Bluebird Bio Looks to Move Past Hot Papers, Charge Ahead in Clinic With Gene Therapy

Xconomy Boston — 

[Correction: 10:22 am 5/24/11] Bluebird Bio is one of those fortunate companies that can say the top peer-reviewed journals in biomedical research—Science and Nature—have run articles featuring its two lead drug candidates while they are still at the earliest phase of development.

CEO Nick Leschly doesn’t want to sound ungrateful—the buzz doesn’t hurt—but he seems like he’s had enough already.

“We can all go crazy, and write publications and talk about it all we want, but let’s enroll more patients and continue to prove it,” Leschly says.

Cambridge, MA-based Bluebird Bio (formerly Genetix Pharmaceuticals) has raised $65 million in the last 14 months to support its programs for gene therapy, so there are some pretty high expectations that it’s going to have to deliver on at some point. I caught up with Leschly for a quick update while he was in Seattle on Friday for the American Society of Gene and Cell Therapy conference. He said he’s focused on pushing hard and fast on things that matter less to the basic scientists and more to the folks who oversee clinical trials at the FDA.

Here are the highlights of the two programs we discussed:

—Beta-Thalassemia. This is a genetic blood disorder that makes people unable to produce enough hemoglobin to carry oxygen through the bloodstream so that they can live active lives. People can be cured with a bone marrow transplant today, but not all patients are eligible, and there can be dangerous complications with the approach.

The Bluebird treatment is designed to circumvent those issues with a different approach. It extracts a patient’s blood-forming adult stem cells and exposes them in the laboratory to the gene therapy. Bluebird uses a genetically engineered lentivirus to deliver a copy of a gene that essentially programs the cells to start producing hemoglobin on their own. Then the properly functioning blood cells get re-infused into the patient.

Nick Leschly

Last September, Nature published an article about how this approach worked for the first patient who enrolled in a clinical trial. The patient, a young man in Paris who goes by the initial PLB, was soon able to produce enough hemoglobin on his own to quit getting blood transfusions that he had depended on since the age of four.

[Corrected, with updated time frame] Three years later, the young man is still living without the need for transfusions, and no adverse events have popped up to dampen the enthusiasm, Leschly says. “No news on him is good news,” he says.

The bigger issue is that since this is gene therapy, and there have been safety concerns with other approaches in the past, doctors and regulators are inclined to tread carefully. So far, so good, Leschly says—Bluebird expects to finish enrolling all 10 patients it wants to recruit at a single location in France over the next 12 months. Lots of gene therapy watchers will eagerly watch to see if the experience of the first patient can be reproduced in that larger group.

—The other key program at Bluebird is a treatment for childhood cerebral adrenoleukodystrophy, a genetic brain disorder. This program was written up in Science, and honored as one of the top 10 breakthroughs of 2009, after two boys had their condition stabilize following Bluebird’s gene therapy.

The first two patients are still doing well, Leschly says. Now Bluebird’s plan is to move aggressively ahead to confirm the result in a bigger clinical trial. The plan is to seek FDA clearance this year to initiate a company-sponsored, global trial, enroll patients in 2012, and talk with regulators about whether this trial will provide enough evidence to seek approval to begin marketing the therapy, Leschly says.

“We feel that based on the need, and based on the proof of concept that’s already been established in a Phase 1/2 trial, this new data can move us toward the accelerated approval process,” Leschly says. The goal will be to show the gene therapy approach is as effective as a bone marrow transplant for these patients, but without the complications (finding a genetic match, dealing with immune-system reactions) inherent with that process.

Bluebird is now working to make a better lentiviral vector, combined with a better manufacturing process, to take the treatment forward in clinical trials, Leschly says.

Naturally, I had to ask if changing the vector of this therapy means Bluebird will have to start over in clinical trials. That’s not the case, Leschly says, because the company isn’t changing the “heart” of the vector. The company is using some newer lentiviral manufacturing technology that should be more efficient at delivering the genes into cells, and make the treatment easier to manufacture, he says.

Wrestling with questions like this are a sign, Leschly says, of gene therapy starting to grow up. It’s time to move ahead more aggressively in larger clinical trials, and against multiple diseases, to see if gene therapy can finally get over the hump and create marketed products that help patients.

“There’s been a lot of scientific debate, and a few disasters,” Leschly says. “There’s been clinical data, but it hasn’t been particularly good. Now you’re seeing dramatic improvements in the safety of the vectors, dramatic improvement in the data in multiple diseases. That’s an exciting thing to hear.”

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4 responses to “Bluebird Bio Looks to Move Past Hot Papers, Charge Ahead in Clinic With Gene Therapy”

  1. Ann says:

    Can you please contact me regarding a family member with adrenoleukodystrophy and if there is any possibility of helping him.



    Dear gentlemen/ladies,
    My name is Faye Anastasopoulou and i come from Greece.
    me and my sister are patients of Beta Thalassemia and we re under transfussions since early childhood.
    i m reading your articles with much respect and interest as you may imagine.
    i d like to have the e mail of mr Nick Leschly if it s possible,so to ask him about details regarding the gene therapy in beta thalassemia.
    your response would be to me and the other patients more than appreciated.

    Faye Anastasopoulou