Novartis partners with the Gates Foundation on one of the Holy Grails in gene therapy: a simple, in vivo approach to curing sickle cell disease
Having helped usher in a “new era” of sickle cell disease treatment with Adakveo, Novartis has set its sights on an even higher goal: a curative, relatively low cost, once-and-done in vivo gene therapy that can work in developing countries.
Tapping into the coffers of the Bill & Melinda Gates Foundation, the pharma giant says it will deploy its drug discovery and gene therapy experts in search of a product that can cater to regions with less resources. And they’re using today’s announcement to open its doors to any other groups that would like to pitch in.
Jay Bradner, who heads up the Novartis Institutes for BioMedical Research, tells Endpoints News that this collaboration dates back 5 years, when the pharma giant mapped out a sickle cell strategy running the gamut from access to currently available meds to an ex vivo gene edited stem cell approach to curing sickle cell disease, now in the clinic.
“It’s our job to look around the corner and imagine what the next wave of technology might be,” he says, “and this partnership with the Gates Foundation reflects one piece of that forward-thinking strategy — to imagine a singular therapeutic infusion of viral gene therapy to cure this disease.” They’ve learned a lot about CRISPRed approaches, which are tough to pull off in the most sophisticated medical centers. Now they want to develop tech that could be used practically anywhere, including the poorest countries in Africa, Asia and Latin America, which have little in terms of basic hospital infrastructure.
“Gene therapy is always about delivery,” notes Sue Stevenson, the executive director of hematology at NIBR, as investigators look to correct or repair a mutant gene, or insert a new one to do the job that was intended. “The first step is going to be figuring out the best way to deliver viral vectors to the stem cells in vivo with a single administration.”
NIBR will now have embedded labs dedicated to the task.
That’s a big, lengthy task, and it’s playing out as the leaders in the ex vivo side of R&D have experienced a lineup of complex challenges and safety threats that have delayed the arrival of the pioneers, in some cases raising doubts as to whether they can ever make it to the market in affluent countries.
The new partners are unveiling their collaboration just a day after bluebird bio, which has one of the leading gene therapies in the space, revealed it had halted sickle cell trials for LentiGlobin — including a Phase III — in order to investigate two new serious side effects among patients in the program.
Bluebird’s approach, like the CRISPR programs under development at Editas and Vertex/CRISPR Therapeutics, involves taking stem cells from patients and engineering them ex vivo before infusing the gene edited cells back into patients.
Biopharma companies, doctors and patients placed high hopes on these drugs because those currently on the market — including Novartis’ P-selectin-binding Adakveo and Global Blood Therapeutics’ sickle hemoglobin polymerization inhibitor Oxbryta — only reduce the frequency of painful vaso-occlusive crises but can’t fully protect patients from them, or the cumulative organ damage they can cause.
The focus research team within NIBR will now put all its efforts to coming up with an idea for a gene therapy that can “be administered once, directly to the patient, without the need to modify the cells in a lab.”
“Gene therapies might help end the threat of diseases like sickle cell, but only if we can make them far more affordable and practical for low-resource settings,” Trevor Mundel, president of global health at the Gates Foundation, added. “What’s exciting about this project is that it brings ambitious science to bear on that challenge. It’s about treating the needs of people in lower-income countries as a driver of scientific and medical progress, not an afterthought.”
It’s the same philosophy underlying the grant it gave Intellia Therapeutics, which is diverting from its CRISPR peers to research an in vivo way to edit stem cells.
The group didn’t disclose just how much research funding it’s handing to Novartis, but says it will lend its “long history and experience in global health to this collaboration.”
Notably, Novartis — whose first gene therapy, spinal muscular atrophy treatment Zolgensma, holds the dubious title of the world’s most expensive drug — says it will be bound by specific provisions to support global access to any resulting medicines.