reduce if not eliminate the need for transfusions. One is a gene therapy, from Bluebird Bio (NASDAQ: [[ticker:BLUE]]). A single infusion of the treatment, called LentiGlobin, is meant to restart hemoglobin production for life, the same effect as a bone marrow transplant but without the fear of a deadly rejection of the donor’s blood. (That said, the LentiGlobin procedure still requires a chemotherapy step called myeloablative conditioning that carries certain risks, as well.)
European regulators have begun a review that could lead to approval next year; Bluebird has not yet asked the FDA to begin a review.
Luspatercept, from Acceleron and Celgene, is also meant to boost hemoglobin but requires an infusion every few weeks. Acceleron could ask for approval of the drug in both the U.S. and Europe next year.
Both therapies have limitations. Patients are excited about living a “normal life” with the help of a gene therapy, says Butler, but it’s unclear who will be eligible and how long the improvement will last. Bluebird has reported different results in different genetic subsets, and patients want “clarification whether [LentiGlobin] would theoretically work for all types of beta-thalassemia major, or whether it will have limited efficacy only for certain types,” Butler says.
It’s also unclear how insurers will deal with the variations, and what they will do if patients switch insurers. Butler also notes that the myeloablative conditioning that precedes the gene therapy might scare off patients, as well.
Butler says that luspatercept could appeal to patients who see gene therapy as too risky. Like LentiGlobin, however, it’s unclear which patients might benefit. Acceleron and Celgene reported in July that luspatercept provided at least a 33 percent reduction in the volume of blood transfusions after 13 to 24 weeks of treatment. An ASH abstract posted in November showed that 21.4 percent of luspatercept patients achieved this response, compared to 4.5 percent of placebo patients. But more details are necessary to answer big questions, and Acceleron is expected to provide them at ASH.
At ASH, Bluebird will address the durability question with data from patients who received LentiGlobin as much as 3.5 years ago, in an early study dubbed Northstar. Bluebird will also update results from a Phase 3 study called Northstar-3 to include data from a key genetic subset of patients who so far have had the toughest time responding to its treatment. That study will help form the basis of Bluebird’s approval application in the U.S.
Elsewhere, LJPC-401 from La Jolla Pharmaceutical (NASDAQ: [[ticker:LJPC]]) is in early testing and will get an ASH update. It’s a synthetic form of the hormone hepcidin, which helps the body regulate iron absorption and may prevent build-up. If, someday, both a hemoglobin booster and hepcidin were available for beta-thalassemia patients, “the combination of the two could make a really big difference,” Butler says.
SICKLE CELL DISEASE
Long bereft of pharmaceutical options, patients with sickle cell disease are well aware that several new experimental therapies are in development. Some promise long-lasting relief with a single treatment (it’s premature to use the word “cure”); some are meant to better manage the severe pain, anemia, and other debilitating symptoms of the inherited disease.
Sickle cell’s hallmark is abnormal crescent-shaped red blood cells that clog blood vessels and block the flow of oxygen. As with beta-thalassemia, the disease stems from a mutation in hemoglobin. Only two drugs have been approved to treat the symptoms: a repurposed chemotherapy and a version of a dietary supplement. Beyond those medicines, there are blood transfusions and plans, like helping patients avoid emergency room visits, to improve lives. Those efforts will be a big part of the sickle cell story at ASH this year.
For example, researchers will discuss a large study called ESCAPED, which shows that treating people with pain episodes (or “crises”) in infusion centers instead of in emergency rooms, where they often end up, controls their pain faster and improves care significantly, with a six-fold decrease in costly hospitalizations.
Is “cure” an appropriate description for gene-altering medicines? We don’t know yet, and ASH won’t help us divine much. Bluebird’s gene therapy LentiGlobin has been working its way through early testing for sickle cell, and the company has been tweaking the parameters of a Phase 1 trial; investigators will share an early look at a third group of patients.
Another avenue of sickle-cell gene therapy aims to switch off the faulty adult hemoglobin and revert the patient back to the healthy fetal version of hemoglobin. Bluebird’s program will get an extremely early airing at ASH.
(A sickle cell treatment that uses CRISPR-Cas9 gene editing—the first human study of its kind—is about to start any day now. Perhaps it will be one of the must-see presentations at next year’s ASH.)
For all the hope of fixing genes, sickle cell disease does in fact have a cure. But the treatment, bone marrow transplant, is rarely an option for African-Americans, who make up the majority of the roughly 100,000 U.S. patients. A gene therapy, if eventually approved, could widen that door.
That said, a paper to be presented at ASH looks back at nearly two decades of transplants for pediatric sickle cell patients in Europe. The success rate—two years of survival—was mostly in the 82 percent to 96 percent range, depending on the donor. (Best success: perfectly matched siblings.) The study authors conclude that new, expensive medicines will have a high bar to clear: “The emerging gene therapy approach will have to be compared to these well-established results.”
The most advanced new experimental drug to get an airing at ASH is
