Norway: A destination of excellence for cell therapy trials

Norway was heavily involved in evaluating the world’s first commercial CAR T-cell therapy, Novartis Kymriah®, with Rikshospitalet and Radiumhospitalet (both part of Oslo University Hospital) as key sites for a total of four multinational clinical trials.

Dag Josefsen, Head of the Department of Cellular Therapy, Radiumhospitalet at Oslo University Hospital states, “We were selected for the studies due in large part to the high-quality reputation of our cell therapy departments.”

The strong performance across all four trials, in terms of patient recruitment, protocol compliance and quality of trial conduct, helped to establish the clinical and logistical foundation for implementing CAR T-cell therapy in Norway.

In 2018, shortly after the CAR T therapy gained regulatory approval, Norway was one of the first countries to implement and reimburse Kymriah, ensuring availability to all eligible children across the country.

Norway’s well-structured specialist healthcare system, combined with the population’s high willingness to participate in clinical trials, makes recruitment faster and more efficient. Radiumhospitalet, for example, was among the highest actively recruiting European centres in the CAR T studies.

Josefsen explains, “Norway has a relatively small population, but due to the way we are organised, we have access to many patients with the same kinds of diseases. In other countries it’s more dispersed among the local hospitals, but here it’s regionalised, so you have access to quite a big patient population.”

Sigrid Bratlie, Strategic Advisor at the Norwegian Cancer Society adds, “We have a good healthcare system and a good overview of the patient population.”

Norway has established, EU-compliant, certified cell therapy centres at all four major university hospitals: Oslo University Hospital, Haukeland University Hospital in Bergen, St Olav’s Hospital/Trondheim University Hospital, and University Hospital of North Norway in Tromsø.

Bratlie explains, “We have expanded the capacity for providing cell therapy to all the major hospitals in Norway. Being able to provide this treatment for patients in a decentralised fashion across the country is a milestone for Norway. It frees up capacity in Oslo to take on new cell and gene therapies, leading to even more approvals.”

“Numerous trials have been run in Norway, in particular, for multiple myeloma.I think that CAR T will become a therapy for solid cancers, not just haematological cancers. Next year at Rikshospitalet, there will be a CAR T trial for autoimmune diseases. This shows that these therapies have a much broader potential than in just oncology.”

In addition to a robust culture of collaboration, Norway has strong research environments supporting all steps of development for designing, producing and testing new immune cell therapies and which are dedicated to ensuring that innovations reach patients quickly. One of these is SINTEF in Trondheim.

Hanne Haslene-Hox, Senior Research Scientist at SINTEF, states, “Our goal is to move great science from academia to clinics, where we can apply it.”

“Norway has a high level of competence and flat hierarchies,” she explains, “meaning that highly trained people are more affordable. Since we are a small country, we have extremely close collaboration between technological institutes, academia and clinics. We are also a safe country with a stable government and a lot of experience in testing and implementing cell therapies all the way to the clinic. We can therefore offer quick turnaround and have the ability to take on ambitious projects.”

Norwegian scientists are at the cutting edge of cell therapy, using advanced technologies to achieve progress in development of cell therapies.

Haslene-Hox explains, “SINTEF, for example, employs methods like robotics, automation and high throughput technologies. Our operators use robots to automatically handle samples and cells, providing us with a much more efficient and robust system.”

“It is simply not possible to do such tasks manually when so many different things need to be tested at the same time. Using robots allows us to carry out 200-400 tests at a time and quickly identify promising results.”

“This, in turn, enables us to assess new parameters and ask questions we couldn't formerly ask, together with researchers and clinicians. We’re constantly asking ourselves, ‘How can we push the boundaries of what is possible?’”

Norway has established a Centre for Advanced Cell Therapy (ACT Centre) to support early-phase clinical trials for cellular therapies with the possibility for in-house cell manufacturing. Located at Radiumhospitalet, the centre aims to facilitate development of novel advanced therapy medicinal products (ATMPs).

The ACT Centre will guide clients through the necessary steps to transform a research product into a quality-assured product suitable for clinical trials. This includes support with regulatory requirements, process development, process validation and additional services as needed.

Josefsen elaborates, “We intend to take part in the in-house development and production of cells targeting specific indications. We have a few projects that are expected to be clinically ready within one to two years, with all production occurring internally.”

“We have already successfully produced genetically modified (GMO) cells at Radiumhospitalet. Led by Hanne Scholz, the first human, self-produced GMO-ATMP product was administered to a patient in a first-in-human clinical trial. It was a combination of CRISPR technology and viral vector – a very advanced technique – of which we are extremely proud to manage. The patient was treated in Uppsala, the ATMP product was manufactured in Oslo, and the viral vector came from the United States, so this was an intercontinental cooperation.”

In recent years, Norway has invested heavily in strengthening health research, including clinical trials, and will further develop the National Action Plan for Clinical Trials. In the most recent updates, clear instructions are provided to the regional health authorities and underlying agencies that clinical research must be an integral part of patient care.

When it comes to clinical trials involving advanced therapies, the Norwegian Government has taken steps to reduce regulatory hurdles, such as GMO regulations, ensuring speedy approvals on par with clinical trials in general.

Bratlie clarifies, “Although Norway is not part of the EU, it is aligned with the EU and bound by its regulations – so there is no difference regarding clinical trial regulations. Trials involving gene technology and GMOs are subject to more stringent regulations than standard clinical trials. Norway has been proactive in speeding up approvals by simplifying these regulations, which has been a key advantage. They have helped to overcome challenges in the implementation of numerous cell therapy innovations.”

In addition to increasing the number of clinical trials by 15 per cent annually, the Norwegian Government seeks to facilitate increased international and bilateral cooperation on health data and clinical trials.

Such cooperation will enable researchers in Norway and abroad to obtain access to more data and more patients, ideally accelerating progress and yielding improved therapies.

“Norway alone has had significant successes in both the areas of gene and cell therapy – solidifying its reputation as an outstanding clinical trial destination,” Bratlie points out.

“It’s important to consider Nordic collaboration in this field as well,” she adds. “In terms of patient recruitment, the individual the countries are quite small – but as a region we have a large population, which is quite attractive.”