Asia Pacific: The solution for accelerating your clinical trial program presented by Alex Ireland at OCT West Coast
Hi everyone, thank you for joining our presentation today where we will be discussing the Asia Pacific region as a solution for accelerating your clinical trials.
By way of introduction, my name is Alex Ireland. I am a Senior Business Development Manager based in the San Francisco Bay area. I have been working with Novotech for about three-and-a-half years, prior to which I was working in clinical operations for a small ophthalmology company in the Bay area, so I understand what it’s like working for a small company, cash strapped, wearing multiple hats and figuring out a strategy kind of as you move along. So really excited to talk about how we can help you with your clinical development program today.
First an introduction on Novotech. Novotech, we are an internationally recognised full service CRO. We are headquartered in Sydney, Australia, since 1996 and we specialise in the Asia Pacific region. So we have 11 offices through the Asia Pacific region in Australia and New Zealand, as well as South Korea, China, Hong Kong, Taiwan, Philippines, Singapore, Malaysia, Thailand and India.
As a full service CRO, we provide a comprehensive range of services that extends the full spectrum of your clinical development needs. This includes study feasibility, protocol development, regulatory affairs, standard clinical study management and monitoring, data management, biostats, medical writing, medical monitoring, safety services, vendor management and independent quality assurance. We provide best-in-class technology solutions to support your clinical trials as well, as you can see on the left-hand side of your screen.
As an Asia Pacific CRO, we do not limit ourselves to the therapeutic area, rather we work across all therapeutic areas, ranging from oncology and infectious disease, neurology, dermatology, we’ve done a long list of rare diseases as well and beyond. The majority of the sponsors that we work with are small to medium-sized biotech companies, often based in North America and Europe and we have been instrumental in the success of over 1200 studies, Phase I through IV, for these biotechnology companies.
We think we do a tremendous job, but our sponsors do as well. We have been the recipient of the 2020 Frost & Sullivan Asia Pacific Biotech CRO award for the fourth consecutive year in a row and we recently got a Great Workplace 2020 certification as well, which we are really proud of.
As mentioned, Novotech is the Asia Pacific CRO. We actually are a subsidiary of Novotech Health Holdings, which consists of two operating brands, Novotech and PPC. Together we employ about 1500 people in 21 offices in 12 geographies. You can see that we have a client-facing team in the United States, which is essentially the business development team, so everyone else is based in Asia Pacific. Of course, strategy to Novotech is that we have experienced, local leadership and on-the-ground regulatory and monitoring presence in each of the countries in which we operate.
So we have a director of clin ops, we have regulatory consultants, we have project managers, project directors, CRA. CTA, everyone that you would need in order to support your clinical trial in the countries in which we operate. We do have back-end services located in India, Malaysia and Australia. Our people do have an in-depth understanding of the local environment and excellent English language capabilities as we are an English-speaking company. A partnership with Novotech provides direct access to Asia Pacific, which is one of the most dynamic and fast-growing clinical research locations in the world.
As mentioned, we are an Asia Pacific CRO, however we are acutely aware that our sponsors’ ultimate goal is to get approval by the FDA or EMA. This is why we have created a specialty group within Novotech called BioDesk. BioDesk is Novotech’s in-house, global product development and regulatory affairs consultancy, comprising a CMC, manufacturing experts, toxicologists, clinicians and medics as well as regulatory affair experts who can help you with your pre-clinical planning as well as the strategy in between phases. They can provide a wide range of services, but for an example, they can provide you with non-clinical program management, chemistry and manufacturing consultancy, drug development planning, preparing regulatory documents, clinical trial applications, as well as agency interactions. They can be use separately from Novotech services and work on a project or hourly basis. We have a fantastic slide deck that I’d be happy to share with you, so please let me know if you would like more information on them. I have included my email address at the end of the presentation.
Current trends for clinician R&D. Over the past few years, we have seen a continued shift of R&D and innovation from your big pharma companies to small and mid-size biotechs. I’m sure many of you listening today used to work at a large pharma company and now have transitioned to a smaller biotech. On the left-hand side of the screen, we see biotechs are taking an increasingly large share of new drug approvals by the FDA. This shift suggests a few things, but emerging biotechs are retaining control of drugs they develop for a longer period of time and are holding off on the licensing and partnering deals smaller companies typically sign with pharma. This means these biotechs who are leaner, smaller and with less cash, need to get in and out of clinic faster. As we know, one of the best ways to do that is to increase your recruitment rates. Asia Pacific offers 60 per cent of the world’s population, often in dense cities, with lower number of competing trials, which we know contributes to increased recruitment rates.
