advanced therapies head for the clinic

A fresh wave of gene-editing therapies is surging to the fore — even as the field wrestles with the challenge of getting the first generation of expensive and complex CRISPR treatments to the people who need them.

Barely a year after the first government approval for a gene-editing therapy, researchers at the American Society of Hematology’s annual meeting in San Diego, California, presented data on gene-editing approaches for treating cancer and blood disorders, and for making stem-cell transplants safer. They also unveiled good news about the first approved treatment: benefits from the therapy, called Casgevy, can last for at least five years in people with either of two heritable blood disorders, sickle-cell disease and β-thalassaemia. Casgevy gained its first government approval little more than a year ago.

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Casgevy had “a clear benefit in general health, physical, emotional, social and functional well-being,” said Franco Locatelli, a paediatric haematologist and oncologist at Bambino Gesù Children’s Hospital in Rome, who presented the data. The therapy, he added, has “the potential to provide a one-time functional cure”.

But although other companies are rushing to emulate Casgevy’s success, the treatment’s complexity and hefty price tag have raised concerns that it will be out of reach for many people.

Stuart Orkin, a paediatric haematologist and oncologist at the Harvard Stem Cell Institute in Cambridge, Massachusetts, said at the meeting, “The imperative now is development of effective and safe therapies that are readily accessible to the many patients who could benefit.”

Fetal form to the rescue

Both β-thalassaemia and sickle-cell disease are caused by mutations in one of the genes that code for haemoglobin, the oxygen-carrying molecule found in red blood cells. A different, fetal form of haemoglobin can help to compensate for the effects of these mutations, but its production is typically turned off shortly after birth. Casgevy uses CRISPR–Cas9 to disable that genetic off-switch, allowing fetal haemoglobin to be produced again.

Last November, the United Kingdom became the first country to approve Casgevy. The US Food and Drug Administration followed suit in December, and several other countries have since approved the therapy. More than 45 treatment centres around the world have been authorized to provide Casgevy, according to its developers, Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Zug, Switzerland.

But the treatment must be made from an individual’s own blood stem cells, a process that can take months. And countries are still grappling with how to incorporate the cost of the US$2.2-million therapy into their health-care budgets.