Articles

Like water in the desert - What the new M15 guidance means for QSP

Pharmetheus — Sun, 17 May 2026 10:00:00 GMT

Lourdes Cucurull-Sanchez

Principal Director, QSP Scientific Lead

A new ICH guidance on how to assess MIDD evidence integrated into drug development decisions has recently reached stage 4, bringing a common framework that regulatory agencies and drug developers around the world can begin to adopt.

One of the communities that will benefit the most of the M15 guidance are the QSP practitioners and users. The documentation, model development methods, data sources, model assessment and simulation settings for QSP analyses have been long-standing topics of uncertainty and discussion. This struggle was well documented in the proceedings of an FDA-Industry Scientific Exchange that took place virtually in 2020, where the need for a harmonized credibility assessment framework adapted to QSP practices was well captured.

A world without cancer

Pharmetheus — Fri, 15 Aug 2025 10:00:00 GMT

Is the end of cancer conceivable in the future? Is it possible to eradicate this disease from our bodies and our societies forever? The answers to these questions are embedded in the biology of this incredible disease.

These are Siddhartha Mukherjee’s words, from his extraordinary book ‘The Emperor of all Maladies’. They highlight the importance of untangling the biological processes that drive cancer if we are to find a cure.

But how do we connect those biological laws with the symptoms we observe in patients?

How to design a therapy that navigates those laws successfully? Out of all the quantitative sciences at our disposal to help us reduce uncertainty in this quest, QSP (Quantitative Systems Pharmacology) is the only approach that makes an explicit connection between drug, biology, and disease.

QSP is a reminder that drug therapies are a chemical intervention. Through QSP, we describe the dynamics of the chain reaction that follows downstream from the interaction between the drug and its target, all the way to changes in biomarker levels and clinical endpoints.

The initial medical practices were guided by the changes that doctors saw in their patients’ organs. Organs were the minimal functional units, because they were tangible to the naked eye. With the advent of new technologies, physicians can move from a macroscale to a microscale, examining cell levels (using microscopes and dyes) and then protein, RNA, and DNA levels (using -omics). QSP is often described as a ‘multiscale’ approach because it can be stretched to capture that continuum.

QSP is a reminder that drug therapies are a chemical intervention.

As a general assumption, for QSP, cells are the minimal functional unit in the human body. We can observe changes in cell functions via biomarkers. Whether a human is healthy or sick depends on how well interconnected, balanced, and synchronized the functions of all the human body cells are. We diagnose and monitor disease via biomarker changes in patients. Drug targets modulate cell function, and in turn, drugs modulate those targets.

The ability of QSP to deal with the dynamics of such a hierarchical system can mean different things to different kinds of drug developers. For bioinformaticians aiming to identify new molecular targets or novel combinations, and for molecular biologists seeking to validate them, QSP can be equivalent to a loss-of-function analysis or an in silico CRISPR experiment.

At the other end of the drug development process, for clinical scientists, QSP can serve as a means to enrich patient data with data derived from biological mechanistic knowledge. For principal investigators of clinical trials, QSP can give the key to identifying responders from non-responders, because it captures the biological diversity within our species.

To summarize, in the right hands, at the right moment, QSP can become a true enabler for Siddhartha Mukherjee’s plea – when the integration of biological and clinical knowledge leads us to the eradication of cancer and, by extension, of any terrible disease.

Adaptability and aptitude for learning — essential traits for future pharmacometricians

Pharmetheus — Tue, 03 Jun 2025 10:00:00 GMT

Pharmacometrics, a relatively young discipline using model-based methods for drug development, plays a vital role in internal decision-making and health authority interactions. However, the demand for skilled pharmacometricians currently exceeds the supply provided by academic institutions. Elodie Plan and Mats Karlsson took part in a group of experts, assembled by Peter Bonate, to provide insights in a publication in the Journal of Pharmacokinetics and Pharmacodynamics.

“As an industry, we recognize that even with more specialized academic programs, the demand for pharmacometricians is increasing beyond the access due to the broadening scope of applications”, says Elodie Plan, Chief Business Development Officer, and one of the founders of Pharmetheus.

Until recently she herself was to some extent involved in a great deal of the recruitments at the company:

“Building a company is as much about competence as it is about character. The culture we cherish is one of continuous learning, and sharing of knowledge. The ability to grow will be facilitated by recruiting people with potential to do just that: grow their scope, be agile and adapt to new circumstances.”

CAR-T cell therapy is part of the next generation of immuno-oncology treatment

Pharmetheus — Thu, 13 Jun 2024 10:00:00 GMT

Genetically modified T cells

Dr. Anna McLaughlin has dedicated her efforts to oncology, focusing on the model-based treatment optimization of targeted anti-cancer therapies, including CAR-T cells (Chimeric Antigen Receptor T cells), anti-hormonal drugs, and tyrosine kinase inhibitors.
– There has been a remarkable success of CAR-T cell therapy in treating aggressive hematological malignancies such as lymphoma. Although it is not limited to blood cancers, researchers are also exploring its potential in other cancers and indications, such as autoimmune diseases. The unique kinetic and dynamic properties of CAR-T cells, setting them apart from other therapies, add a fascinating yet challenging dimension to my daily work, Anna Mc Laughlin says.

Essentially, CAR-T cell therapy is a form of immunotherapy that modifies a patient’s own T cells to enhance their ability to target and combat tumor cells. This therapy starts by collecting the patient’s T cells through a process called apheresis. These T cells are then genetically modified in a laboratory to produce chimeric antigen receptors (CARs) on their surface, allowing them to recognize specific proteins found on the surface of tumor cells. Once the T cells are engineered with CARs, they are multiplied and reinfused into the patient’s bloodstream. These modified cells then locate and attack tumor cells across the body, effectively targeting and destroying them.

– A challenge is that up to 60 percent of the patients do not sustain a long-term response, so early prediction of response is crucial. Various factors have been linked to poor outcomes, for example, a high initial tumor burden or a low CAR-T cell maximum concentration, says Anna McLaughlin.

Education for empowerment: Online training in Clinical Pharmacology and Pharmacometrics in French

Pharmetheus — Tue, 21 May 2024 10:00:00 GMT

Foundational steps

Focusing on breaking linguistic barriers, the non-profit organization Pharmacometrics Africa, with support from Pharmetheus and French-speaking faculty professors, launched a French version of their online course in Clinical Pharmacology and Pharmacometrics. The program is tailored for French-speaking scientists within and from Africa and spans 3 months.

– Learning material in French opens doors for developing the scientific competencies within french-speaking Africa, Dr. Anna Chan Kwong says.

She works as pharmacometrician at Pharmetheus, and emphasizes the program’s significance and its important role in supporting the professional and personal growth of participants. Anna has been involved in the initiative since its beginning, starting with the translation of English learning material into an openly accessible French self-paced course, hosted on the Moodle e-learning platform by Pharmacometrics Africa. The progressions were demonstrated in a poster presented at WCoP 2022, and won the Impact award.

Subcutaneous drug delivery: PBPK-QSP model for absorption and anti-drug antibody response

Pharmetheus — Thu, 15 Jun 2023 10:00:00 GMT

Subcutaneous route and immunogenicity

The subcutaneous route of administration provides convenient and non-inferior delivery of therapeutic proteins compared to intravenous infusion. However, similarly to intravenous administration, there is a potential risk for undesirable effects such as anti-drug antibody emergence toward these therapeutic proteins [1].