Moving over to the right-hand side of the screen and starting at the bottom bullet, a lower number of competing trials is a motivating factor for 65 per cent of respondents. Faster than expected recruitment rates make for a positive clinical trial experience and as prior experience, an estimated 70 per cent of biotech respondents said that they would be likely or highly likely to involve the Asia Pacific region again for future trials. Which, in summary, leads to the top bullet point, that 42 per cent of respondents believe Asia Pacific will see a significant higher share of global activity over the months and years to come.
A record number in equity capital raised and a continued positive trend for R&D expenditure. In 2020 biotech companies have raised close to US$100 billion in equity capital. That’s a 70 per cent increase compared to 2019. No doubt with the introduction of COVID, the general public and investors have started paying significantly more attention to the clinical trial landscape. I’m sure those who work in clinical operations now have a much easier time explaining to your friends and family what you actually do. For me personally, I love that my friends and family are telling me how important a negative 70 freezer is and how logistically challenging the dissemination of vaccines are. This collective interest does underline the need for novel therapies and cost-effective R&D and small and medium biotech companies are paving the way for that future.
Ensuring clinical trial continuity during COVID. Although COVID started in the Asia Pacific region, they have displayed a high level of clinical trial continuity during COVID, as traditional trial locations such as the United States and Europe have faced continued challenges. According to Frost & Sullivan, less than eight per cent of clinical trials running in Asia Pacific faced disruption due to COVID, which is surprising, again, when comparing to the wealthier, more clinically tenured regions such as Europe and North America. In Asia Pacific, an impressive 60 per cent of oncology trials reported that they were able to continue enrolment and recruitment normally during the peak of the pandemic. I know personally I spoke with a large number of sponsors who were looking into contingency plans and risk mitigation strategies for their US and EU based trials during the high rates of COVID and the challenging clinical trial landscape that they continued to face as those regions were combatting high rates of infection and death.
Again, just to highlight the high level of site resiliency at the peak of COVID and continued to where we are today. We have observed high levels of site activity across Asia Pacific from monitoring site initiation in recruitment. Where there was a slowdown, we have seen that pop back up to almost normal, even as COVID continues throughout the globe.
COVID is unpredictable and Novotech has been provided anywhere from weekly, fortnightly, to monthly COVID bulletins on the status of COVID in the specific countries in which we operate. We provide a snapshot on the number of infections and death related to the United States. We provide general trial insights on the range and dimensions contributing to clinical trials, so feasibility, ethics and governance, recruitment, monitoring and the like. We also include a synopsis and a summary of how the top 10 sites in the particular region are doing just to give you an idea if there’s any disruptions in the sites, in the monitoring and I guess recruitment of these studies.
Leveraging regional advantages to accelerate development. Arguably one of the most popular countries to run a clinical trial outside of North America and Europe is Australia. Australia has a simple regulatory process and a very popular R&D tax rebate scheme that as well as it being an English-speaking country, makes it a great destination for clinical development. Starting with quality, the quality in Australia is absolutely accepted by the FDA and EMA. Australia offers a conducive ecosystem for clinical trials and seasoned research teams. We have over 50 independent medical research institutes and over 50 clinical trial networks, which provide a great clinical trial infrastructure.
Regarding speed and efficiency, in Australia the number of documents that are required for submission is leaner than what you would find in the United States and the application review process is much faster than what you would traditionally find in the United States. We’ll get into this in more detail onto the next two slides, but the quicker you can get into a clinical trial, saves you money. Therefore, if we go onto the fourth bullet point regarding costs, the number of documents required for submission and the submission process is faster, time is money, that saves you money. In addition, the power of the dollar is favourable to that of Australia, so US$0.70 equals AU$1.00. Then the cost of comparing clinical trials is marginally cheaper in Australia than in the United States, although it is getting more expensive.
