Pharmetheus
At the Cutting Edge Of Model-Informed Drug Development

A thorough drug development program is not easy to conduct; they take a considerably long time and remain a risky business despite the best of efforts. There are a lot of factors for drug developers to consider before the drugs are ready to be marketed. Every time a new medicine is developed, drug developers need to ascertain the cure’s efficacy and suitability for human use. Notably, this journey of a drug from early clinical trial all through to its approval can be further enhanced by the use of model-informed drug development (MIDD). The methodology involves the application of drug exposure-based, pharmacological, physiological, and statistical models derived from preclinical and clinical data sources. It can, thereby, reduce uncertainty around the drug’s efficiency, ultimately lowering failure rates and facilitating informed drug development and decision-making. And now, with the added impetus of the ongoing lockdown and social distancing norms, the lengthy drug development timelines have only prolonged further. Pharmaceutical companies are more than ever challenged in the generation of useful clinical data from diverse sources. To win this obstacle race, what pharma companies need is to embrace an MIDD approach.

Enter Pharmetheus. Based out of Sweden, Pharmetheus advances MIDD by helping pharmaceutical companies to design and augment their clinical studies with relevant data from other similar experiments. “We help our clients access the necessary knowledge regarding a particular drug and drive better clinical decisions, using data from a multitude of sources—be it similar past projects, ongoing research, or academic papers,” states Dr. Peter Milligan, CEO of Pharmetheus.

Unleashing the full potential of a quantitative approach to improving healthcare…

Interestingly, the name Pharmetheus is a wordplay on the Greek Titan Prometheus. According to the Pharmetheus team, while the Titan’s name means ‘the one who thinks beforehand,’ the company’s name stands for the one who thinks of ‘pharma.’ Pharmetheus started its journey in 2012 when a team of experienced consultants, leaders from the pharmaceutical industry, and researchers from Uppsala University (Sweden) came together to offer pharmacometric consultancy services and expedite drug development processes. Over time, Pharmetheus’ core business focus gradually broadened to support a wide range of reproducible MIDD services.

Dr. Milligan says, “We are transforming quality science into an informed decision.” To this extent, Pharmetheus’ offering comprises pharmacometrics, MIDD (including trail design), physiologically based pharmacometric modelling, quantitative systems pharmacology, and more, for a broad range of client types (pharmaceutical industry, charitable foundations, government and non-government agencies, and not-for-profit organisations).

Going the extra mile, Pharmetheus has developed a reproducible data reporting system that supports a fully traceable and auto-documented workflow for pharmacometric analyses—from source data to the final report

The Illustrated List of Pharmetheus’ Expertise

Even though the nature and extent of the services Pharmetheus provides are determined based on clients’ needs, pharmacometrics is at its core. For the uninitiated, pharmacometrics (within a Pharmetheus context) is an applied science where research and application interconnect both academia and industry. In this particular domain, academia develops a methodology to meet certain application needs, and the industry takes that methodology and turns it into a tangible application. Pharmacometrics, therefore, plays a crucial role in the broader sector of MIDD. “And Pharmetheus is at the crossroads of these activities and an active contributor in its own right,” highlights Dr. Milligan. As a result, Pharmetheus is able to adopt a broad range of quantitative approaches, in a fit for purpose manner. The company designs, conducts, and presents these pharmacometric analyses in the context of drug development, therapeutic, and regulatory decisions such as dose selection, study design features, etc.

Additionally, the company also supports trial design optimisation and expert advice in MIDD, clinical pharmacology, statistics, pharmacometrics, and regulatory strategy across the product lifecycle. Pharmetheus helps its clients develop the necessary drug, disease, and trial models for their clinical studies. The drug models describe the relationship between exposure (dose or PK related) and response (PD) for both desired and undesired effects and individual patient characteristics. Disease models describe the relationship between biomarkers and clinical outcomes, the time course of the disease progression, and placebo effects. The third aspect, trial models, defines the test group inclusion/exclusion and go/no-go criteria, along with patient discontinuation and adherence probability, based on probability of success.

In order to strengthen its capability and advance MIDD further, Pharmetheus offers additional services as a part of its hands-on modelling and simulation projects. From data management to report finalisation, Pharmetheus provides submission-ready reports and post-marketing analyses, characterised by traceability and accountability. Milligan notes, “From efficient routine analyses for complex systems to all the way through submission, we take pride in our timely and reproducible MIDD services.”

And making all this possible is Pharmetheus’ enthusiastic and dynamic team. The company has many recognised subject matter specialists to cover the technical and applied aspect of MIDD and enables the individual components of its deliverables.

Pharmetheus’ staff members include modellers (and non-modellers) from diverse, but complementary, educational and technical backgrounds, with extensive experience in both standard and complex pharmacometric analyses, and they possess illustrious joint experience in the drug development area.

The Added Layer of Cutting-Edge Tools and Methodologies

What’s more? In collaboration with its scientific advisors from Uppsala University, Pharmetheus uses cutting-edge tools and methodologies to enable fit-for-purpose deliverables for its clients. The company offers dedicated data programming support and has developed systems, processes, and tools to accommodate the dynamic nature of the drug development organisations and enable expeditious delivery of even the largest projects. Pharmetheus’ specialised data programming team empowers the client in creating analysis-ready data sets for a broad range of analysis types. The team supports the conversion of most data file formats, typically CDISC standard (SDTM, ADaM), Raw, and CSV, along with advanced data sets including repeated time-to-event modelling, Item Response Theory analyses of the composite score, or joint modelling of multiple responses such as PKPD with dropout. The data programming at Pharmetheus is performed in close connection with MIDD consultants with expertise in complex analyses and data file specifications. The Data Programmer and MIDD consultants also collaborate with an independent QC reviewer, ensuring a high standard of quality control.

“We help our clients access the necessary knowledge regarding a particular drug and drive better clinical decisions, using data from a multitude of sources—be it similar past projects, ongoing research, or academic papers.”

Going the extra mile, Pharmetheus has developed a reproducible data reporting system that supports a fully traceable and auto-documented workflow for pharmacometric analyses—from source data to the final report. To this end, the system leverages LaTeX and knitr document generation software. It helps create a submission-ready data programming report, which captures the entire data programming process. These report generating tools also enable real-time updates of analysed and source data if any changes are made to those. Dr. Milligan adds, “Altogether, our strength is to ensure our clients the supply of high-quality and timely deliverables, compliant with the latest regulatory standards.”

Towards a Better and Healthier Future

These proven capabilities of Pharmetheus have also made the company sought after amid the current pandemic. Many pharma companies are seeking Pharmetheus’ assistance in differentiating themselves by continuing their clinical trial programmes. Pharmetheus is also enabling pharmaceutical companies to reorient existing drugs to alleviate the symptoms and manifestations of COVID-19. The company is providing these clients with all the necessary data and disease models needed to repurpose the market available drugs. “And this is where we strive to create a difference,” comments Dr. Milligan. Moving ahead with its mission, Pharmetheus is now poised to rewrite the tenets of MIDD with cutting-edge technology and increase the productivity of drug development.