A one-time, long-lasting treatment for the genetic blood disease beta thalassemia looks to be the next gene therapy on its way to market—at least, for now, in Europe.
The Committee for Medicinal Products for Human Use, which guides drug approval decisions in Europe, has recommended a “conditional” approval—on a thinner body of evidence than normal—of Zynteglo (formerly LentiGlobin), a gene therapy developed by Cambridge, MA-based Bluebird Bio (NASDAQ: BLUE). The European Medicines Agency is expected to make a final decision on the gene therapy in coming months.
If approved, Zynteglo would be for a subset of patients with a severe form of beta thalassemia who are 12 years or older and can’t find a donor for a stem cell transplant. It would also be the first marketed treatment for Bluebird, which has been a key player in gene therapy’s recent renaissance.
Beta thalassemia is a rare disorder in which patients inherit a defective gene for coding hemoglobin, the oxygen-carrying protein in red blood cells. The effects depend upon the amount of normal hemoglobin the body manages to produce. Patients with “mild” thalassemia might not need help at all. The more severe cases are potentially deadly because of anemia that requires a lifetime of blood transfusions, often every two to four weeks. Repeated transfusions have their own risk: a dangerous buildup of iron that, in turn, requires iron chelation therapy to prevent organ damage, heart failure, or death. Bone marrow transplants are a potential cure, but they’re not available to everyone and have their own set of risks.
A single infusion of Zynteglo 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. In clinical trials, Zynteglo has shown the ability to free certain beta thalassemia patients from the need for regular blood transfusions—though, at this point, it’s unclear how long those effects will last. The most common side effects reported in clinical testing were low blood platelet counts, abdominal pain, non-cardiac chest pain, pain in the extremities, and difficulty breathing. That said, the Zynteglo procedure still requires a chemotherapy step called myeloablative conditioning that carries certain safety risks as well.
In a research note, SVB Leerink analyst Mani Foroohar wrote that the firm expects European regulators to approve Zynteglo within the next two months. Conditional approval would still require Bluebird to do additional testing to confirm the earlier results.
Bluebird has said it plans to file for U.S. approval of its beta thalassemia gene therapy this year. A Phase 3 study testing Zynteglo called Northstar 3 is ongoing, with updated results expected by the end of 2019.
Once on the market, Zynteglo could quickly face competition. Acceleron Pharma (NASDAQ: XLRN) and partner Celgene (NASDAQ: CELG) should soon file for approval of their beta thalassemia drug luspatercept in the U.S. and Europe. Luspatercept is also meant to boost hemoglobin and reduce the need for blood transfusions, but requires an infusion every few weeks. Bluebird will also have to overcome the commercial challenges that currently face gene therapy—namely, trying to convince payers to cover the high cost of a one-time procedure whose effects are uncertain. Bluebird has said it wants to use a five-year, installment plan for Zynteglo that ties continued payments to the drug’s effectiveness.
Frank Vinluan contributed to this report.