Last month, the US firm bluebird bio abandoned the sale of its gene therapy Zynteglo in Germany after a pricing dispute with health authorities — a blow that could have repercussions for the rollout of other gene therapies in Europe.
Zynteglo was approved in the EU in 2019 as the first-ever gene therapy for the blood disorder transfusion-dependent beta thalassemia. By early 2020, the company had made preparations with manufacturers, hospitals, and health insurers in Germany to roll out the treatment, with a huge price of over €1.5M per patient paid over five years.
However, the company recently revealed that the pricing negotiations in Germany had gone sour, with the health authority proposing a lower price than bluebird bio would accept. Hopes of commercializing Zynteglo in Germany have now been dashed.
The company remains optimistic over plans in other European countries to market Zynteglo, but its announcement was accompanied by plans to reduce its workforce, primarily in Europe. This accompanies yet another setback this year, where bluebird temporarily paused sales of Zynteglo and clinical testing of a similar gene therapy called LentiGlobin amid safety concerns.
The pricing dispute has raised wider questions over the viability of a European market for advanced treatments such as gene and cell therapies, which operate by inserting therapeutic genes or introducing functional cells into the body to offset the impact of defective mutations.
While potentially offering a lifetime of benefit from a single dose, these therapies often carry a hefty price tag that reimbursement systems may balk at.
“The bluebird decision in Europe has significance that goes beyond just the company and this particular indication,” said Brad Loncar, CEO of the US life sciences investment firm Loncar Investments. “It questions whether Europe will participate in the future.”
Gene therapies have had a rocky history since the first clinical trials more than two decades ago. The first generation of gene therapies included commercially unsuccessful candidates such as uniQure’s Glybera, which was withdrawn from Europe in 2017 due to lack of demand, and Strimvelis, whose poor sales led GSK to sell it to Orchard Therapeutics in 2018.
Another company currently rolling out a gene therapy in Europe is the Swiss giant Novartis, whose product Zolgensma was approved to treat spinal muscular atrophy (SMA) last year. The treatment raised eyebrows when it became the most expensive drug in the world with a one-off cost of around €2M per dose.
Gene therapies have now been joined by treatments that modify, replace, or remove disease-relevant DNA sequences using gene editing tools such as CRISPR/Cas9. The US firm Vertex’s CRISPR-based cell therapy CTX001, developed in collaboration with the Swiss company CRISPR Therapeutics, was the first of its kind to show disease-modifying activity in human patients in 2019.
Vertex plans to apply for approval of the therapy within two years for the treatment of sickle-cell disease and beta thalassemia and expects to target more than 30,000 patients in the US and EU. In the same week as bluebird bio’s withdrawal announcement, Vertex demonstrated its confidence in CTX001’s commercial potential by paying CRISPR Therapeutics up to €915M for majority control of the program.
Loncar pointed out that the first step towards the adoption of gene therapy has already begun, with support for the adoption of treatments for serious fatal conditions such as Zolgensma for SMA.
“The second step is these rare disease indications that are not necessarily immediately fatal yet are very serious like beta thalassemia and sickle cell disease. I’d say it’s not a great sign for the gene therapy field in Europe that it is getting caught up on this middle step.”
The final step would be the adoption of these therapies for broader indications such as hemophilia, said Loncar.
“Once that happens, we know that gene therapy has really made it to primetime. So I see a decision like Zynteglo being a fork in the road moment for gene therapy in Europe. Are we going to see gene therapy as a niche option for unique situations like SMA or are we going to see gene therapy realize its potential and change medicine in broad indications?”
Doug Danison, bluebird bio’s Head of Europe, acknowledged that the current reimbursement system presented challenges for one-off gene therapy treatments.
“We knew it would be challenging to introduce a one-time treatment to health systems designed to pay for chronic treatments, which have lower annual costs, but these costs must be paid repeatedly — sometimes for decades — making them potentially more expensive than a one-time gene therapy,” he told me.
Nonetheless, Danison remains optimistic that Zynteglo will have a future in Europe and points out that other countries have different approaches to Germany for evaluating and pricing treatments.
“We believe the benefits of Zynteglo will be recognized in other markets and that there is an understanding of the significant burden of chronic diseases to healthcare systems,” he maintained.
Cover image from Elena Resko