Long-Distance Rare Disease Trials: Why PLL Landed On Australia And New Zealand

By Jean-Pascal Zambaux, Cofounder and CEO, PLL Therapeutics

Conducting clinical trials for rare diseases, such as amyotrophic lateral sclerosis (ALS), is a complex, resource-intensive process. Trial location can influence patient recruitment, site activation timelines, regulatory processes, and access to specialized clinical expertise. In rare disease trials, these factors can affect the likelihood of completing the study on time, within budget, and with robust data. For us at PLL Therapeutics, a French clinical-stage biopharmaceutical company, Australia presented a combination of operational, regulatory, and clinical research factors that supported the decision to conduct the first stage of its ALS trial there. After completing Phase 1 in Australia, we are now preparing a Phase 2a/2b trial spanning Australia and New Zealand.

The Attraction Of Australia

In less than two years, following our initial encounter with the Australian delegation’s first-ever attendance at a bio event in Boston in 2024, we set up and successfully completed stage one of our first-in-human Phase 1/2 trial of ALS in Australia.  

We were struck by the speed in which the clinical study was implemented and conducted in Australia, crediting the country’s launch in 2025 of the Australian Clinical Trials Initiative (ACTI), a national program designed to build on Australia’s strong research infrastructure and streamlined regulatory processes while attracting more international studies. ACTI promotes Australia’s clinical research capabilities overseas, coordinates trade missions, and provides practical support to biotech and pharmaceutical companies considering Australia as a trial location. The initiative aims to improve access to innovative therapies for Australian patients and generate much-needed evidence in rare diseases, rare cancers, and other conditions with limited treatment options.

Australia’s focus on clinical trials, particularly in areas such as rare diseases where specialist expertise and efficient recruitment are essential, and its research infrastructure ultimately drove our decision to conduct our studies there. The extensive support the country offered more than offset the challenges of operating from Europe.

Regulatory efficiency and speed

Speed of approval is one of the most compelling advantages of conducting a rare disease clinical trial in Australia. In contrast to the FDA and EMA, where regulatory processes can be lengthy and bureaucratic, Australia’s system was streamlined, with approvals overseen by ethics committees rather than a centralized regulatory body.

The short timelines allowed us to secure approval for both Phase 1 and 2 trials in under six months, a stark contrast to the one to two years typically taken by European or the U.S. regulators. The ethics committees’ focus on science and patient safety, and its flexibility, allowed for quicker iterations and adjustments to our study protocols without the delays experienced in more rigid systems. We valued this efficiency particularly for our rare disease study in ALS, where death occurs three to five years after onset.

R&D tax incentives

Under the ACTI scheme, Australia offers a 42% R&D tax rebate, meaning we recouped nearly half of our R&D expenditures. For biotech companies, especially those with limited budgets, this financial incentive is very attractive. The rebate applies to clinical trial costs, placing Australia among the top most cost-effective locations for conducting research.

Skilled workforce and strong knowledge base

With a highly skilled workforce, particularly in neurodegenerative diseases, such as ALS, Australia has successfully developed a network of experts, including practitioners who have transitioned from academia and hospitals to CROs. Through this network of professionals with deep knowledge in the neurodegenerative field, established relationships with hospitals, and in-depth understanding of the logistical and scientific challenges of rare disease trials, we found it highly motivating to coordinate our clinical trial in Australia.

We also value the quality and experience of their local CROs, which specialize in small-scale, high-complexity trials. We chose a CRO with prior experience in ALS and stroke trials with leadership from institutions, including the Florey Institute of Neuroscience in Melbourne.

Australia maintains a strong and skilled workforce by retaining its talent with competitive opportunities to prevent brain drain to the U.S. or Europe. In addition, the healthcare system is actively working to attract researchers and clinicians from abroad, further strengthening its expertise.

Cost-effectiveness

Beyond the R&D tax rebate, Australia enabled us to conduct clinical trials at lower operational costs compared to the U.S. and western Europe. This includes everything from site fees to staffing and logistics. We found that the country provided a comparable quality of data and execution at a fraction of the cost of conducting the trial in France or the U.S.

Regulatory framework aligned with international standards

In Australia, our clinical trial is aligned with international regulatory standards, thus making it easier to transition our trials to other regions, which we plan to do through our Australian subsidiary, PLL Tx, as the sponsor of future Phase 3 trials, to include patients in the U.S., Europe, and, potentially, China. We anticipate that Australia’s reputation for high-quality data will help simplify our path to global approvals.

Additionally, Australia’s compassionate use programs are more flexible than those in many other countries, allowing for earlier and more streamlined access to experimental therapies for patients in need.

