Meet the Expert - Clinical Pharmacology: Dr Simon Hutchings

As part of our ​‘Meet the Expert’ series, Strategy Director Steven Robery interviews Simon Hutchings, a Senior Clinical Pharmacologist at Weatherden.

Tell us a little about your background and your role here at Weatherden. 

My early career focused on preclinical pharmacology, mainly in vivo cardiovascular models, before I moved into clinical pharmacology, where I’ve spent the last 15 years or so. I was fortunate to work in a variety of environments – from Phase 1 units and CROs to investigator-led trials and biotech – before joining Weatherden as a Senior Clinical Pharmacologist in December 2023. 

At Weatherden, I help clients collect, analyse, and interpret human pharmacology data to support their clinical development decisions and applications for market authorisation. This might involve high-level strategic input into clinical pharmacology aspects of their development plan; contributing directly to clinical trial planning, oversight, analysis, and interpretation; or representing clinical pharmacology for regulatory agency interactions. 

One thing I love about my role is the variety of companies we work with. Our clients can be at any stage of clinical development, from preclinical candidate selection to Phase 3 studies, although most of the support I provide is in the First-in-Human to Proof-of-Concept stages. 

What is clinical pharmacology in drug development? 

Fundamentally, clinical pharmacology focuses on understanding the relationship between the dose (or dosing regimen), pharmacokinetics (PK), and the safety and efficacy of a drug. 

Importantly, it also considers the intrinsic and extrinsic factors that can affect this relationship. Intrinsic factors might include genetic polymorphisms of metabolising enzymes or even something as simple as age. Extrinsic factors might include food or other medications a patient takes at the same time as the investigational drug. 

Why is clinical pharmacology so important? 

I’d say the most important role clinical pharmacology plays is in guiding dose selection. Initially, this could include evaluating the intrinsic and extrinsic factors on the PK of a new drug to estimate a safe starting dose and a relevant dose range for a first-in-human clinical trial, followed by interpretation of the data to guide dose selection for subsequent Phase 2 and 3 clinical trials. 

From a clinical pharmacology perspective, what should emerging biotech companies consider when designing clinical trials? 

One of the most common requests I receive is to perform a gap analysis for a new client – what data they have, what studies they have planned, and what’s missing. It’s fine not to have all the data at a given stage in drug development, but having a plan for what will be required at each stage – even if the commercial strategy is for those studies to be performed by a partner in future – is important to understand the long-term plan. 

Another aspect I find is overlooked, particularly in early clinical development, is the use of modelling and pharmacometrics to support clinical development decisions. This might be the use of an appropriate PK model to estimate human exposure from preclinical, toxic, or kinetic studies; the use of physiologically based PK models to predict drug-drug interactions; or exposure response modelling to guide dose selection for Phase 2 and 3 clinical trials. 

What do companies most often get wrong without expert input, and how can it impact drug development? 

There seems to be a lack of consistency, particularly in the biotech sector, regarding how and when clinical pharmacology expertise should be incorporated into the drug development process. 

An obvious example is dose selection for a first-in-human clinical trial. In a recent instance, insufficient clinical pharmacology input led to an overly conservative approach to starting dose selection. The dose was based predominantly on toxicology and the no-observed-adverse-effect level, which is an older methodology for estimating an appropriate starting dose. Unfortunately, this led to an unnecessary number of cohorts being evaluated at subtherapeutic doses. This wasn’t a safety concern, but meant the company spent a lot of money and time on those dose levels. With clinical pharmacology input, they could have spent those resources further evaluating therapeutic dose levels and achieved the study’s objectives sooner. 

Another example is the FDA’s Project Optimus. Originally launched in in 2021, Project Optimus is an initiative for oncology therapeutics to ensure that each patient population receives an optimal dose. In the past, oncology drugs were largely cytotoxic agents developed using a Maximum Tolerated Dose (MTD) approach. Now, Project Optimus relies on the appropriate characterization of the relationship between exposure and safety and efficacy to guide dose selection. 

Increasingly, regulators expect evidence that the to-be-marketed dose included in a marketing authorization or New Drug Application is the lowest efficacious dose. If companies can’t demonstrate that their exposure response analysis is based on exploration of sufficient doses in early development, regulators may require them to redo Phase 3 studies to evaluate additional lower doses. That’s why it’s important to involve clinical pharmacology as early as possible in the drug development process. 

Curious about how clinical pharmacology fits into your strategy? Get in touch to learn how our experts can give your drug the best chance of success in clinical trials.