Bluebird Bio said Tuesday that it has suspended clinical trials involving its gene therapy for sickle cell disease after receiving reports that two patients treated with the one-time therapy were diagnosed with cancer.
The trials were placed on “temporary suspension” so that Bluebird can investigate the cancer cases to determine if they were caused by the re-engineered HIV virus used to deliver its gene therapy. No such link has been established yet, the company said.
In December 2018, Bluebird disclosed the diagnosis of myelodysplastic syndrome (MDS), a cancer-like disease of the bone marrow, in a sickle cell disease patient who had undergone treatment with its Lentiglobin gene therapy three years beforehand. At that time, Bluebird concluded that the chemotherapy administered to the patient to prepare for the gene therapy was likely the cause of the cancer, based on tests it conducted. The patient subsequently died last July.
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The new cancer cases, however, will refocus attention on a possible cancer risk inherent with Bluebird’s gene therapy — and also raise concerns for any gene therapy company that uses re-engineered lentiviruses as part of its treatments.
Shares of Bluebird fell 32% to $31 in Tuesday trading — its lowest price in seven years.
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Bluebird said it received a report last week that a patient with sickle cell disease treated more than five years with its Lentiglobin gene therapy had been diagnosed with acute myeloid leukemia.
Also last week, Bluebird said it learned that a second patient with sickle cell disease, also treated with Lentiglobin, had been diagnosed with myelodysplastic syndrome.
“The safety of every patient who has participated in our studies or is treated with our gene therapies is the utmost priority for us,” Bluebird CEO Nick Leschly said in a statement. “We are committed to fully assessing these cases in partnership with the healthcare providers supporting our clinical studies and appropriate regulatory agencies. Our thoughts are with these patients and their families during this time.”
The Food and Drug Administration and the European Medicines Agency have both been informed about the cancer cases and the suspension of the clinical trials, Bluebird said. The investigation of the cancer cases will seek to determine if the Lentiglobin gene therapy could have caused the patients’ cancer, by possibly inserting the modified stem cells in the wrong place. This is a theoretical risk for any gene therapy that uses viruses as a delivery vehicle, but had not yet materialized in clinical trials until Bluebird’s reports.
Before patients can be treated with gene therapy for sickle cell disease, or other blood-related illnesses, they must first be administered a chemotherapy called busulfan, which clears out — or “conditions” — the bone marrow so that it can accept the healthy cells delivered by the gene therapy.
Cases of MDS have been previously reported in patients undergoing stem cell transplant conditioning with busulfan. Clinical trials are currently underway seeking to develop more effective and safer ways to prepare patients for gene therapy. The research is important because even if gene therapies for sickle cell disease or related genetic diseases are approved, patients may be reluctant to try them for fear that the cure could also place them at an increased risk for later developing cancer.
There have been no cases of AML or MDS reported in patients with beta-thalassemia treated with Zynteglo, the Bluebird gene therapy approved in Europe that is made similarly to Lentiglobin. However, the company has temporarily suspended the marketing of Zynteglo while the investigation into the cancer cases is underway.
