Around this time last year, when the FDA put a partial clinical hold on bluebird bio's sickle cell disease (SCD) lovo-cel for patients under the age of 18, it raised questions about the regulatory timeline of the gene therapy.
But 12 months removed from the scare—and after continued observation of lovo-cel recipients—the Massachusetts-based company says it is still on track to submit its biologics license application in the first quarter of next year, chief medical officer Rich Colvin, M.D., Ph.D., said in an interview ahead of the company’s presentation Saturday at the American Society of Hematology annual conference in New Orleans.
Red flags popped up about LentiGlobin—which includes lovo-cel’s sister therapy Zynteglo—as two of 32 patients in Group C of a phase 1/2 study had anemia after their infusions, creating concern that the treatment could lead to myelodysplastic syndrome (MDS). But the two patients—one adult and one pediatric—have remained clear of the cancer type.
“We’ve looked deep,” Colvin said. “None of the data are indicative of an emerging malignancy.”
The older anemic patient was the only one in the overall study who had a severe vaso-occulive event through 24 months of follow-up and remains transfusion dependent. The younger anemic patient has not required transfusions.
The common thread between the two patients was that they were the only ones in the study with two alpha-globin deletions. The company concluded in its abstract that the trait may contribute to anemia and dyserythropoiesis—which is the defective development of red blood cells—in lovo-cel recipients.
“The bottom line is both of these patients have the alpha-thalassemia trait, and because of that they started out being anemic and they continue to be anemic after therapy,” said Colvin, who added that approximately 4% of those with SCD have the a-globin characteristic.
Zynteglo patients show improved quality-of-life
At ASH, bluebird also presented data from two abstracts on its other LentiGlobin therapy, Zynteglo (beti-cel), which was approved by the FDA in August of this year. The gene therapy, which treats beta thalassemia, has been administered to 63 patients spanning the last eight years.
Of the 41 participants in two phase 3 studies, 37 (90%) have achieved transfusion independence, accompanied by significant quality-of-life improvements.
Based on testimonials collected three years after treatment, 93% were able to work, compared to 67% at baseline. There also was a reduction in school absences from 95% at baseline to 50% after three years. In addition, 81% of recipients reported an improvement in physical activity, while 100% said they had an overall improvement from treatment.
“It’s easy to measure their hemoglobin levels. It’s easy to show that they didn’t need any more transfusions,” Colvin said. “But when they actually report it and they say it—considering they had such a high baseline of feeling great in their own mind—I think this is a very big finding.”