Asia Could be a Hotbed for Early Stage Clinical Trials
Dr. Melvin Toh, Vice President of Pharmaceutical Development for CK Life Sciences International, discusses the trends to detect early signs of efficacy. He also explains why early stage clinical work in Asia is still and sparse and what needs to be done to make it attractive.
Pharma IQ: Could you please outline the current development in early clinical trials globally?
M Toh: Due to the high attrition of drugs in clinical development, many initiatives have been introduced to try to improve the success rate. This has resulted in more sophisticated & demanding early-phase clinical trials.
Some of the more significant trends include the use of biomarkers to detect early signs of efficacy or to select patients more likely to respond to a particular drug. Increasingly, more early-phase clinical trials are also being conducted in Asia, with the realisation that differences in genetic background, diet and other factors may have an impact on the effectiveness and safety of a drug in Asian patients as compared to Caucasian patients.
Pharma IQ: In your opinion, what are some of the current capacity and gaps in early stage clinical trials?
Pharma IQ: Research facilities with good experience in early stage clinical trials are always in high demand, regardless of whether these trials are conducted in healthy volunteers or patients. For examples, even if you manage to place your study in a good cancer centre in the US for conducting Phase I studies in cancer patients, competition amongst studies is so high that enrolment slows to a crawl. There is a need to develop more sites with experience in early stage clinical trials, particularly in regions which are less saturated with clinical trial activity.
Big Pharma predominantly conducted their early stage clinical trials in the West, before including Asian countries in later phase clinical trials. Over the past 10-15 years, we have seen a significant increase in the number of early-phase clinical trials conducted in Asia, including First-in-Human trials where a drug has never been tested anywhere else in the world. Understandably, there was a lack of experience in the earlier days, but the experience and capabilities of researchers and research facilities have slowly grown.
Pharma IQ: When it comes to the development of early stage trials (phase 1 trials) what sort of expectation for growth is there in the next 5-10 years?
M Toh: My expectation is that there will be an increase in early stage trials involving biomarkers, e.g. PET imaging. More of these trials with involve regions outside US/Europe. Countries in Asia and other parts of the world will ramp up their research infrastructure and investment in human capital, to compete for a slice of the pie.
Pharma IQ: Why is early clinical work still sparse in Asia and is early clinical study riskier than other clinical development?
M Toh: In the early days, apart from lack of experience in Asia when it came to early clinical trials, there was also a need to gain the trust of Big Pharma sponsors.
Research infrastructure (e.g. dedicated hospital-based early research units, imaging facilities) was also lacking. There were also concerns about Intellectual Property protection. It was only after a couple of Big Pharma companies took a leap of faith and set up dedicated Phase I research units in Singapore, did the scene slowly change.
By slowing building up the confidence of pharmaceutical sponsors, early phase trials in Asia progressed from pharmacokinetic studies in healthy volunteers to First-in-Human studies in patients. Like all other clinical studies, patients/subjects are intensely monitored during earlyphase clinical trials to look out for safety concerns. In addition, before an early-phase trial can proceed, regulatory authorities and hospital Ethics Committees thoroughly review the preclinical data and other information to determine if it is safe for a clinical trial to commence. Dose escalation also proceeds slowly, starting from low doses and slowly escalating to higher doses if thought to be safe.
Pharma IQ: What is the pharmaceutical perspective to place study in Asia?
M Toh: Placing a study in Asia will allow you to collect pharmacokinetic/pharmacodynamic and safety/tolerability data from Asian patients early in the drug development process. Some regulatory authorities in the region are demanding efficacy/safety data specific to Asian patients before approving new drugs.
Having clinical data from Asian patients early in the process will allow companies to modify their clinical development plans as appropriate, to identify or exclude any differences between how Asian patients respond to new medicines as compared to Caucasian patients or patients of other ethnic groups.
Additional benefits of placing early phase clinical studies in Asia include: less competing trials at research sites, faster enrolment in some countries, highly motivated investigators eager to participate in early phase trials, as well as cost benefits.
Pharma IQ: What do Asian countries need to do to make Asia attractive to perform early clinical work?
M Toh: The research infrastructure in hospitals has to be boosted, as clinical trials become more sophisticated and demanding. It is also essential to train a critical mass of research personnel with the know-how to conduct early clinical research.
Regulatory Authorities and hospital Ethics Committees also need to gain the experience in reviewing information, like Investigational New Drug applications, and weigh the risks/benefits of allowing an early phase trial to proceed in their jurisdictions. In addition, as quick decision making is necessary in early clinical development, review and approval timelines of Regulatory Authorities and Ethics Committees can be further improved to make Asian countries more attractive for early clinical work.
Pharma IQ: Based on your prediction on how phase 1 trials will change in the next 5-10 years, what else needs to be done and more importantly, are we ready?And how will this impact clinical research in Asia?
M Toh: Several countries (e.g., Singapore & Korea) have already established themselves as good locales for early clinical research. With the growth in the pharmaceutical market in Asia and increasing demands of Regulatory Authorities for ethnic-specific data, we can definitely expect an increase in early stage clinical research conducted in Asia. More countries in the region will jump on the bandwagon, to position themselves to attract more early stage clinical trials into their countries. Asia is ready and waiting.