Bluebird Bio has been singing the praises of two new therapies at the annual American Society of Hematology, but although the data look solid so far, investors don’t seem to be fully on board with the program.
Updated results from a trial of the company's LentiGlobin gene therapy in transfusion-dependent beta thalassemia (TDT) and the first data with anti-BCMA therapy bb21217 in multiple myeloma have both been among the highlights of the weekend schedule of the San Diego meeting. Nevertheless, shares in Bluebird have continued their steady decline of recent months, with a 6% dip premarket.
On Saturday, Bluebird reported eight of 10 TDT patients treated with LentiGlobin on the phase 1/2 NorthStar trial did not need a transfusion to prop up their hemoglobin for at least 12 months, with two patients transfusion-free for more than three and a half years. The biotech also reported data showing that excess iron levels in the liver—caused by repeated transfusions and potentially toxic—had started to decrease.
Yesterday, it also presented the first data on its Celgene-partnered anti-BCMA adoptive cell therapy bb21217, showing the CAR-T achieved an objective response in 10 of 12 (83%) heavily pretreated myeloma patients, including three patients with a complete response or stringent complete response.
Crucially, the bb21217 study also showed some evidence that the CAR-T cells were persisting in the body longer than Celgene and Bluebird’s first-generation anti-BCMA therapy bb2121, which was shown at ASCO to have a high level of efficacy but disappointed some analysts as the data suggested some tailing off of activity within a year.
Bb21217 has been specifically designed to extend the persistence of the cells in the body by selecting for more memory T cells in the production process, achieved by culturing the cells in the presence of a PI3K inhibitor.
In the CRB-402 study, three of three patients showed persistence of CAR-T cells for at least six months, which is a preliminary sign the therapy could provide “a more durable benefit for patients,” according to Bluebird’s chief medical officer David Davidson, M.D.
The data in the trial only came from the first dose of bb21217 tested, and Bluebird and Celgene now plan to double that in the next stage of the trial. They reckon the new CAR-T is working exactly as hoped, showing evidence of greater persistence than bb2121 but also not eclipsing the first-generation anti-BCMA therapy when it comes to efficacy.
So why the weighed down share price? There has been some debate about a case of myelodysplastic syndrome (MDS) observed in a patient in the LentiGlobin study, raising fears about the long-term safety of the gene therapy, although Piper Jaffray analyst Tyler Van Buren reckons that could result from the intensive conditioning regimen given during the procedure rather than the therapy itself.
That is a view also held by analysts at Jefferies, who note there is a documented risk of MDS with one of the drugs used in the conditioning process. They reckon it is still too early to compare bb21217 and bb2121, but note that “in our view, this initial response signal is very encouraging, and durability of response should be the key focus for bb21217 to be differentiated from first-gen BCMA CART.”
There is, however, a host of new BCMA-targeting therapies generating data at ASH that could pose competition to both bb2121 and bb21217. That includes drug treatments such as Amgen’s bispecific antibody AMG 420 for myeloma, for which new data are due later today, as well as rival CAR-Ts from Johnson & Johnson and Celgene/Juno.
Stellar results with AMG 420 in a phase 1 trial in heavily pretreated patients, including five out of five complete responses with four of these showing no evidence of residual disease, have led to speculation that AMG 420 could pose a real threat to CAR-Ts in myeloma. Today’s presentation will be watched with interest.