But perhaps the most famous cost-saving rationale in Australia is the R&D tax rebate. So if you are a company that makes less than AU$20 million in revenue each year, which I’m assuming is most of you listening to this presentation today and you have set up an Australian entity, think like a Delaware corporation, then you can apply to have 43.5 per cent of all activity completed on Australian soil reimbursed. So to explain, you have decided to run a million-dollar clinical trial in Australia. You have your CRO, your investigator fees, your labs, drug depot, et cetera, that you have signed contracts with, they’re invoicing you throughout the entire year. Those invoices are paid 100 per cent, but then at the end of the year, you collect all your receipts from these vendors and then you apply to the government to have 43.5 per cent of those costs reimbursed. So your AU$1 million in direct and pass-through costs will be reimbursed $435,000 back to that Australian entity in roughly six to eight weeks. The rebate is a cash rebate; therefore, you can take the money back to United States, pay for your next year of clinical trials, there’s no real rules on how you spend that money.
A couple of points that I would like to mention before moving to the next slide. The research and development tax rebate should be considered the cherry on top, not the driving factor for why you go to Australia. You need a good rationale to go to Australia in the first place. The entity, which you will be required to set up prior to signing any contracts with CROs or vendors, takes about four to six weeks to set up. So take that into consideration before you want to sign any contracts with the CRO. Third is Novotech does not provide these consulting services, but we do have consulting firms that I’m happy to recommend. Again, my email will be at the end of the presentation.
There’s a lot of information on this slide, but to walk through it together, first, in Australia, the submission pathway for nearly all sponsors is via the Clinical Trial Notification Scheme, or CTN Scheme. In essence it’s a two-pronged approach to reduce the burden of submission, as well as decrease timelines for approval. The first is the number of documents required to actually submit to the clinical trial. So you only need a protocol IB, an ICF, patient-facing materials, insurance and indemnities, a budget and a list of sites. Please note that the pre-clinical work that you would be required to do in the United States would still be the same; you can’t skip or reduce that, but the amount of documents needed thereafter for the submission is much less.
The second way the clinical trial process is faster is by which it is approved, which is depicted on the bottom graph there. For both private and public sites, you will submit the documents, as we’ve just discussed, to the HREC, or Human Research Ethics Committees, or EC. The ECs, ethics committees, are responsible for assessing the scientific validity, safety and efficacy, the ethical acceptability of the trial and then ultimately approve it. After approving the study rationale and design, they will then inform the TGA, the Therapeutic Goods Administration, which is essentially the FDA equivalent, via an electronic notification scheme, which takes just a couple of business days.
There is an asterisk in there for the public sites in that between the ethics committee approval and TGA acknowledgement, there is a research governance, which takes about a month and is a site-specific governing body that requires the review and approval prior to TGA acknowledgement. Therefore, when we look at timelines, private sites take about two months and public sites take about three to three-and-a-half months for submission to approval.
A few comments on the timelines that I would like to overemphasise. Please assume at least one month prior to ethics committee submission for just general CRO start-up activities. That includes introductions to teams, kick-off meetings, getting systems in place, collecting essentially documents, et cetera. But often there is a two-week heads-up requirement to tell the ethics committee that you plan on submitting, that requires some time upfront. The second is private ethics committees often meet more frequently, so for example, Bellberry is a private ethics committee that has 12 committees with three meetings every Wednesday. So it allows a lot of flexibility in the submission process because if you just miss one week, you can go for the next. However, public sites tend to only meet one time per month, therefore if you do miss a submission deadline, there could be a month-long delay. The third is if you are planning to submit at the end of the year, Q4, early next year, Q1, please be prepared that there is a huge influx of companies that are trying to do the exact same thing. It is also during the Australian Christmas holidays and their summer holidays. So things, although don’t shut down entirely, they do slow down while competition increases.
Moving to the top graph where we prepare Australian versus traditional timelines, as mentioned before, time is money. Biotech companies without much funding are leveraging Australia’s quick CTN Scheme while in parallel submitting to the IND in the United States. This allows biotech companies to start accruing patient data while in parallel completing the IND package and the larger documents such as the IMPD and CNC documents that are required there.
