FDA Approves Gene Therapy for Blood Disease

The FDA has approved Bluebird bio’s Zynteglo (betibeglogene autotemcel), also known as beti-cel, the first cell-based gene therapy to treat adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions.

Bluebird bio has set wholesale acquisition cost of $2.8 million for Zynteglo, and has set up an outcomes-based contract offering that includes a single upfront payment and up to 80% risk-sharing. Zynteglo will be available through a network of qualified treatment centers with experience delivering novel cell and gene therapies

Beta-thalassemia is a severe genetic blood disease caused by mutations in the beta-globin gene and is characterized by significantly reduced or absent adult hemoglobin production. This can result in severe anemia and lifelong dependence on red blood cell transfusions.

“Given the potential health complications associated with this serious disease, this action highlights the FDA’s continued commitment to supporting development of innovative therapies for patients who have limited treatment options,” Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, said in a press release.

Bluebird bio’s outcomes program includes a guarantee to reimburse contracted commercial and government payers up to 80% of the cost of the therapy if a patient fails to achieve and maintain transfusion independence up to two years following infusion. In phase 3 trials, all patients who achieved transfusion independence have remained transfusion free, the company pointed out.

Bluebird bio indicated that under the current standard of care, patients with transfusion-dependent beta-thalassemia require red blood cells transfusions every two to five weeks that can result in a lifetime cost of medical care of up to $6.4 million. Bluebird estimates the average total healthcare cost per patient per year is 23 times higher than the general population.

Tom Klima

“We have developed an equally innovative commercial infrastructure in collaboration with payers and providers, and with a focus on patients, to enable broad and timely access to Zynteglo for eligible patients and to support patients and families at every step of the treatment journey,” Tom Klima, chief commercial and operating officer, said in a press release.

One of the qualified providers is Point32Health, a not-for-profit health care organization formed by the merger of Harvard Pilgrim Health Care and Tufts Health Plan. “A one-time therapy with the potential to free patients from chronic transfusions may change the lives of countless patients and their families and transform the treatment paradigm for transfusion-dependent beta-thalassemia,” Michael Sherman, M.D., executive vice president and chief medical officer of Point32Health, said in a press release. “Point32Health is thrilled to collaborate with bluebird bio to provide access to this first-of-its kind therapy for our members who currently spend hundreds of hours each year managing their disease.”

Richard Colvin, M.D.

Richard Colvin, M.D., chief medical officer, bluebird bio, said the qualified treatment centers were selected not only for their clinical expertise in treating patients with beta-thalassemia, but for their practical experience with the specialized manufacturing and novel reimbursement associated with one-time therapies. The network includes established transplant centers from across the United States. Bluebird plans to onboard the centers on a rolling basis, with the first wave of centers trained and activated in September 2022.

Zynteglo is a one-time gene therapy product administered as a single dose. Each dose of Zynteglo is a customized treatment created using the patient’s own bone marrow stem cells that are genetically modified to produce functional beta-globin. The gene therapy gene therapy adds functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells.

It uses the Lenti-D lentiviral vector (LVV) — HIV type 1 cells that have had their genetic information removed — to add the beta-globin gene. Bluebird bio is conducting a long-term follow-up study, LTF-303, to monitor safety and efficacy for patients with TDT who have participated in bluebird bio-sponsored clinical studies of lentiviral vector gene therapy through 15 years post-treatment.

Related: FDA Advisory Committee Supports Approval of Gene Therapy for Blood Disease

This approval follows a June 2022 advisory committee meeting where members unanimously supported the approval of Zynteglo.

The safety and effectiveness of Zynteglo were established in two multicenter clinical studies that included adult and pediatric patients with beta-thalassemia requiring regular transfusions.

Effectiveness was established based on achievement of transfusion independence, which is attained when the patient maintains a pre-determined level of hemoglobin without needing any red blood cell transfusions for at least 12 months. Of 41 patients receiving Zynteglo, 89% achieved transfusion independence.