With Upgraded Tech, Bluebird Updates Regulatory Path For Gene Therapy

Xconomy Boston — 

After flying high for a few years, Bluebird Bio has dealt with some adversity. Limitations emerged late last year for a gene therapy the company was developing for the blood diseases beta-thalassemia and sickle cell disease, and shares took a beating. Ever since then, the Cambridge, MA, company has been working to improve its technology.

Those modifications, now finished, are being incorporated into Bluebird’s clinical development plan. Now it has to show that they’ll lead to better outcomes.

In May 2015, Bluebird (NASDAQ: BLUE) said it had come to an agreement with regulators in the U.S. and Europe on an approval path for LentiGlobin, which has a chance to be among the first approved gene therapies in the world. (Two others are already approved in Europe, and the first U.S. approval could come for Spark Therapeutics next year.) At the time, Bluebird had said that it would have to run two 15-patient, open-label studies called HGB-207 and HGB-208 in addition to the other trials it had already started to win FDA approval. The goal was to track these patients’ results for two years, and hopefully free them from the blood transfusions that beta-thalassemia patients normally require to prevent anemia for at least 12 months.

LentiGlobin produced stunning early results in beta-thalassemia and became a shining example of the renaissance gene therapy has undergone over the past few years. In a handful of patients, Bluebird had a 100 percent success rate in freeing people from transfusions. Last November, however, limitations emerged. Patients with the most severe form of beta-thalassemia, with two copies of a type of genetic mutation called b0 didn’t respond as well. Similarly, three patients with sickle cell disease didn’t respond as well as the first volunteer Bluebird had treated with LentiGlobin. As a result, Bluebird’s shares took a hit. They’re currently worth about $65 apiece, which, while almost four times its $17 IPO price, is about a third of its 2015 highs of more than $194 a share.

Since late last year, Bluebird has been changing up the manufacturing process for LentiGlobin in an effort to make it more effective in both sickle cell and beta-thalassemia patients, hoping to overcome the variability of results it’s seen so far. It’s now finished those modifications.

Investors had been concerned that Bluebird might have to start all over again in clinical trials if it were to incorporate the manufacturing improvements, but the company reported recently that that isn’t the case. 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.

Additionally, the company today provided a little more clarity on its path to potential approval should LentiGlobin perform well in additional testing. To win FDA approval, Bluebird will still need two additional studies in the U.S., but they’re a bit different than the ones the company outlined before. HGB-207 (also named Northstar-2), will now no longer include patients with two b0 mutations. It’ll also include two study groups: the first will consist of 15 adult and adolescent beta-thalassemia patients, and the second will consist of eight children with the disease. The second study, named HGB-212, will have 15 adult, adolescent, and child patients with two b0 mutations. That study will start in 2017, and Bluebird will have to show an ability to reduce the frequency of transfusions. (HGB-207 is already underway.)

Bluebird also says it has gotten confirmation that it can apply for conditional approval of LentiGlobin in Europe based on the data from two ongoing studies, HGB-205 and Northstar, and available data from the two additional trials, HGB-207 and HGB-212.

Bluebird has also expanded the study it’s running in sickle cell patients, which will now include up to 29 patients.

The company will host a conference call this morning to discuss the news and the rest of its clinical and regulatory strategy.