Efficiency of drug development methodologies

With the discipline of drug development under the industry microscope, NGP talks to two leading experts to find out what techniques are being employed to push the efficiency of drug development methodologies.

In your view, what are the main challenges currently facing drug development in the pharmaceutical industry?

Mark Richards. A look at the pipelines of big pharma reveals a significant number of small molecules and biologics in development for ‘solid tumours’. Currently, there is a paucity of methods to rationally link new targets to clinical settings where modulation can provide benefit. Without automated processes and standardisation, available methods can lack the reliability and reproducibility to make them suitable for drug development work. Additional challenges include identifying successful therapeutic candidates early and then subsequently selecting the patients most likely to benefit. Each of these could conceivably benefit from a well-designed and effectively implemented biomarker strategy from an early stage in clinical development.

Guy-Charles Fanneau de le Hoire. For the industry as a whole, productivity is too low and the enterprise faces multiple challenges: the cocktail of low productivity, rising regulatory demands and growing pricing pressure challenges the industry’s economic model and threatens innovation and the supply of new drugs. One can already see the result, with some companies choosing to invest outside the research-based pharmaceutical business to manage risk and sustainability. For small companies, these pressures translate into a difficult financing environment, independent of the impact of the broader context, so we need to be very disciplined in how we allocate the capital we have.

What tools and techniques can pharmaceutical and biotech companies use to maximise the efficiency of the drug development process?

GH. This depends very much on one’s starting point. At Neovacs, our lead product is to a very well validated target, TNFα, with an established huge market. But the benefits of this novel technology means that success with our approach will be a game-changer in TNF-mediated autoimmune disease. One approach to efficiency might translate into radical improvements in the approach to existing targets. Our second product is in lupus, an indication where clinical development has proven to be very difficult because of the heterogeneous and relapsing/remitting presentation of the disease. Here, we are planning to use a potential biomarker that might both be predictive of who might benefit from our drug and allow us to measure the activity of our drug early in the clinical trials process. Given the huge and growing costs of pivotal studies, as well as competition for patient recruitment, we need to find ways to make earlier studies as informative as possible.

MR. It seems clear that successful drug development programmes of the future will incorporate major efforts to identify and validate predictive biomarkers for response, toxicity, and other signals. As such, prospective collection, stabilisation and storage of patient samples – for example blood or tissue – could greatly assist this biomarker discovery process. Furthermore, as clinical research becomes increasingly global in its scope, the requirement for standardisation of techniques across trial centres through the use of automation becomes more important, to reduce variation and increase quality of data generated.

In response to the current challenges within the industry, many companies are choosing to focus their drug development efforts on areas of high unmet medical need. What are the potential benefits and drawbacks to such an approach?

MR. The advantages of targeting high, unmet medical need are clear: efficacious medicines that extend or improve quality of life are valued by patients and payers, and ultimately are able to command high prices. Many conditions are well-served by existing therapies and as such companies are faced with the law of diminishing returns – demonstrating improvements on standards of care becomes increasingly challenging. Focusing on areas of high unmet need is a way forward for many companies. Historically, successful drugs have addressed large homogeneous disease populations, and since the technology to efficiently select patients has been lacking, it has been either unfeasible or unprofitable to develop therapies for more ‘niche’ indications.

The decrease in pharma R&D productivity over time has been well documented and the drug development industry has yet to fully reap the benefits of the so-called ‘genomics age’. However, there are signs that this may be changing, and as we gain a greater understanding of the molecular basis of disease etiology and progression, a growing number of therapies have been launched that require companion diagnostic tests. This trend is set to accelerate; cost-effective, widely available molecular testing will facilitate development and approval of further targeted therapies.

GH. Areas of high unmet medical need are the natural target for the research-based biopharmaceutical industry. When we stray too far from it, it has undesirable regulatory and public perception consequences. Another benefit is that sufficiently high and unmet medical need may qualify a compound for regulatory preference mechanisms, leading to a faster route to market. At Neovacs, we are seeking to take advantage of these mechanisms by targeting our TNF product on patients poorly served by current TNF inhibitors; the level of unmet medical need in lupus also suggests that our interferon alpha product may be eligible for such consideration.

In terms of drawbacks, high unmet medical need typically translates into a major market opportunity and these areas are not secret, which means that there is always a very good reason why the medical need is unmet: specifically, meeting it requires a novel approach, which carries with it risk. However, taking and managing such risks is what the research-based biopharmaceutical industry does and we should be suspicious of short-cut business models.

How do you see pharmaceutical drug development changing over the next decade?

GH. Given the pressures on the enterprise, it is inevitable that there will be major changes in drug development, and we already see the large companies making very different bets based on their analysis of likely changes. I’d like to highlight one very important change we predict: There is going to much more focus on the affordability and cost effectiveness of therapies going forward and this will increasingly influence what gets developed. Even in the richest countries, politics aside, healthcare is rationed today, although the mechanisms vary from country to country.

Demographics make it inevitable that cost pressures in the rich countries can only grow. By contrast, many of the large pharmaceutical companies are increasingly interested in emerging markets as a source of growth: today this is mainly about expanding markets for existing medicines, but tomorrow the pipeline will be increasingly driven by the needs of these patients and affordability will be high up that list. The development of the traditional vaccine industry may provide a useful template as to some of the changes we may see in the therapeutics industry.

MR. I anticipate that progress in molecular testing will continue to permeate all stages of the drug development, including the trend towards development of companion diagnostics. This drives the necessity for coordinated bio-banking efforts whereby patient samples are extensively and routinely collected at multiple time-points in order to monitor disease and tailor therapy accordingly. A number of techniques are already available to track this monitoring of disease: real-time PCR and sequencing being two examples.

We can expect the proliferation of analytical platform installed bases to continue in drug development organisations and within community based pathology networks. In the short term, this would include systems for Pyrosequencing and real-time PCR, with more widespread and routine use of whole genome sequencing towards the end of the decade. As an innovation leader, QIAGEN is committed to advancing new technologies supporting personalised healthcare development. We will continue investing and working with pharmaceutical partners to make improvement in life possible.

Biography

After gaining a degree in Biochemistry from the University of Manchester, Richards started his career in oncology at AstraZeneca, Alderley Park. Subsequently he has worked in sales and marketing within the biotechnology industry, and currently oversees marketing activities for the QIAGEN pharma business in Europe and North America.

Prior to Neovacs, Guy-Charles was General Manager, Europe for IDM. Previously, he spent 8 years with Biogen, ultimately as a Vice President, leading International Regulatory, Medical and Marketing Operations. Previously, de la Hoire worked at Schering-Plough and Baxter. He started his career in the industry at Boehringer Ingelheim and holds a DVM from Lyon and an MBA from INSEAD.