Gene therapy in the real world: High priced, a long process and still relatively few patients | ASH 2025

Over the past several years, the flare of excitement about the new gene therapy treatments for beta thalassemia and sickle cell disease fizzled in disappointment because of the relatively small number of patients actually getting the ultra-expensive treatments after they hit the market. The flattering uptake has cast a shadow over the business prospects of some of the biotech companies that developed the pioneering therapies, especially Bluebird bio. The Boston-area company slashed staff and then earlier this year was acquired by two private equity firms, changed leadership and changed its name to Genetix Biotherapeutics.

The newly named company’s new chief medical officer, Joanne Lager, M.D., shared enrollment and treatment figures at a press briefing at the annual meeting of the American Society of Hematology (ASH) earlier this week that may assuage some concerns about the future of the pair of gene therapies for blood diseases but may still leave doubts lingering. According to charts Lager presented, less than 40 patients have been treated with Lyfgenia (lovotibeglogene autotemcel), Genetix’s gene therapy for sickle cell disease, and just 80 have been treated with the Zynteglo (betibeglogene autotemcel), the gene therapy for beta thalassemia.

But Lager’s presentation highlighted some numbers that suggest that the relative uptake of Lyfgenia has been faster than Zynteglo, even if the absolute numbers are smaller. For example, Lager said the time from FDA approval to the first patient being enrolled was twice as fast for Lyfgenia as it was for Zynteglo and that the six times as many treatment centers were “activated” during the first quarter after the launch of Lyfgenia than after the launch of Zynteglo. Zynteglo was approved by the FDA in August 2022, and Lyfgenia was approved more than a year later, in December 2023.

“We believe that our experience to date sets a benchmark for delivery and reinforces the value of these therapies to patients, providers and payers,” Lager said during the press briefing on Wednesday. Information presented at the briefing was embargoed until 7 a.m. this morning.

Zynteglo’s wholesale acquisition cost price (effectively the list price) has been widely reported as being $2.8 million and Lyfgenia’s, $3.1 million, making them two of the most expensive drugs on the market. Even so, some economic analyses have found the prices to be appropriate, partly because of the high costs of managing beta thalassemia and sickle cell disease with conventional medications. The high costs have been often mentioned as a reason for the sluggish adoption of gene therapies. But Lager said at the press briefing that payers are covering the therapies.

“We’re pleased to note that patients across the U.S. with public and private insurance are covered for these therapies, and while some documentation and negotiation is required, we have not seen a final denial for an enrolled patient,” Lager said.

Treatment with Zynteglo and Lyfgenia is a multistep process that involves stimulating the production of blood stem cells, collecting them, treating them with the gene therapy, ablating bone marrow to accommodate the genetically modified stem cells, and then infusing the cells back into the patient. Lager said it currently takes nine months for most patients to go from enrollment to treatment. She noted that most patients only require one collection of the blood stem cells; additional collections add 80 days to the process. “We’re working on ways to enhance mobilization, collection and manufacturing efficiency to improve the number of patients who only require one collection,” she said. Lager said the company was also expanding manufacturing capacity and streamlining manufacturing processes.

The abstract summarizing the timelines and other information discussed by Lager during the press briefing included data on patients only through July 1, 2025, whereas the charts she showed represented data midway through the fourth quarter. As a result, there are some discrepancies between the two. The abstract, which has Lager and other authors identified as Bluebird bio employees, says that 312 patients have been enrolled to be treated with Zynteglo or Lyfgenia, and of those, 77, or 25%, have been infused with the stem cells modified by gene therapy. The abstract says that after some statistical adjustment to account for the timing of the FDA approval, the average time between enrollment to receive the gene therapies and the collection of stem cells was 5.1 months. Another analysis suggested that some procedural delays drag out the treatment process. However, the abstract says the delays “may reflect not only logistical barriers but also the need for comprehensive patient and provider education.” 

According to the abstract, the time to infusion varied widely, from just 3.9 months to 17.9 months. The main factor in lengthening the time to infusion was the number of stem cell collections, the abstract says. Among the patients treated with Zynteglo, 11 (18%) of the 60 patients who were infused with the genetically modified stem cells needed more than one collection. Among the Lyfgenia patients, 4 of the 21 patients who had started collection at least six months prior to the data cut of the analysis required two or more collections. The abstract says that proportion is similar to clinical trial experience.

“Operational bottlenecks, such as coverage approvals, multiple collections, site readiness delays, and manufacturing capacity emerged as opportunities for targeted process improvement. Time to scheduled collection modestly increased over time, emphasizing the need for scalable workflows and coordinated planning,” the abstract concludes.