Science Driving Gene Therapy Development At bluebird bio
By Ed Miseta, Chief Editor, Clinical Leader
For patients with sickle cell anemia, just getting through the day can be a struggle. Sickle cell is a condition in which normally round and flexible red blood cells are instead rigid and sticky. The irregularly shaped cells get stuck in small blood vessels, which can slow or block the flow of blood and oxygen. Symptoms of the disease include vision problems, swelling of the hands and feet, and periodic episodes of pain that can last from a few hours to a few weeks. It can also be deadly, as most individuals diagnosed with the disease in the U.S. do not live past the age of 44. Currently there is no cure.
Nick Leschly, CEO (AKA chief bluebird) at bluebird bio, spoke at the 2018 Veeva Summit on the progress being made with its investigational gene therapy for sickle cell disease.
“Gene therapy has always shown tremendous promise,” says Leschly. “It seems we have always felt change would come in the next five years. But it has been that way for the last 35 years. But what is finally changing is the science. We are finally starting to understand, at a genetic level, what drives these diseases and how we can interact and affect them. First, we began to understand these diseases in the academic setting. Then, companies developed the needed technologies we need to manipulate cells and get them to do what we want them to do. Those two things together have now driven us to the third and final point, which is producing data that gives people reason to believe.”
The work being performed at bluebird started almost 20 years ago. The company now believes it can remove blood stem cells from the bone marrow of a patient. The cells are put in a bag and a virus is introduced that will go inside the stem cells and insert a piece of DNA. That DNA knows how to code for a functioning blood cell. The cells are then reinjected into the arm of the patient. They go back into the bone marrow and the goal is that the cells will produce functioning copies of red blood cells.
“This process provides patients with a manufacturing plant in their bone marrow that will produce functioning copies of hemoglobin,” states Leschly. “We have done this several times, and results were just published in the New England Journal and we are well on our way to proving this effect in clinical studies. Our hope is that patients suffering from this disease may soon have a fundamental shift in their quality of life.”
Science Fiction Comes to Life
This process sounds a bit like science fiction, and years ago that’s actually what it was. A dream that resided in the minds of scientists. But gene therapy technology has made huge advances and now has bluebird on the threshold of making this a reality.
The treatment is obviously highly personalized, and it can take weeks, if not months. There are also challenges that still need to be overcome. The number one challenge is figuring out how to acquire the right cells. When the cells are put in the bag, a process called transduction is performed. This involves getting the virus into as many cells as possible and fixing them. Finally, those cells need to get back to where they can do the most good for the body.
“All of this sounds incredibly difficult, but I also look at it as a FedEx problem,” says Leschly. “We have to figure out how to move the cells around and have them keep all of their properties that we want them to have while introducing the properties they need to have. We have come a long way towards making that happen. But now we also face a logistical challenge. The cost to produce this type of gene therapy is huge. But I also believe it is a solvable problem. If we have something that people believe in, and that will save lives, then we can figure out a way to make it work.”
One barrier that Leschly does not believe will stand in the way of a treatment is the regulatory agencies. He believes the FDA, EMA, and other regulatory bodies want to get needed products to patients. However, he notes these agencies are not willing to take a leap of faith. Sponsor companies will have to go to them with proven science and supporting data. What pharma companies are proposing must make sense. Leschly refers to this as rule number one.
These treatments are very complicated, but Leschly states the regulators know and understand that. Regulators have been engaging with companies searching for complicated treatments, and he notes they have been collegial with members of the gene therapy community. FDA commissioner Scott Gottlieb has been an instrumental part of moving gene therapies forward, and has let sponsor companies know the FDA is willing to work with them to get needed therapies to patients.
“We are not just talking about sickle cell,” states Leschly. “We are talking about cancer and many other diseases as well. There is a lot at stake and the regulatory agencies know that. They have been communicating and engaging with us, and even asking how they can best work with sponsor companies. We really are building this plane as we fly it and continue to struggle with how to perform these studies safely and effectively, and how to best balance risk and benefit.”
Pricing Takes A Village
If the efforts of bluebird in sickle cell are successful and lead to an FDA approval, it will have to price its life-saving treatment. Pricing has been an issue in pharma for years, and in some instances the industry has gotten itself in trouble with those decisions. As the industry continues to get approval of life-saving cell and gene therapies, pricing issues will continue to surface. Cell and gene therapies are not medicines that patients will take over extended periods. They are a one-time treatment of a lethal disease, which can make pricing an even greater challenge.
Leschly believes we could spend days discussing pricing. However, he stresses pricing of these new treatments is a great opportunity for sponsors and for that reason they need to make sure they do it the right way. Some in the industry will say new treatments are costly, take a long time to develop, and involve taking on a lot of risk. Those factors then justify the high cost. Leschly says that is not the approach that will be taken by bluebird bio.
“Our goal is to do what is right for all stakeholders, including patients, payers, and public and private institutions,” says Leschly. “For this type of treatment, we have to take a multi-disciplinary approach. There must be a value-based payment over time. Although that is remarkably simple to say, it's incredibly complicated to execute.”
Leschly believes there is a best price for this type of treatment. Since this is a treatment for life, which requires a payment over time, it should not matter if the recipient moves or changes payers. He believes pricing issues are solvable, even if they require legislation. Sixty percent of patients with sickle cell are on Medicaid. That is one payer which can simplify the equation. Still, regardless of who is paying for the treatment, the pricing solution must be reasonable and consider all stakeholders.
“That is what we are doing right now,” says Leschly. “We are talking to payers at all levels and being open to the fact that we need to do this in a transformative way. We cannot price the way we have in the past. You cannot charge patients a certain price simply because you can. I don't want to go home and tell my daughters that's what bluebird is doing.”