Life-Shortening Blood Disease Gets Rush of Research

(Bloomberg) -- More than 50 years after the cause of sickle-cell disease was discovered, a dozen treatments for the painful and life-shortening inherited condition offer hope for long-overlooked patients.

The disorder, which requires frequent blood transfusions and kills most patients in their 40s, got its name from round shaped red blood cells that get malformed into sickle-shaped ones. The condition has been neglected for years and affects mainly minorities in the U.S. -- where there are 100,000 patients -- and populations in Africa and Asia.

Now it’s getting the attention of cutting-edge researchers. Bluebird Bio Inc. hopes to cure patients with a single injection of its gene therapy one day. Farther down the road are even more potent and permanent experiments using the gene-editing technology Crispr, an approach that hasn’t been done in humans yet.

“Sickle cell disease has been incredibly left behind in medicine,” said Julie Kanter, director of sickle cell research at the Medical University of South Carolina. “We desperately need more disease-modifying therapies and there is room for all of these.”

Bluebird’s LentiGlobin gene therapy and the promise of Crispr were in the limelight at the American Society of Hematology, or ASH, meeting in Atlanta this weekend, capturing the imagination of what could done to cure diseases caused by defective genes. Coming sooner will be more conventional therapies to treat symptoms, like Global Blood Therapeutics Inc.’s voxelotor, one of the first drugs designed specifically for sickle-cell disease.

Voxelotor, a pill taken five times a day, reduced anemia and pain in a trial of 11 teenagers presented at ASH. And Novartis AG’s crizanlizumab, an antibody infused in the body, also delayed the onset of pain.

The excitement about gene therapy sent Bluebird, one of the stars at ASH, soaring on Monday. The stock jumped as much as 30 percent to a record $222.03 after the Cambridge, Massachusetts-based drugmaker released updates from several trials, including on a therapy for blood cancer.

Global Blood dropped 3.6 percent. Data presented at ASH included the death of two severely ill patients, age 66 and 44. Their death was unrelated to the drug, trial investigators said.

Sickle-cell disease produces misshapen oxygen-carrying hemoglobin, causing severe pain as well as damage to the organs, vessels and joints. The primary treatment today is hydroxyurea, a generic drug. Researchers believe it works by stimulating production of fetal hemoglobin, a form of the protein produced in the womb that doesn’t have the damaging characteristics of the malformed “sickled” adult protein.

When Emmaus Life Sciences Inc. received U.S. approval of its powder Endari in July to reduce severe complications, it was the first new medicine for the disease in 20 years and the second ever cleared by the Food and Drug Administration.

Historically Overlooked

About 80 percent of Americans with the condition have government-based insurance such as Medicare or Medicaid, one reason the market has been historically overlooked, said Liz Klings, director of the Center for Excellence in Sickle Cell Disease at Boston Medical Center. As government financial incentives focused on rare diseases emerged in recent years, there has been unprecedented interest from drugmakers, she said.

At the medical meeting in Atlanta, Bluebird reported data on the first person to receive LentiGlobin after a change in the manufacturing process. At comparable time periods, that patient is doing better than the person known as the French patient, who was the first person to get the therapy and had responded well.

The new patient, not previously a runner, took up the hobby and is now at about three miles a day, said Kanter, from the Medical University of South Carolina, who presented the results.

Another tweak allowing Bluebird to extract cells from blood instead of bone marrow also is looking promising. The first person to receive that approach, which is faster and easier for patients, started producing engineered hemoglobin, said Dave Davidson, Bluebird’s chief medical officer.

Next Step

The next step could be treatments using Crispr, which permanently changes the DNA of the hemoglobin cell, while gene therapy makes an improved version of the gene that may or may not be accepted by the patient’s system. Swiss biotech Crispr Therapeutics AG plans to file to begin studies in the U.S. next year. Novartis, a global pharmaceuticals giant, has also plans to begin trials shortly.

A product could be on the market within five years, said Sam Kulkarni, chief executive of Crispr Therapeutics.

“With the kind of benefit you can potentially get from a therapy like this, I think the regulators will be OK with accelerated trials,” Kulkarni said. “If the data bears out like we expect it to and there is a huge benefit, we can expand quickly.”

Crispr, like Bluebird’s LentiGlobin, won’t be a magic bullet. The process is complicated and the novel therapies will be costly. If they work as expected, patients could be cured, but they would still carry the original gene and could pass it along to their children.

In the meantime, drugs like Global Blood’s voxelotor will offer a more affordable relief for patients. Voxelotor binds to hemoglobin and holds on tightly to oxygen, preventing about 30 percent of the cells from forming a sickle shape and becoming sticky.

“The curative options are exciting, but they won’t be available to a majority of patients for a long time,” said Carolyn Hoppe, associate hematologist from University of California San Francisco’s Benioff Children’s Hospital in Oakland, and lead researcher on the voxelotor trial. “People are focusing on getting a cocktail of drugs that can be given safely that work differently until we can get to the point of cure.”

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net.

To contact the editors responsible for this story: Drew Armstrong at darmstrong17@bloomberg.net, Cecile Daurat

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