Australia is a fantastic location to run clinical trials, but so is Asia. Asia Pacific is a preferred location for clinical trials because of lower clinical trial density, large pools of patients, high number of active investigators and efficient regulatory pathways. So to dissect this further, fast growing bio-pharma market, as Asia becomes wealthier, there is an increased number of middle class and ageing populations. As a result, we are unfortunately seeing higher rates of cancer and heart disease in this population. Resource availability, another consideration is the large pool of active investigators across the region. It is not uncommon for many investigators to go to school in the United States and Europe for medical school, work there for a few years before heading back home to be closer to family and serve their communities. So they're getting the same education and background than what you would find in the United States and Europe.
This also goes in parallel with higher quality, which is the second-to-last bullet point. These investigators have a strong desire to be recognised on the world stage and so the quality of data they produce is outstanding. In addition, culturally in this region there is a very high level of respect for physicians and a strong doctor-patient relationship. This means patients and physicians adhere to protocols better, meaning less protocol deviation and ultimately high quality of data. This has contributed to a lower rate of critical findings in both EMA and FDA inspections when compared to North America.
The last bullet point that I’ll mention on this slide is the favourable regulations. In Asia, the average regulatory timelines are between four and five months. In addition, many Asian countries are trying to become more competitive with other clinical trial destinations and so are revamping the regulatory processes and start-up timelines. Two examples, one, in 2018 we saw China do major reforms to their entire regulatory process. It used to take more than 18 months to achieve first base in China, but it has now been reduced to eight through a reduction of bureaucratic processes and an introduction of a pre-IND meeting, similar to what you’d find in the United States. The second example, Taiwan, is if you have another regulatory body such as the FDA or EMA or even the TGA approve a study, Taiwan’s FDA will piggyback off their due diligence and reduce the timelines by a month.
Continuing from, I guess, the prior slide, starting with the left graph, Asia offers higher recruitment rates for complex trials. Each Asian country offers their people a different level of government spending on healthcare, including drug reimbursement, as well as a standard of care. For example and how this benefits you, for example, you are an oncology company testing a combo therapy with a well-known drug A, plus your novel drug B. A patient sick with cancer might not have drug A in the country or cannot afford it or even an equivalent, therefore they will actively search for clinical trials to participate in so they can get access to the treatment, even if your drug B is still being tested. Also patients in Asia are more likely to be less heavily pre-treated which, depending on your study design, can be quite advantageous to your recruitment rates.
Moving to the middle graph, Asia is a lower clinical trial density region. Asia is home to over 60 per cent of the world’s population with very dense urban areas, meaning high accessibility to patients. To provide some context, in the United States there are 14 cities with more than one million people. In China there are more than 100 cities with one million people. In South Korea, there are nine cities with more than one million people and South Korea has a population 16 per cent of that the United States. Then again, the KOLs are fantastic, often English speaking and are eager to be recognised on the world stage, so the quality of data they produce is outstanding.
A case study bringing the information we have shared together; we had a sponsor that was interested in running a global Phase III study for the treatment of small cell lung cancer. As like many sponsors, they had an aggressive first patient screening milestone and completion of enrolment. Our country mix and strategy was to include Australia for the quick approval process to achieve that first-patient-in milestone, while in parallel we were submitting to multiple Asian regulatory bodies, such as South Korea, China, Thailand, India, Philippines and Malaysia. Once those countries that take a little bit longer with the regulatory process were up and rolling, we benefit from them because they have higher recruitments. So involving those Asian sites allowed to accelerate patient recruitment with a complex protocol. In the end, we were able to recruit 84 patients over 12 months.
So in recap, Novotech is a full service CRO headquartered in Australia and specialising in the Asia Pacific region. We are seeing a continued shift of R&D to small- and mid-sized biotech companies. As a result, time and cost efficiency strategies are of the essence. Asia Pacific has experienced less disruptions with clinical trial continuity throughout the pandemic. Australia’s CTN Scheme provides sponsors with a faster solution to achieve first-patient-in milestones, as well as the R&D tax rebate, which can reimburse sponsors 43.5 per cent of clinical trial expenses. Asia is home to 60 per cent of the world’s population who often live in very dense urban areas and with a low number of completing trials, offer high recruitment rates. And finally, Asia has a large pool of active investigators across the region who are eager to become KOLs and are producing high-quality data, including strong protocol adherence.
I know I’ve worked through a lot of information in a short amount of time. thank you again for your time for listening. If you have any questions or need further information, please do not hesitate to reach out to me. My email address is firstname.lastname@example.org and I look forward to hearing from you and how we can be a solution to your clinical trials. Thank you.