Patient recruitment

One of the surprising advantages of conducting a clinical trial in Australia for rare diseases is the country’s high prevalence of ALS (relative to the population). While the exact reason for the higher prevalence is unclear (potential genetic factors or environmental influences), we had a ready cohort of patients to participate.

The patient criteria for our Phase 1/2 clinical trial in ALS were highly specific (e.g., patients with high levels of inflammation). Despite the narrow focus, the principal investigator estimated that ~150 patients per year in Australia met the criteria, making recruitment feasible. We witnessed the hospitals play a proactive role in identifying and referring eligible patients, leveraging their existing networks and databases.

Challenges

While Australia offers many advantages, conducting trials remotely from Europe presented unique challenges.

Logistics and coordination

Managing a trial from afar requires meticulous planning and strong local partnerships to address:

• Site selection: The CRO identified hospitals across Australia (e.g., Calvary and Alfred in Melbourne, hospitals in Brisbane – Wesley and Sydney) with the infrastructure and expertise to conduct the trial.
• Drug distribution: The CRO coordinated the supply chain for investigational products, including labeling, packaging, and shipping to local pharmacies.
• Patient monitoring: Clinical staff administered the injections to patients at the hospital. This will differ in our Phase 2a/2b studies where patients will self-administer injections at home. We will partner with a nursing service to train patients, monitor compliance, and ensure proper administration.
• Sample collection: Blood and stool samples were collected, labeled, and shipped to France for biomarker analysis. This required specialized logistics to maintain sample integrity.

Cultural and operational differences

Contrary to expectations, we experienced minimal cultural barriers. We found the ethics committees in Australia are highly organized, with each hospital or region having its own committee. These committees replace the role of centralized agencies like the TGA or ANSM for trial oversight, focusing on ethical and scientific rigor.

In managing communications, we maintain weekly meetings with the local team, and I personally travel to Australia from France four or five times per year to align on milestones, address challenges, and foster relationships with the principal investigator.

Although we established subsidiaries in Australia and New Zealand, the teams are lean. They focus more on legal and administrative activities while the CRO and local partners undertake the bulk of clinical activities.

Future Outlook

We are looking ahead to conducting our Phase 2a/2b trials in ALS in the Pacific region, at sites in Australia, including Perth, as well as Auckland, New Zealand, where international clinical trials are rarely conducted. The Phase 2a/2b studies are designed to reflect our unique approach of targeting pre-symptomatic patients to protect motor neurons rather than treating them after damage has occurred, making our approach a first in ALS research.

Phase 2a will include 30 patients randomized into three arms (placebo + two dosages) with the primary endpoints being restoration of gut integrity (a key focus of our therapy) and reduction of inflammation. Phase 2b will enroll a minimum of 60 patients for an extended follow-up beyond the initial six-month Phase 2a trial and seek to explain the Phase 2a endpoints to include broader ALS progression metrics.

Lessons Learned Down Under

What would we do differently? Not much. The combination of Australia’s regulatory efficiency, skilled workforce, and financial incentives have shown to be a winning formula for us. For other biotech companies considering trials in Australia, here are some key takeaways:

• Leverage local expertise: Our partnership with local CRO Alithea Lifesciences, which has disease-specific experience, was critical. Their prior ALS and stroke trial experience streamlined site selection, patient recruitment, and logistics.
• Cherish the speed: Australia’s six-month approval timeline is a major advantage, as long as thorough high-quality documentation has been prepared.
• Take advantage of incentives: The 42% R&D tax rebate significantly reduces costs. Work with local advisors to optimize financial strategy.
• Build relationships: Regular travel and in-person meetings with principal investigators and ethics committee fosters trust and alignment.
• Plan for logistics: Long-distance trials require robust logistics for drug distribution, patient monitoring, and sample collection. Partnering with specialized service providers (nursing services, shipping, etc.) is essential.

Australia has been far more than just a location for us. Rather, the country quickly became a strategic partner that enabled rapid progress, high-quality data, and a pathway to global expansion. We consider Australia’s combination of regulatory efficiency, financial incentives, skilled workforce, and cost-effectiveness a compelling case for biotech companies to conduct complex trials.

About The Author:

Jean-Pascal Zambaux, cofounder and CEO of PLL Therapeutics, has a 30+ year career in the pharmaceutical and biotech industry. He created Disposable-Lab, a CMO specializing in producing injectable drugs for clinical trials, where he served as CEO between 2008 and 2018, and successfully ran the first pharma company to use a single-use grade A isolator for fill ‘n’ finish. He holds a Doctorate in Pharmacy (PharmD) earned from the University of Paris and the University of Reims, Champagne-Ardenne.