The benefit, and risk, of a CRISPR cure for children with sickle cell disease or beta thalassemia
The CRISPR-based therapy called Casgevy has the potential to be curative for children younger than 12 who are born with either of two inherited blood disorders, beta thalassemia and sickle cell disease, according to preliminary results from clinical trials presented here.
But a child with beta thalassemia died from pneumonia and organ failure caused by the toxic chemotherapy required to prepare the participant for Casgevy, underscoring the safety risk of the one-time genetic treatment marketed by Vertex Pharmaceuticals and CRISPR Therapeutics.
In children aged 5-11 with sickle cell, 11 patients have been treated with Casgevy in Vertex's Phase 3 clinical trial. Of those, four of four with sufficient follow up have been free from vaso-occlusive pain crises for at least 12 months. None of the study participants to date have experienced a pain crisis since receiving Casgevy.
Thirteen children in the same age range with beta thalassemia have also received Casgevy in a separate Phase 3 study. Of those, six of six with sufficient follow up have become blood-transfusion independent for at least 12 months.
At a press briefing, Haydar Frangoul, a pediatric hematologist at the Sarah Cannon Research Institute and an investigator in the studies, said the results, while preliminary, suggest Casgevy could be even more beneficial for younger children than for adults by providing a functional cure for the two blood disorders before organ damage accumulates.
Casgevy was initially approved in 2023 for adolescents and adults with sickle cell and beta thalassemia. Commercial uptake has been slow, however, due to the complicated, months-long process required to make and receive the treatment. Some people choose not to undergo treatment because of the toxicity of the chemotherapy regimen required to prepare them for Casgevy. Vertex is conducting the two Phase 3 studies seeking to expand Casgevy's use to younger children, with a regulatory filing expected in the first half of next year, the company said. Recently, FDA Commissioner Marty Makary awarded Vertex a "National Priority Review" voucher that will shorten the Casgevy review to 1-2 months.
Hematology as a research foundry for breakthrough treatments
From targeted cancer drugs to cell therapies, some of the greatest advances in medicine have originated in hematology. At a STAT event on Friday evening, industry leaders underscored why hematology research can reverberate far beyond the bloodstream.
Studying the basic biology of blood cancer has proven to be a powerful lens into broader disease mechanisms. "Blood cancer is uniquely positioned because we're really studying both the malignant cell and the healthy immune system, or how the malignant environment affects the healthy immune system, at the same time. We're just learning so much more," said Lore Gruenbaum, chief scientific officer and senior vice president of research at Blood Cancer United.
Yusri Elsayed, global oncology therapeutic area head for Johnson & Johnson, explained that hematology has long been an engine of innovation for the company's oncology pipeline, and increasingly for other therapeutic areas as well.
J&J is exploring cell therapy in neurological diseases like multiple sclerosis and in autoimmune diseases, where the same CAR receptors J&J used in multiple myeloma are being used to treat abnormal B cells in lupus patients.
"The hematologists always lead — we keep leading and bringing them into new places," Elsayed said.
Lynelle Hoch, president of Bristol Myer Squibb's cell therapy division, and Cindy Perettie, president of Kite Pharma, the cell therapy unit of Gilead Sciences, shared the stage to discuss the future of CAR-T therapy.
Currently, only two of every 10 patients with lymphoma and eligible for a CAR-T treatment receive one. While they compete against each other, Perretie and Hoch agreed that there is still work to be done collectively to bring CAR-T therapy to community hospitals, where the majority of lymphoma patients are treated.
Looking ahead, both Bristol and Gilead are investing in emerging technologies, including the in-vivo delivery of CAR-T, that could eliminate some of the bottlenecks that have hindered patient access.
Moving CAR-T from blood cancer and into other disease areas is also an important strategic push for both companies.
Kite has invested in a startup that is developing a cell therapy for Parkinson's disease.
For Hoch, a recent rheumatology meeting was a "mic drop moment" for CAR-T cell therapy in autoimmune disease.
Hoch told the story of a patient with debilitating and chronic myositis whose disease was essentially eradicated by a one-time infusion of an experimental Bristol CAR-T therapy. The patient showed up at a poster session during the rheumatology meeting because it was important for her that scientists see the impact these treatments can have on real people, and not just see data on a chart, Hoch recounted.
Adam Feuerstein/STAT
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