The sickle cell disease (SCD) treatment market, while invigorated by recent gene therapy approvals, faces significant hurdles in patient access and treatment options. The withdrawal of Pfizer's Oxbryta due to safety concerns and slow patient uptake of gene therapies have underscored the need for more accessible and less complex treatments.
Gene Therapy Limitations
Two gene editing medications, including the first FDA-approved CRISPR-based drug Casgevy from Vertex Pharmaceuticals and CRISPR Therapeutics, and Lyfgenia from bluebird bio, have been approved for sickle cell indications, offering potentially curative care. However, these therapies come with multimillion-dollar price tags and a complex, months-long ex-vivo process. This process includes extracting stem cells from bone marrow, sending them to manufacturers for modification, and undergoing chemotherapy to prepare for the edited cells.
Dr. Cameron Trenor, head of translational medicine for Cellarity, noted, "They've been considered a functional cure in the field. However, they're challenged by cost, complexity, and toxicity of delivery. It seems hard to get around that safety barrier and the scalability challenges given the cost and complexity of manufacturing."
As of the end of September, only 10 patients had started on Lyfgenia this year. Bluebird bio recently announced plans to lay off about a quarter of its workforce to cut costs. Furthermore, a study revealed seven children developed blood cancer after receiving Skysona, bluebird’s gene therapy for a rare brain disease, recalling when bluebird temporarily suspended trials for Lyfgenia after two patients developed cancer in 2021.
Setbacks in the Pipeline
The sickle cell pipeline has faced other setbacks. Graphite Bio abandoned its lead asset, a sickle cell gene editing therapy, after a severe adverse event occurred in the first dosed patient. Kamau Therapeutics is attempting to revive that asset, while Graphite Bio has merged with Lenz Therapeutics.
Unmet Needs and Market Potential
Despite these challenges, the sickle cell disease market remains attractive due to significant unmet medical needs. According to a consensus forecast from Evaluate, the market has potential sales of $5 billion in 2030, even with Oxbryta’s withdrawal.
"This is a profoundly devastating disease. It's essentially a disease of hypoxia: not being able to get oxygen to your tissues well," said Trenor. "That manifests in silent and painful ways."
Sickle cell disease can affect any part of the body, causing stroke, heart disease, lung disease, spleen damage, liver disease, and kidney disease.
Alternative Treatment Approaches
Several companies are developing alternative treatments. Cellarity is in the IND-enabling phase with an oral drug designed to induce fetal hemoglobin production. The company plans to start clinical trials next year, aiming to provide a more accessible treatment option.
"It is known from patients with mutations that have genetically high fetal hemoglobin, that if you can get over about 20% fetal hemoglobin you don't have many complications of sickle cell disease any longer," Trenor said. "We're hoping we'll be able to get patients up to or above that level with a small molecule, and that would be a paradigm shift in the field."
Other companies, including Novo Nordisk, Agios Pharmaceuticals, and GSK, are also developing sickle cell treatments. Agios Pharmaceuticals has completed enrollment for a phase 3 study of its oral, small molecule PK activator, while GSK is in early development with its DNMT1 inhibitor.
The Future of Sickle Cell Disease Treatment
The approvals of CRISPR/Vertex and bluebird bode well for the chances of some of these next-generation cell therapies, and this competition will help to improve patient access. The Oxbryta withdrawal leaves the market with limited non-gene therapy drugs, including hydroxyurea, which carries safety risks due to immunosuppression.
Cellarity hopes its oral treatment will help bridge the access divide. "The disease is not going away, and we need something that all or almost all patients can take," Trenor said.
