概要
腳本/專家小組成員
Ms Norial: Hi everyone and thank you for joining our Novotech presentation on Asia Pacific: The solution for accelerating your clinical trial program. By way of introduction, my name is Katrina Norial and I am a Business Development Associate based in Boston. I’ve been working with Novotech for nine years and prior to joining our business development team two years ago, I was a senior lead CRA in a clinical team based in Sydney, Australia. With this experience, I understand the processes in conducting clinical trials in the region from ethics submission to managing trial sites, as well as meeting sponsors’ needs in executing their clinical trial strategy.
First, a brief introduction on Novotech. Novotech is a full service CRO specialise in the Asia Pacific region. We have on-the-ground operations across 12 geographies including China, South Korea, Taiwan, Thailand, Philippines, India, Singapore, Malaysia, Hong Kong, Australia and New Zealand. We cover a range of services for your clinical development needs. This includes feasibility activities, medical writing, protocol development, regulatory affairs, clinical project management and monitoring, medical monitoring, data management, biostatistics, safety services, vendor management and quality assurance. We also have a BioDesk team, which is our regulatory and consulting arm to support drug and clinical development planning.
Novotech provides best-in-class technology solutions and we have invested in all of the major platforms recognisable, such as Argus, our safety platform. SureClinical, our eTMF, Oracle Siebel as our CTMS and we are fully certified in Medidata Rave, Inform and BDOC as the three primary eDC platforms we offer. As an Asia Pacific CRO, we work across all therapeutic areas including, but not limited to, oncology, rare diseases, neurology, infectious diseases, hepatology and respiratory diseases. Majority of the clients we work with are small to mid-size biotechs based in North America and Europe and we have managed over 1200 projects from Phase I to Phase IV. We are proud of the service that we provide and we have received the Frost & Sullivan Asia Pacific Biotech CRO Company of the Year award for four consecutive years and we recently received the Great Workplace 2020 certification.
Novotech is a subsidiary of Novotech Health Holdings which consists of two operating brands: Novotech and PPC. Together we employ approximately 1500 people in 21 offices across 12 geographies. In the US, we have a client-facing team which is our business development team located in the west and east coasts and the rest of our team are located in Asia Pacific.
One of the strategies is that we have experienced, local leadership and on-the-ground regulatory and clinical project team presence in all of the countries we operate. Our teams have in-depth understanding of the local clinical and regulatory environment and processes, in addition to having established relationships with KOLs and leading clinical trial centres in the region. A partnership with Novotech allows our clients to tap into the Asia Pacific region, which is dynamic and one of the fast-growing clinical research regions to conduct trials. Recognising this opportunity, biotech companies are increasingly including Asia Pacific countries in their clinical development programs.
We are aware that many of our sponsors’ ultimate goal is to get approval from the FDA or EMA. This is why Novotech has a speciality group called BioDesk. BioDesk is Novotech’s in-house global product development and regulatory affairs consultancy arm, comprising a pre-clinical regulatory group of CMC experts, toxicologists, regulatory affairs experts and medics who can assist you in your pre-clinical planning and strategy. Our BioDesk team provides a range of services such as non-clinical project management, chemistry and manufacturing consultancy, drug development planning, preparation of regulatory documents and clinical trial applications as well as agency interactions.
So moving on to our second point, ensuring clinical trial continuity during COVID-19. Asia Pacific has displayed a high level of clinical trial continuity during COVID-19 in comparison to clinical trial locations, such as United States and Europe who face continued challenges. According to Frost & Sullivan, less than 8% of clinical trials running in Asia Pacific has faced disruption because of the pandemic, while this ration was much higher in Europe and North America. For some clarity, 60% of oncology trials in APAC reported that they were still able to continue enrolment and recruitment normally during the peak of the pandemic, in comparison to 20% in the United States. Novotech has seen an increased number of sponsors explore Asia Pacific as a region due to the significantly reduced disruptions from COVID-19 and we continue to support many trials for risk mitigation reasons.
These graphs demonstrate the high level of site resilience and activities across Asia Pacific at the peak of COVID-19 compared to where we’re at today. We have observed the majority of activities including on-site monitoring, site initiation, patient recruitment, which previously slowed down due to local restrictions and lockdowns, which have since resumed to almost back to normal.
Novotech has also been providing a detailed country bulletin to sponsors in light of the pandemic. These bulletins provide a snapshot of the number of infections and deaths compared to the United States and provide an overview of the clinical trial landscape on a range of dimensions including ethics and governance, patient recruitment status and on-site monitoring. There is also a section on where we provide a high-level status at each of the top 10 sites in each location to give the sponsors and idea where there are disruptions or if certain activities are paused.
Our last point on the agenda is leveraging regional advantages to accelerate development. Australia is a popular destination of choice to run clinical trials. Australia has a fast regulatory pathway and offers a favourable R&D scheme for eligible companies. Starting with quality, the quality of clinical data produced in Australia is accepted by the FDA and EMA. In Australia, there are experienced research teams, outstanding investigators in world-class facilities at institutes and this provides a great clinical infrastructure.
