Cells collected from 1st SCD patient receiving gene therapy Lyfgenia

After collection, stem cells are treated then infused via stem cell transplant

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Bluebird Bio has announced it’s completed collecting cells from the first sickle cell disease (SCD) patient receiving the gene therapy Lyfgenia (lovotibeglogene autotemcel), following its recent approval in the U.S.

The cells were collected at Children’s National Hospital in Washington D.C., which is part of the company’s national network of qualified treatment centers. The. centers are selected based on their expertise in cell and gene therapy, transplant, and SCD, and they receive specialized training on how to administer Lyfgenia.

“We are thrilled to be the first center in the country to commercially collect cells from a person living with sickle cell disease and are proud to be the trailblazers in using this new approach,” David Jacobsohn, MD, chief of the division of Blood and Marrow Transplantation at Children’s, said in a company press release. “The recent approval of gene therapies to treat patients with sickle cell is an enormous breakthrough in patient care and a silver lining to families witnessing their children’s struggles with this condition.”

Meanwhile, Minaris Regenerative Medicine, a global cell and gene therapy manufacturer, has announced the first commercial run of Lyfgenia at its facility in Allendale, New Jersey.

“The commencement of commercial manufacturing for Lyfgenia represents an important step for the cell and gene therapy industry as it will allow many patients fighting sickle cell disease to benefit from this new, potentially curative medicine,” Hiroto Bando, PhD, Minaris’ CEO, said in a separate press release.

SCD is caused by mutations in the HBB gene that lead to an abnormal form of hemoglobin, the protein in red blood cells that carries oxygen through the body, being produced. Defective hemoglobin tends to form clumps and causes red blood cells to acquire a sickle-like shape, which are prone to getting stuck inside blood vessels, restricting blood flow and reducing oxygen delivery to tissues. This can lead to episodes of acute pain known as vaso-occlusive crises (VOCs).

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How does Lygenia gene therapy work?

Lyfgenia is a one-time gene therapy approved last year by the U.S. Food and Drug Administration for SCD patients, ages 12 and older, with a history of vaso-occlusive events (VOEs), including VOCs and other sickle cell-related complications. It’s designed to provide patients with a modified HBB gene that produces a form of hemoglobin, called HbAT87Q, which is resistant to clumping.

The treatment involves collecting patients’ hematopoietic stem cells, or blood cell precursors, and treating them with Lyfgenia before infusing them back into the patient via a stem cell transplant. Before the transplant, patients must undergo a round of chemotherapy to eliminate faulty blood stem cells.

After the transplant, red blood cells generated from the engineered stem cells should produce the anti-sickling hemoglobin, limiting red blood cell sickling and potentially reducing the frequency and severity of VOEs.

Lyfgenia’s approval was based on efficacy data from 36 patients, ages 12-50, who entered the completed Phase 1/2 HGB-206 trial (NCT02140554), where all received the gene therapy.

Of 32 patients evaluated for the trial’s main efficacy goals, 30 (94%) had no severe VOEs and 28 (88.2%) had no VOEs after the treatment.

Safety data obtained for 54 patients who initiated the process of cell collection showed the most common side effects were inflammation of the lips, mouth, and throat, and low levels of blood cells.

The company is also conducting the Phase 3 HGB-210 trial (NCT04293185), which is evaluating the efficacy of the gene therapy in about 35 SCD patients, ages 2-50. The trial is ongoing.

A long-term safety and efficacy follow-up study, LTF-307 (NCT04628585) is also underway. It’s open to SCD patients treated with Lyfgenia in previous clinical studies sponsored by the company. The study will follow the participants for 13 additional years.

“Seeing people living with sickle cell disease receive gene therapy in the real world is a vision that has fueled Bluebird for more than 10 years,” said Andrew Obenshain, Bluebird’s president and CEO. “This historic moment comes nearly a century after sickle cell disease was the first genetic disorder to be characterized at the molecular level and almost a decade after Bluebird initiated clinical development for Lyfgenia. We are grateful to the patients, caregivers, researchers, and clinicians whose work made this milestone possible, and look forward to continued partnership with the sickle cell disease community.”