The pressure of looming patent expirations and the need for strengthened clinical development pipelines is driving the growth to address the demand of new medicines. In response to this pressure, the total number of molecules in development has grown consistently in recent years, with the largest growth seen in non-clinical drug development.
Here we talk to four Envigo scientists, all working in different areas of the non-clinical setting, to get their take on the current trends of drug development and how these strategies and technologies can help you get to market sooner.
1. Revised approaches to drug safety assessment are increasing the efficiency of the drug development process
Bringing a drug from discovery to market is costly and time-consuming, with every drug that fails being associated with an accompanying cost—which can be both reputational and financial. With an estimated total worldwide R&D spend of $US 141 billion in 2015, large pharmaceutical and biotechnology companies need to ensure they get an appropriate return on their investment—and to reach these goals it is estimated to require the launch of two to three new chemical or biological drugs by each company annually.
Recently there have been some revised approaches to drug safety assessment that can help increase the efficiency of the drug development process.
Steve Chrome, Senior Toxicologist at Envigo, explains, "Regulatory guidance, particularly the International Council for Harmonisation (ICH) guideline M3(R2), specifies the design of the non-clinical safety assessment package and the timing of its elements relative to clinical trials and regulatory milestones (Investigational New Drug Application, New Drug Application) for new chemical entities (NCEs). As a result, programs often have similar designs. However, many products now in development are biopharmaceuticals, and safety assessment of these molecules is different from that for NCEs."
Chrome continues, "With biologics, the required safety testing is more flexible, and designed around the product and the predicted safety issues resulting from the biology, rather than being a standard list of tests. This is because toxicity with biologics is, in the vast majority of cases, secondary to the pharmacology, whereas NCEs can have off-target effects that are nothing to do with the biology or pharmacology. Therefore, even though the non-clinical toxicology studies required for NCEs are heavily governed by regulation, extending those early studies and incorporating what has been learned from safety studies on biologics can help increase the effectiveness and speed of the drug development process."
Other strategies identified to improving the effectiveness of drug safety assessments:
- The integration of CV and CNS pharmacology safety endpoints into toxicology studies - a simple way in which high-risk drugs can be identified earlier in the development process
- Techniques like jacketed telemetry enabling quality assessment of cardiovascular and respiratory parameters as part of early-stage toxicity studies
- Incorporation of biomarkers earlier in development program—for example, as part of short dose range-finding studies—may aid earlier detection of toxicity
Explore the strategies and technologies improving non-clinical drug safety assessments in more detail.
2. Non-animal technologies in safety assessment is undergoing extraordinary growth
Globally, there is a rise in non-animal technologies (or alternative) (NATs) in pharmaceutical and chemical safety assessment. The National Academy of Sciences state 'Advances in toxicogenomics, bioinformatics, systems biology, epigenetics, and computational toxicology could transform toxicity testing from a system based on whole-animal testing to one founded primarily on in vitro methods that evaluate changes in biologic processes using cells, cell lines, or cellular components, preferably of human origin.'
Dr Brian Burlinson, Principal Scientist, Safety Assessment Europe, Envigo, says, "NATs is a phenomenon driven by regulation, political and social factors and advances in science and technology. It marks an exciting opportunity for drug discovery and development specifically—both in the advent of new approaches to toxicology and safety assessment, and to enhance drug discovery and selection."
The 'new' toxicology
Dr Burlinson explains that these drivers of change include the vision of the US National Academy of Sciences ‘new’ toxicology approach that would leverage advances in biotechnology in order to transform toxicity testing. As a result, NATs are now revolutionizing the drug development process and replacing existing in vivo methods with new in silico methodologies, and 2D or 3D in vitro assays.
In addition to alternative in vivo methods, culture systems of human tissue maintained in specialized micro-environments designed to replicate in vivo conditions now allow more physiologically relevant toxicology and efficacy assays to be performed in vitro.
Dr Burlinson adds that from a commercial perspective, integrating capabilities from across the drug discovery pathway and collaborating with contract research organizations (CROs) will support commercialization of NATs, providing a fast and effective way of delivering the 3Rs (replacement, reduction, refinement).
"What’s key to capitalizing opportunities is having an integrated approach, making the most of the expertise from different disciplines, and thinking creatively and collaboratively about the big problems that are still out there," explains Dr Burlinson.
Learn more about seizing new opportunities in non-animal technologies.
3. De-risking as early as possible continues to be highly effective
De-risking drug development represents a relatively new strategy designed to quickly assess if a new drug has a metabolic liability, making it potentially susceptible to being approved with restrictive conditions or labelling, being refused approval, suffering complex clinical development or being withdrawn from the market once it’s been approved for a wider population.
Guy Webber, Scientific Manager, In vitro and Drug-Drug Interaction sciences, Envigo, explains, "Essentially, de-risking provides confidence to invest in that molecule not only in terms of capital investment but also in terms of utilizing valuable resources such as time and people."
Webber continues, "Understanding the risk areas where molecules fail is critical. Through applying appropriate experimental resources to identify potential exposure to these risks early in the development process, will help identify molecules that have a better chance of survival and allow you to make better informed decisions regarding 'the likelihood' of risk, thus making the process of bringing products to market more efficient."
Learn more about what these de-risking risk areas look like by streaming our de-risking webinar series.
4. Large Pharma is reducing the size of in-house in vivo teams and looking towards contract research organizations
In vivo models of disease states are evolving, with more robust and complex study designs allowing the gathering of data for multiplex, clinically relevant endpoints. This allows maximization of the results to gain from each animal experiment, thus helping to reduce the usage of animals. A recent trend identified by Envigo's Principal Scientist, Steve Jordan, is that "large pharma has been reducing the size of in-house in vivo teams, with a greater reliance on strategic partnering with external contract research organizations (CROs)—partnerships that use integrated working between several disciplines to devise robust study designs and testing regimes that maximise the value of each in vivo experiment." In addition to this, outsourcing to a CRO could make the drug development process more efficient. In fact, ContractPharma found that in fully established strategic partnerships, speed-to-market could be accelerated by months and cost efficiencies could reach 25% to 30% relative to traditional transactional outsourcing.
Jordan highlights, "In our experience, the success of in vivo models requires collaboration between study scientists, customers and a range of internal disciplines, including pathology, surgery, formulation chemistry, bioanalysis, toxicology, and dedicated biomarkers. For respiratory models, we also include inhalation scientists, who can help support the study design for drugs intended to be administered by the inhaled route."
"With this outlook you have the flexibility to adjust and refine existing in vivo models, add additional, clinically relevant endpoints and validate these endpoints. Building bespoke studies is especially essential as it is rarely a case of 'off the shelf' combinations. Ultimately, not only will you have more flexibility with this approach, this will also be the key to getting to market sooner."
Learn more about the trends in in vivo models targeting respiratory disease.
If you're in the process of planning and conducting preclinical studies to move into the next development stage, read our article 'How to plan and conquer the drug development process in the early stages'.