New Data Show Power, Limits of Bluebird’s Gene Therapy For Blood Diseases

Xconomy Boston — 

Bluebird Bio is releasing new data this morning that speak to both the potential and the limitations of a gene therapy it’s been developing for two deadly blood diseases, sickle cell disease and beta-thalassemia.

The data, from abstracts for presentations that will be given at the annual meeting of the American Society of Hematology in San Diego next month, show that Bluebird’s (NASDAQ: BLUE) LentiGlobin gene therapy might be a long-lasting, effective treatment for some patients with these diseases. But they also show why Cambridge, MA-based Bluebird has recently upgraded its technology—some patients, primarily those with sickle cell, haven’t responded as well as others to the earlier version used in the trials. Bluebird will release more details from these trials at the December meeting.

In total, Bluebird is reporting on 30 patients from three different studies: 18 from a study (named Northstar) of patients with beta-thalassemia, five from a study of patients with either beta-thalassemia or sickle cell (named HGB-205), and seven from a study only of sickle cell patients (HGB-206).

In beta-thalassemia, the story remains very much the same for Bluebird as in previous releases of data from the studies. Patients with two copies of a type of genetic mutation called b0 don’t respond as well as those without those mutations. And those without two b0 mutations have seen durable responses that have freed them—in some cases for a few years now—from the blood transfusions that they normally require to prevent severe anemia.

The five beta-thalassemia patients in the Northstar study without two copies of the b0 mutation and at least 12 months of follow-up are free of transfusions and have been for a median of 19.4 months. Similarly, the four beta-thalassemia patients in the HGB-205 study, all without two copies of the b0 mutation, are also transfusion free, and two of them have been for 31 and 28 months respectively.

The eight patients in the studies with two copies of the b0 mutation, meanwhile, have had the volume of their transfusions reduced by about 60 percent, but aren’t free of them. About 288,000 people worldwide have beta-thalassemia, and an estimated 60 to 80 percent of them have the most dire form, known as beta-thalassemia major. Roughly one third of those patients have two copies of the b0 mutation.

In sickle cell disease, Bluebird has now treated eight total patients, and seven of them haven’t responded nearly as well as the first volunteer the company treated. Sickle cell occurs when a defective gene causes the bone marrow to produce abnormal crescent or sickle-shaped red blood cells. These cells don’t move freely through the bloodstream like normal red blood cells do; they’re stiff and liable to get stuck and block blood flow, causing anemia, organ damage, and chronic pain that can last for weeks or months at a time.

That first sickle cell patient on LentiGlobin was treated in October 2014, hasn’t needed transfusions since three months after the treatment, and hasn’t been hospitalized for any sickle cell-related complications since. After 18 months of treatment, more than half the hemoglobin the patient is producing (6.6 grams per decileter (g/dL) of blood) is the anti-sickling form that results from the Bluebird treatment. Bluebird believes, based on historical data, that if patients can produce about 3 g/dL of anti-sickling hemoglobin it might be enough to alter the course of their disease.

The other seven patients, all from study HGB-206 and treated anywhere from three months to a year ago, haven’t had the same type of response. Those patients produced a median of just 0.4 g/dL of therapeutic hemoglobin after three months of treatment. The abstract says that most patients then had “modest increases” over time, and the best responder has 1.2 g/dL of therapeutic hemoglobin after 12 months. But these responses don’t yet meet the bar Bluebird needs to hit consistently for LentiGlobin to be an effective, long-lasting sickle cell treatment.

Bluebird has changed up the manufacturing process for LentiGlobin to try to make the therapy more effective and overcome the variation in responses that it’s seen so far in both sickle cell and beta-thalassemia patients. None of the data to be presented at ASH incorporate those changes, so it’s unclear at this point how much of a difference they’ll make. But the proof will come next year: Bluebird will use the upgrades both in its existing trials for beta-thalassemia and sickle cell disease, and the new ones it’ll run going forward. That data will go a long way towards showing how broadly effective LentiGlobin can be.

Check out these stories for more on Bluebird, LentiGlobin, and gene therapy.