Certara, a provider of decision support technology and consulting services for optimizing drug development and improving health outcomes, is launching a Quantitative Systems Pharmacology (QSP) Immunogenicity Consortium. Modeled after Certara’s Simcyp Consortium, and believed to be the first of its kind, the QSP Immunogenicity Consortium brings together biopharmaceutical companies in a pre-competitive environment to cooperatively 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 propensity of the therapeutic protein product to generate immune responses to itself and to 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 reported and in 49% of cases it impacted efficacy. Immunogenicity is especially concerning for vulnerable populations with compromised immune systems, oftentimes the exact cohort receiving the biologic treatment.

“Clients rely on Simcyp to research and provide cutting-edge solutions to understand and manage complex physiological drug reactions. Just as sponsors now use mechanistic physiologically-based pharmacokinetic (PBPK) modeling and simulation via the Simcyp Simulator to manage drug-drug interactions (DDIs) and dosing for special populations, they will be able to use these new QSP models to manage immune responses,” said Simcyp President and Managing Director Steve Toon, Ph.D. “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. It may also be possible to moderate the immune system’s tolerance of the drug.”

“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,” said Professor Piet van der Graaf, PharmD, Ph.D., vice president and head of Certara QSP. “Current immunogenicity modeling 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.”

“We will use a variety of structural, in vitro and in vivo input parameters for our dynamic models, which will be implemented in a robust IT platform coupled to a virtual patient simulator that can be used to make development and regulatory decisions,” added Professor van der Graaf.

Most of the top-40 pharmaceutical companies (including all of the top 10), along with the major regulatory bodies are members of the Simcyp Consortium, which uses Certara’s Simcyp Simulator PBPK modeling and simulation platform to select the most appropriate drug doses, design optimal clinical trials, evaluate new drug formulations, and predict DDIs and PK outcomes in clinical populations. Simcyp Simulator models are used extensively to inform drug label claims.

Mechanistic modeling of PK is now an expected component in regulatory submissions and it is anticipated that QSP modeling will become a requirement as well.

Certara’s Immunogenicity Simulator will help inform the clinical development for biologicals by allowing sponsors to explore optimal dosing routes and regimens, and answer ‘what-if’ questions in virtual patient populations.

Biologics currently comprise one third of all new drug approvals by the FDA. By 2019, they are predicted to generate $445 billion of sales revenue.