Certain EU member states in Central and Eastern Europe still struggle to access chimeric antigen receptor (CAR)-T cell therapies compared to their Western counterparts despite regulatory approvals, say oncologists.

In June 2018, the European Medicines Agency (EMA) recommended the first CAR-T treatments in Europe—Novartis‘s Kymriah (tisagenlecleucel) and Gilead Sciences’ Yescarta (axicabtagene ciloleucel)—for approval. When it comes to the rollout of these therapies, EU states like Poland and Romania remain behind larger European countries like Spain, which have seen greater use. While access to these treatments is improving in some countries, as more CAR-Ts get approved, their high price point could prove challenging for healthcare systems with smaller budgets, say experts. Consequently, the steep pricing could push pharma companies to focus on larger countries, potentially slowing the rollout of these treatments in smaller countries.

Despite the EU’s efforts to tackle variable access across the bloc with initiatives like the European Cancer Inequalities Registry, CAR-T therapies could heighten inequalities, says Marius Geantă, president of the Center for Innovation in Medicine in Bucharest. Due to their high costs and logistical complexity, these treatments could require changes in healthcare models, especially in cases where there is not enough funding for them, he adds.

Central and Eastern Europe in different phases of catch-up

While CAR-T centers have expanded to several locations in countries like Czechia and Poland, which have also initiated funding schemes, other states such as Romania and Slovakia are still at earlier stages of adoption. Clinical sites capable of administering CAR-T therapies are being added in countries like Spain, broadening treatment access, says Dr. Fermín Sánchez-Guijo, professor at the Department of Medicine at the University of Salamanca, Spain.

According to the Organization for Economic Co-operation and Development, Central and Eastern European countries include Albania, Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, Slovenia. Excluding Albania, all of the listed countries are members of the EU.

In the Czech Republic, Dr. Petr Cetkovský, director of the Institute of Hematology and Blood Transfusion in Prague, says that the country‘s CAR-T program has caught up with its Western counterparts. News of Yescarta’s first administration appeared at the end of 2019, and Kymriah had its first use in a paediatric patient in April 2020. In proportion to the Czech population of more than 10.5m people, the number of patients who have been treated with CAR-T therapies is not “noticeably worse” than in Western countries, he says.

While there is a certain delay between when treatments that first become available in the US and when they arrive in the EU, availability then depends on the individual countries and their own processes, Cetkovský says. The FDA approved Kymriah in August 2017. Different governments, reimbursement agencies, pharma companies, and states make treatments available at different rates, he explains.

The Czech CAR-T program also benefits patients in the neighboring Slovakia. Since Slovakia does not have access to CAR-T therapies yet, patients in need of such treatments are sent to Czechia, Dr. Andrej Vranovský, physician at the National Oncological Institute in Bratislava, noted via email. There was no particular delay in getting CAR-T therapies in Czechia. They are now available in six centers across the country, with five aimed at adult patients and one at children. Even Slovakia will soon see the start of its own program, with the first patients possibly being treated with a CAR-T therapy at the National Oncological Institute this summer, Vranovský writes.

However, elsewhere in the region, CAR-T therapy use is still just beginning, as is the case in Romania, says Geantă. Romania’s approved the reimbursement of Kymriah in December 2020. However, the country still awaits its first patient to be successfully treated with the therapy, he says. South of Romania, at the Medical University of Sofia, Guenka Petrova, professor at the Department of Social Pharmacy and Pharmacoeconomics, writes that there is currently no access to CAR-T technologies in Bulgaria, citing pricing issues and a consequent lack of interest from companies.

Cost remains at the forefront of the CAR-T rollout, with some governments taking that into consideration. This is the case in Poland, says Dr. Maciej Niewada, professor at the Department of Clinical & Experimental Pharmacology at University of Warsaw’s Medical School, where the government included innovative treatments within its new PLN 4 billion ($895.2 million) medical fund, which was which was signed by the Polish president in October 2020. While Niewada says that CAR-T treatments are more likely to be covered since they are currently limited to relatively rare indications, access to such therapies in Poland is at the “very beginning” of availability. The first Yescarta CAR-T treatment was administered in late 2019. Additionally, six treatment centers in the country are offering Kymriah. Kymriah will be reimbursed for adults from next month, while it is being covered for pediatric patients since September 2021.

Meanwhile, Western countries such as Spain are seeing a “second wave” of new centers that are treating patients with CAR-T therapies, says Sánchez-Guijo, adding that this is seen across other EU states like France and Germany.

Despite this, Niewada says that there may be a delay in accessing such treatments in the region. However, this is the case for all expensive treatments, rather than just CAR-T therapies, he states, adding that “catch-up and uptake is generally slower”. According to Niewada, this is due to the treatments’ steep costs, which are more attuned to do business in Western European countries.

Sánchez-Guijo, who is also a vice-president elect for Europe in the International Society for Cell & Gene Therapy, says the introduction of CAR-T treatments is difficult because of not only the costs but also the need for the approval of each center by the pharma company. Cetkovský confirms that potential CAR-T centers need to be audited by the companies to make sure they are able to offer such treatments, which delays their rollout. At the same time, it is important to note that the auditing and preparation of potential centers adds a “certain amount of burden” on the pharma companies themselves, says Matthew Lakelin, co-founder of TrakCel, a provider of software solutions for the management of cell and gene therapy product delivery. As such, the company may not want to launch its product in every country, he adds.

Potential inequalities in the future

Any cost barriers may become an even greater issue as CAR-T treatments get approved in more common indications or in earlier lines of therapy, Cetkovský says. This issue will not only be limited to Central and Eastern Europe, and high-cost treatments for multiple myeloma or chronic lymphoblastic leukemia could potentially bring further strains on budgets. According to the European Society for Medical Oncology clinical practice guidelines, the estimated overall incidence of acute lymphoblastic leukemia and lymphoblastic lymphoma is 1.28 per 1 million individuals annually, while multiple myeloma has an estimated incidence of 4.5–6 per 100,000 patients a year in Europe.

Cetkovský cites a 2017 article cowritten by Dr. Mohamad Mohty, the former president-elect of the European Group for Bone Marrow and Transplantation (EBMT), to encapsulate this challenge, as it compared CAR-T therapy to a “narrow path between hope and bankruptcy”.

Different reimbursement approaches, such as the pay-for-performance model, could bring a change to the sector, says Romain de Rauville, vice president of Business Development at Exothera, a Belgian contract development and manufacturing company specializing in viral vector manufacturing for gene therapies.

That said, “harmonizing” access to treatments and the continued reimbursements remain a challenge, which could ultimately lead to differences in patients’ ability to get a treatment throughout the EU, says Sánchez-Guijo. According to the European Commission’s spokesperson, the agency has several plans and strategies to tackle such inequalities, including the launch of a pilot project on the market launch of centrally authorized products (CAPs). This project seeks to improve the knowledge of regulators on the planned marketing of CAPs and the reasons for delayed market launches, says the spokesperson. Still, Sánchez-Guijo says that it is important to see the initiatives in motion, rather than just being written.

Cell & Gene Therapy Coverage on Pharmaceutical Technology supported by Cytiva.

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