NIH, Gates Foundation aim to bring genetic cures to the poor – STAT

The National Institutes of Health and the Bill and Melinda Gates Foundation will together invest at least $200 million over the next four years to develop gene-based cures for sickle cell disease and HIV with an attribute even rarer in the world of genetic medicine than efficacy, the groups announced on Wednesday: The cures, they vowed, will be affordable and available in the resource-poor countries hit hardest by the two diseases, particularly in Africa.

The effort reflects growing concerns that scientific advances in genetic medicine, both traditional gene therapies and genome-editing approaches such as CRISPR, are and will continue to be prohibitively expensive and therefore beyond the reach of the vast majority of patients. Spark Therapeutics’ Luxturna, a gene therapy for a rare form of blindness, costs $425,000 per eye, for instance, and genetically engineered T cells (CAR-Ts) to treat some blood cancers cost about the same.

With CRISPR-based treatments already being tested in clinical trials for sickle cell disease, the blood disorder beta thalassemia, and another form of blindness, and with additional CRISPR treatments in development, scientists, ethicists, and health policy experts have grown increasingly concerned that the divide between haves and have-nots will grow ever-wider.


Gene-based treatments “are largely inaccessible to most of the world by virtue of the complexity and cost of treatment requirements, which currently limit their administration to hospitals in wealthy countries,” the NIH said in a statement. To help right that, its collaboration with the Gates Foundation aims to develop “curative therapies that can be delivered safely, effectively and affordably in low-resource settings.”

Scientists whose research focuses on gene-based cures welcomed the infusion of funding and the recognition that genetic cures are on track to be unaffordable to the majority of patients. But they noted one irony. The most effective sickle cell drug, hydroxyurea, has hardly even been studied in sub-Saharan Africa, let alone made widely available. Yet a 2019 study found that giving children the drug cut their death rate by two-thirds and halved the pain crises that are common in sickle cell disease, caused by misshapen red blood cells that cannot flow through blood vessels.

The NIH-Gates collaboration “is tremendously exciting and has the potential to have a great impact on sickle cell disease in sub-Saharan Africa,” said Dr. Vijay Sankaran of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, who has done pioneering research on genetic cures for the disease. “But my hesitation is that even the inexpensive therapies we have today, such as hydroxyurea, are largely unavailable there. The question is, how do we best approach this disease, with therapies that are working today or with genetic therapies that might work?”

The same concerns surround HIV. Very inexpensive — less than $100 per year in the U.S. — antiretroviral drugs can keep the virus in check, but only 67% of HIV-positive adults and 62% of HIV-positive in children in east and southern Africa are estimated to be on antiretroviral treatment.

The new collaboration aims to move gene-based cures into clinical trials in the U.S. and countries in sub-Saharan Africa within the next seven to 10 years, and to eventually make such treatments available in areas hardest hit by sickle cell disease and HIV/AIDS. The idea is to focus “on access, scalability, and affordability … to make sure everybody, everywhere has the opportunity to be cured, not just those in high-income countries,” NIH Director Francis Collins said in a statement. “We aim to go big or go home.” But the challenge is enormous, he told reporters on Wednesday: “I’m not going to lie. This is a bold goal.”

An estimated 95% of the 38 million people with HIV live in the developing world, with 67% in sub-Saharan Africa. Up to 90% of children with sickle cell disease in low-income countries die before they are 5 years old. In the U.S., the life expectancy for people with sickle cell disease is in the low 40s.

The NIH and the Gates Foundation will fund research to identify potential gene-based cures for sickle cell and HIV, and also work with groups in Africa to test those cures in clinical trials.

The science of genetic cures for both diseases is within reach, experts say. CRISPR Therapeutics and Vertex (VRTX) are already running a clinical trial for sickle cell disease, using the CRISPR genome editor to do an end-run around the disease-causing mutation in the hemoglobin gene: The therapy releases the brake on red blood cells’ production of fetal hemoglobin, whose production shuts off in infancy but which does not have the sickling damage of adult hemoglobin.

Developing effective, safe genetic cures for sickle cell and HIV would be only a first step, however. As currently conceived, such therapies require advanced medical facilities to draw blood from patients, alter their cells’ genomes in a lab, give the patients chemotherapy to kill diseased blood-making cells, and then perform what’s essentially a bone marrow transplant, followed by monitoring patients in a hospital for days to prevent infection and provide intensive medical support, said Dr. Dan Bauer, a sickle cell expert at Boston Children’s.

He called the NIH-Gates effort “terrific,” but cautioned that delivering advanced gene therapies requires “tremendous effort, extended hospitalization, and large supplies of blood products.” All of those requirements mean that even if a CRISPR-based cure for sickle cell disease or HIV were provided at cost, “there will still be barriers to access.”

Recognizing that, Collins said, a genetic cure would have to be given directly into patients (“in vivo”), presumably through an infusion, rather than by treating blood or other cells removed from patients and genetically transformed in a lab (“ex vivo”). That could avoid “the resources needed for and the complications that can occur with ex vivo therapies,” said Sankaran, who has discussed the approach with Gates officials.

This story has been updated with additional comments.

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