Medical science has moved on from the one-size-fits-all approach to the era of personalized medicine. European authorities approved the world’s first-ever gene therapy — GSK’s Strimvelis, a treatment for an inordinately rare inherited disorder characterized by a ravaged immune system, in 2016. So far, the EMA has granted the greatest number of marketing authorizations for advanced therapy medicinal products (ATMPs) —or medicines based on genes, tissues or cells — globally. But data suggest that the number of ATMP clinical trials initiated in Europe has been eclipsed by initiations in North America in recent years.

The analysis, conducted by a Washington DC and Belgium-based advocacy organization called the Alliance for Regenerative Medicine (ARM), included an assessment of active, interventional clinical ATMP trials initiated between January 2014 and June 2019 — as well as a survey of 22 ARM members, 16 of whom represent organizations sponsoring clinical trials in Europe.

Although there are roughly twice as many North America-based ATMP developers versus Europe, the number of clinical trial initiations in Europe is only about a third of those in North America, according to the ARM report.

“Most of the growth has taken place in North America and Asia and not so much in Europe…to me, that indicates that there is a lack of competitiveness compared to other regions,” said Annie Hubert, senior director of European Public Policy at ARM, in an interview with Endpoints News.

Regarding gene therapies specifically, there were proportionally more clinical trials (utilizing gene delivery, gene editing, and gene-modified cell therapy technologies) in North America versus Europe.

Altogether, these data substantiate what most ARM members have experienced over the last few years, Hubert said. ARM has about 350 members.

ARM has shared the data with some regulators, including the EMA and the European Commission, she added. “And I have to say that generally speaking, it wasn’t a big surprise.”

Clinical trial regulations across the pond
Unlike the United States, the European Union (EU) is a complex place to conduct clinical trials, no matter the type of therapy you want to develop. This is because if trials include patients in more than one EU country, drugmakers require authorization from each EU nation to conduct their studies.

This system, however, is in limbo. In 2014, the EU enforced legislation that harmonizes the assessment and supervision for EU clinical trials via clinical trial portal and database. However, repeated delays due to technical difficulties with the development of the IT systems have pushed the implementation to 2020-2021.

Dmitry Kuzmin 4BIO
“Gene therapy, in particular, is leaving that kindergarten phase of orphan and super orphan diseases, and going into what we call the medium-rare — so things are being tested on thousands and sometimes low hundreds of thousands of patients,” noted Dmitry Kuzmin, managing partner of London-based VC 4BIO Capital that focuses on advanced therapies.

“And if you think about those conditions, naturally, that would lead to multi-center trials across several countries because we’re not looking at the approvals on the back of 20-25 patients anymore. We’re looking at sizable clinical trials of up to 200 patients…this leads to just more trials in the US,” he said in an interview with Endpoints News.

Owen Smith 4BIO
The United States is also the biggest market for pharmaceutical products, noted Owen Smith, 4BIO’s director of investment. “With the harmonized access to so many patients in the US, it does make it favorable looking at companies with pipelines of assets and a number of rare diseases to be quite an attractive place to run those studies.”

“And I think some investors can be more nervous to invest in companies, which are running studies in different European places,” he added.

The process in the EU could get thornier once the fresh medical device and in vitro diagnostic (IVD) regulations kick in by 2022.

For sponsors who use diagnostics as part of their trials, or are developing therapies that must be delivered using medical devices, Hubert said, “the interplay between the clinical trial regulation and the IVD regulation is something that could be cause for complexity.”

Europe is also an anomaly because gene therapies are classified as GMOs in the region — requiring specific approval by GMO authorities, adding yet another layer of intricacy to the clinical trial initiation process.

Anne-Virginie Eggimann
The GMO application process is cumbersome and in some countries such as the Netherlands it can take a very long time, Anne-Virginie Eggimann, senior vice president of regulatory science at gene-therapy developer bluebird bio, told Endpoints News.

“It can take up to one year to get GMO authorization, in addition to your clinical trial authorization. Overall, if there has to be a GMO step, that’s okay. But it would be ideal if it could be aligned with the clinical trial timeline, joint with the same authority.”

ARM data shows that approval times for a new clinical trial in Europe vary from fewer than 30 days to more than a year, with an average approval time of three to six months.

In terms of trial initiations within Europe, some smaller countries are relative to their size, outperforming, such as Belgium, Denmark, and Switzerland, which attract proportionally more new ATMP clinical trials per capita than other countries, including North America. Meanwhile, Israel has the highest number of new ATMP clinical trials per capita in the world, the analysis suggested.

Most investors tend to overlook countries like the Netherlands, Belgium, Denmark, and Sweden, noted 4BIO’s Kuzmin. “People tend to discount smaller European countries as innovative…clinical trial ecosystems, but they actually can punch way above their weight.”

Source Endpoint News