Regarding speed and efficiency, in Australia you can expect a start-up timeline of six to eight weeks for private sites from ethics submission to site activation with a leaner submission package in comparison to the United States. I will be providing more details on this in the next slides. On the last point regarding cost, it is 60% cheaper to run a trial in Australia in comparison to the United States. This is due to a couple of reasons. One is due to the favourable exchange rate; US$0.70 equals AU$1 and the cost of running a trial is also marginally cheaper in Australia but perhaps the most popular cost-saving rationale is the R&D tax rebate.
In short, Australia gives companies who are conducting research and development 43.5% of all R&D expenses in the form of a cash rebate. This works across a wide range of industries but lends itself perfectly to the biotechnology sector. The sponsor would be required to set up an Australian entity and you company needs to make a revenue of less than AU$20 million per year. You would be charged 100% of the costs for R&D, but at the end of the year, you will be able to submit them to the government for reimbursement.
To point out, the R&D rebate should really be considered as icing on the cake, as a cherry on top. In choosing Australia as the destination for your clinical trials and not to be the driving factor. It also takes approximately four to six weeks to set up an Australian entity and Novotech actually does not provide this service but would be happy to recommend tax firms and to facilitate introductions.
So as mentioned, the submission package is much leaner in Australia compared to the United States. You would only need a protocol, an investigators brochure, consent form, patient materials if applicable, indemnity insurance, budget and a list of sites. Please note that the pre-clinical work requirement would be the same; these activities cannot be skipped or reduced, but only the number of documents required for submission would be less.
The documents will be submitted to the Human Research Ethics Committees, or HREC or EC and they are responsible for assessing scientific validity, safety, efficacy and ensure that the trial meets the ethical standards and guidelines. After the trial is approved by the EC, the Therapeutic Goods Administration, the TGA, which is the FDA equivalent in Australia, will be electronically notified and in five business days an acknowledgement from the TGA can be expected.
In Australia public sites, there is an additional step involving the RGO, research governance, which is a site-specific approval prior to notifying the TGA. This process takes approximately one month. To summarise, private sites can take about six to eight weeks from submission to approval and public sites can take about 12 weeks. In parallel to these submission activities, site contract negotiations can commence. While Australia is a great location to run trials, it’s also noteworthy to mention that Asia Pacific is a fantastic location as well to run trials due to lower trial density, large pools of patients, high number of active PIs and an efficient regulatory pathway.
So regarding resource availability, there are a high number of active investigators and it’s not uncommon that these investigators have obtained their medical degrees from the United States or Europe. This also goes in parallel to high quality. The quality of data that’s being produced in Asia are excellent. Culturally there is also a strong doctor-patient relationship and physicians are well regarded in the community. We have observed patients and doctors adhere to the protocol better, which minimises deviations and violations, which results in higher quality data and lower critical findings by regulatory agencies compared to North America.
There also have been a number of reforms in regulatory processes and timelines across Asia in recent years. The average regulatory timelines in Asia are between four to five months and many Asian countries are trying to be competitive in these timelines, therefore updating their current regulatory processes. For example, in China historically it would take 18 months from submissions to first patient in and due to reforms, this has been reduced to eight months through reduction of bureaucratic processes.
In continuation from the previous slide, Asia Pacific is a preferred location due to the higher recruitment rates for complex trials. Each Asian country offers their community a different level of government spending on healthcare, including standard of care and drug reimbursements. How this benefits the sponsors is, for example, a patient may not have access to a drug or cannot afford it, therefore will actively look for clinical trials to participate. Also we have observed that patients may be treatment naive, so depending on your clinical trial program, this may actually be of benefit.
Moving on to the middle graph, this graph shows that Asia Pacific has a lower clinical trial density compared to the United States. Asia Pacific represents 60% of the world’s population with 1.4 billion people living in urban centres, meaning access to a large pool of patients. Again, the KOLs are excellent, often English speaking and eager to be recognised on the world scale, therefore quality of data produced is high.
To put everything we discussed in perspective, we had a sponsor interested in running a global Phase III study for small cell lung cancer. Our strategy was to initiate Australia first to take advantage of the first regulatory pathway to meet the first patient enrolled milestone. In parallel, we were submitting to the regulatory agencies in Asia. The involvement of sites in Asia allowed to accelerate patient recruitment with a complex protocol and in the end we were able to recruit 84 patients over 12 months, with South Korea amongst the largest contributors to the study.
So to recap, Novotech is a full service CRO, specialising in the Asia Pacific region. Asia Pacific has experienced less clinical trial disruptions during the COVID-19 pandemic and has since demonstrated a return to normalcy in clinical trial activities. Australia offers quality, speed and efficiency for clinical trials and the Australian Government are able to reimburse eligible companies 43.5% tax rebate for all R&D clinical trial expenses completed on Australian soil. Asia is home to 60% of the world’s population, with a lower clinical trial density and access to higher recruitment rates, with a large pool of investigators producing excellent data.
Thank you.