Bluebird adjusts to a new reality with its much-scrutinized gene therapy

bluebird CEO Nick Leschly

Bluebird bio ($BLUE), at work on a promising gene therapy for a rare blood disease, has shifted its clinical strategy after learning that its treatment doesn't work the same way for all patients with the disorder, planning to split up the population in future studies.

The company, presenting incrementally encouraging data at the weekend's American Society of Hematology meeting, said the future development of its LentiGlobin BB305 would recognize a key difference in patients with the rare beta-thalassemia major. But investors have found the lack of a major response among some patients a disturbing indication of the limitations of Bluebird's therapies, clouding its future and driving the biotech's shares down 33% in pre-market trading on Monday.

The disorder results from a defective beta-globin gene that stops patients from producing the hemoglobin they need, often leading to severe anemia. But within the beta-thalassemia population are two key patient groups: those who can manufacture trace amounts of beta-globin and those who are completely incapable. Last month, bluebird's share price tumbled after it disclosed that BB305 had a weaker effect on the latter group, failing to wean them off of the need for blood transfusions after 6 to 18 months.

Now, adjusting to that revelation, bluebird is planning to stratify its future studies. The biotech is sticking to its plan to enroll two more studies on BB305 but now plans to target only patients with the less severe form of beta-thalassemia. In addition, bluebird is planning to start a third study enrolling only patients who produce no beta-globin.

Bluebird traded as high as $194 a share in the spring, at the height of biotech's current boom, when BB305 looked like a cure in the making for beta-thalassemia and shareholders cheered tantalizing early data suggesting it could have a similar effect on severe sickle cell disease. The company's share value has since come clattering back to earth, down more than 55% since then as a more complicated picture of BB305 has come into view.

Meanwhile, at ASH this weekend, bluebird presented some upbeat results from the ongoing studies it discussed last month. In a trial on 9 patients with beta-thalassemia, the 5 with semi-functional beta-globin genes have remained free of transfusions for between 7.1 to 16.4 months, the company said. The four with the genetic variant still require new blood to survive, but BB305 has resulted in a reduction of transfusion volume of between 33% and 100%, bluebird said.

In results from a separate study presented Sunday, two beta-thalassemia patients remain transfusion-free after 21 and 18 months, and bluebird has treated two more but must wait a few months before drawing any efficacy conclusions.

Bluebird is also working through a pair of studies testing BB305 in sickle cell disease, dosing four patients with the gene therapy so far with mixed early results.

The first patient has remained free of transfusions for 9 months, bluebird said, and his levels of anti-sickling hemoglobin have risen to levels the company believes demonstrate a sure sign of clinical efficacy. But for two patients infused with BB305 more recently, things aren't progressing so quickly. Each reported anti-sickling hemoglobin levels of only around 17% at least three months after infusion, a gradual increase from baseline that falls short of the positive results seen in the first patient.

Bluebird is preaching patience, saying it will need to see longer term data and more subjects before making any conclusions about BB305's potential in sickle cell.