FDA Approves First Gene Therapy,

Betibeglogene Autotemcel (Zynteglo),

for Beta-Thalassemia
M. Alexander Otto, PA, MMS
August 17, 2022
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The US Food and Drug Administration (FDA) has approved the
gene therapy betibeglogene autotemcel (Zynteglo) for adult and
pediatric patients with beta-thalassemia who require regular red
blood cell transfusions.
Beta-thalassemia causes a significant reduction of hemoglobin
or the absence of hemoglobin altogether, owing to mutations in
the beta-globin gene. Patients typically require transfusions
every 2–5 weeks. The median age of death is 37 years.
Betibeglogene autotemcel, a one-time gene therapy, represents
a potential cure in which functional copies of the mutated gene
are inserted into patients' hematopoietic stem cells via a
replication-defective lentivirus.
"Today's approval is an important advance in the treatment of
beta-thalassemia, particularly in individuals who require ongoing
red blood cell transfusions," Peter Marks, MD, PhD, director of
the FDA's Center for Biologics Evaluation and Research, said in
an FDA press release. "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."
The approval was based on phase 3 trials, in which 89% of 41
patients aged 4 to 34 years who received the therapy maintained
normal or near-normal hemoglobin levels and didn't need
transfusions for at least a year. The patients were as young as
age 4, maker Bluebird Bio said in a press release.
FDA's Cellular, Tissue, and Gene Therapies Advisory Committee
unanimously recommended approval in June. The gene therapy
had been approved in Europe, where it carried a price tag of
about $1.8 million, but Bluebird pulled it from the market in 2021
because of problems with reimbursement.
"The decision to discontinue operations in Europe resulted from
prolonged negotiations with European payers and challenges to
achieving appropriate value recognition and market access," the
company said in a Securities and Exchange Commission filing.
The company has set the therapy's cost at $2.8 million but is
currently in negotiations with commercial payers as well as state
Medicaid agencies to improve timely access to care. That
includes reimbursing contracted payers up to 80% of the cost of
therapy if a patient does not achieve or maintain transfusion
independence up to 2 years following infusion.
The gene therapy will be available at bluebird Qualified
Treatment Centers, which the company says include
"preeminent transplant institutions" across the US.
"These Centers are critical partners in our mission for patients
and were selected not only for their exceptional 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
company's chief medical officer, Richard Colvin, MD, said in a
press release.
The company is planning an October 2022 launch and estimates
the US market for betibeglogene autotemcel to be about 1500
patients.
Adverse events in studies were "infrequent and consisted
primarily of nonserious infusion-related reactions," such as
abdominal pain, hot flush, dyspnea, tachycardia, noncardiac
chest pain, and cytopenias, including thrombocytopenia,
leukopenia, and neutropenia. One case of thrombocytopenia
was considered serious but resolved, according to the company.
Most of the serious adverse events were related to
hematopoietic stem cell collection and the busulfan conditioning
regimen. Insertional oncogenesis and/or cancer have been
reported with Bluebird's other gene therapy products, but no
cases have been associated with betibeglogene autotemcel.