Bluebird Bio, Third Rock & Genzyme’s Gene Therapy Bet, Shows Promise for Blood Disorder

Genzyme and Third Rock Ventures bet $35 million six months ago on a Cambridge, MA-based gene therapy company. Despite all the ups and downs with gene therapy over the years, now we can see why they placed the bet.

The newly renamed Bluebird Bio, formerly known as Genetix Pharmaceuticals, is coming out today with an eye-opening paper in Nature. The study says Bluebird’s experimental gene therapy offered a startling benefit for the first patient enrolled in a clinical trial, designed to treat a genetic blood disorder called beta-thalassemia. The patient, in his early 20s, had been forced to live with monthly blood transfusions since the age of four, because the thalassemia made it impossible for him to produce enough hemoglobin to carry adequate oxygen through the blood.

Since getting a single shot of the gene therapy 27 months ago, the young man has been able to produce enough hemoglobin on his own to quit getting blood transfusions. That has made it possible for him to feel vigorous enough to hold down a full-time job as a cook in Paris, said Bluebird CEO Nick Leschly. An estimated 60,000 people around the world suffer from thalassemia.

“For the first time, a patient with severe beta-thalassemia is living without the need for transfusions over a sustained period of time,” said one of the study’s co-authors, Marina Cavazzana-Calvo, a professor of hematology at the University of Paris, in a statement. Leschly hasn’t spoken to the patient, but added: “The treating physician who has talked to him has said his life has been transformed.”

Gene therapy has been one of the most glamorous, and some would say overhyped fields of biotech of the past two decades. The idea is to alter viruses that carry copies of genes into cells, where they can replace missing or faulty genes at the root of certain types of disease. This technique rode a wave of scientific enthusiasm in the early 1990s, leading to the formation of more than 100 biotech companies, and to a nearly two-decade long research effort at Genzyme. Some promising anecdotal stories have emerged over the years, but there have also been some high-profile safety concerns and clinical failures. There are still no FDA-approved gene therapies on the U.S. market.

Nick Leschly

Nick Leschly

But Genzyme and Third Rock made their $35 million investment back in March based on renewed optimism. Bluebird, which has been around since the early ’90s, is planning its next moves around the treatment of beta-thalassemia and a debilitating brain disorder called adrenoleukodystrophy.

Of course, one patient in a clinical trial is only one patient, and it’s nowhere near the kind of convincing evidence that Bluebird will need to win market clearance from regulators and broad market acceptance from doctors and patients. But it’s the sort of data that will prompt Bluebird to recruit about another 10 patients to see if the experience can be replicated, setting the stage for more rigorous testing, Leschly says.

For now, scientists will dig into the details and wonder about why this might be working. The Bluebird treatment uses a genetically engineered lentivirus to deliver a copy of a gene that enables the body to produce hemoglobin, the protein that carries oxygen in red blood cells throughout the body. While many gene therapies of the past have struggled to efficiently deliver their genetic payload inside cells, Bluebird has sought a way around this by delivering the genes into cells when they aren’t even in the body.

Here’s how this is supposed to work. Patients with beta-thalassemia can potentially be cured of their condition by getting a bone marrow transplant, in which the adult blood-forming stem cells from a sibling donor are injected into the patient, Leschly says. Only about 15 to 20 percent of patients are eligible to get this kind of therapy. Bluebird’s therapy is designed to sidestep the problem of finding a genetic match. It extracts the patient’s own adult blood-forming stem cells, and exposes them in the laboratory to the gene therapy, which essentially programs the cells to start producing hemoglobin on their own. Then the blood cells get re-infused into the patient, hopefully with new ability to produce the essential protein.

That’s what the scientists saw happen. Researchers tagged the gene so that when they took blood samples from the patient, they could see that the treated cells were producing more hemoglobin after getting the experimental treatment. The scientists also saw a connection between that improvement in the blood, and the clinical improvement that enabled the patient to stop getting transfusions.

If Bluebird can repeat this kind of finding in more of the patients it enrolls, without any severe side effects popping up later, it could be an important step ahead for gene therapy. But it’s still way too early to really talk about a “breakthrough.”

“What we need to do as a company is continue to enroll more patients, and get this on an aggressive clinical/regulatory path,” Leschly says. “It sounds simple, but to execute on this is not straightforward.” But despite the necessary caveats, Leschly, who left his post as a partner at Third Rock to become Bluebird’s CEO this month, speaks with a voice filled with optimism: “I wouldn’t be here if I wasn’t pretty passionate about it,” he says.

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