Most patients are free from VOEs after gene therapy treatment

Therapy was approved by FDA this month for people with SCD, 12 and up

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Most sickle cell disease (SCD) patients treated with the gene therapy Lyfgenia (lovotibeglogene autotemcel) in clinical trials were free from vaso-occlusive events (VOEs) after a median of three years of follow-up.

That’s according to new data from Lyfgenia’s developer, Bluebird Bio, at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition. Also known as lovo-cel, Lyfgenia was last week approved by the U.S. Food and Drug Administration (FDA) to treat SCD patients ages 12 and older with a history of vase-occlusive events (VOEs).

“Years of long-term follow-up continue to suggest that lovo-cel has potential to address the underlying cause of sickle cell disease and provide robust clinical benefits for patients. The data presented at ASH give us confidence that these results can be sustained over time and may translate to meaningful and lasting impact on quality of life for people living with sickle cell disease who need and deserve new treatment options,” Richard Colvin, MD, PhD, Bluebird’s chief medical officer, said in a company press release.

SCD is caused by mutations in the gene HBB, which provides instructions for making part of hemoglobin, the protein used by red blood cells to carry oxygen through the bloodstream. SCD-causing mutations lead to an abnormal form of hemoglobin being produced that forms clumps in blood cells, deforming their shape and making it harder for them to flow through blood vessels. This can can set the stage for VOEs — which include painful vaso-occlusive crises (VOCs), acute chest syndrome, and other complications — as well as other SCD symptoms.

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Gene therapy lowers number of red blood cells that take sickle shape

Outcomes of Lyfgenia treatment

Lyfgenia delivers a version of the HBB gene that encodes a clumping-resistant form of hemoglobin. In the treatment, a patient’s blood stem cells are collected from bone marrow, engineered to carry the therapeutic gene, then replaced through a stem cell transplant.

“This one-time, transformative therapy has the potential to target the underlying cause of the disease and reduce both pain and fatigue — outcomes that matter to people living with sickle cell disease and their families,” said Julie Kanter, MD, an investigator on the clinical trials at the University of Alabama Birmingham.

The new ASH data covered 47 patients who received the therapy as part of the Phase 1/2 clinical trial HGB-206 (NCT02140554) or the Phase 3 trial HGB-210 (NCT04293185). All were treated with a version of Lyfgenia made using enhancements to the treatment process and manufacturing protocols.

Among the 47 patients, 34 were evaluable for VOEs over a median follow-up time of roughly three years. Some have been followed more than five years since being treated.

Of the 34 evaluable individuals, 30 or 88.2% were free from VOEs that required medical care during the follow-up. Only two patients had serious VOEs that required more than a day in a hospital. All 10 adolescents evaluated were free from VOEs during the studied period.

For the eight trial participants who have had any documented VOEs in the trial, the rate of VOEs decreased by at least 50% compared to the rate before Lyfgenia treatment for all of them. Among these patients, the median time spent in a hospital decreased from more than two weeks a year before treatment to about two days a year after gene therapy.

Other gains with gene therapy treatment

Measures of quality of life, including assessments of fatigue and pain, showed significant improvements as soon as six months after treatment and these gains were maintained after three or four years of follow-up.

“These new data provide further evidence that lovo-cel can provide significant improvements in quality of life for people living with sickle cell disease and that the effects are durable for at least five years,” Kanter said.

After treatment, the anti-clumping form of hemoglobin accounted for more than 40% of all the hemoglobin in blood cells for most trial participants, biomarker data indicated. Most markers of blood cell health were near normal ranges after treatment.

“We see meaningful changes in hemoglobin, excellent production of anti-sickling hemoglobin, and improvement in all markers of hemolysis, which further reinforces the clinical effects of lovo-cel,” said Kanter said, adding the findings “support the positive impact of lovo-cel on the biology of sickle cell disease and on patients’ clinical outcomes and quality of life.”

Data from the 47 patients indicated the treatment was generally well tolerated. Two patients had serious side effects related to treatment, including two instances of severe anemia and one of myelodysplastic syndrome, a type of cancer marked by the abnormal growth of blood stem cells.