simulator is intended to inform clinical development for biologicals by allowing sponsors to explore optimal dosing routes and regimens and experient with various scenarios in the patient simulator.
Biologics currently comprise one third of all new drug approvals by the FDA.