FDA clears testing of potentially less toxic conditioning regimen for SCD
Iomab-ACT to be tested in patients before stem cell transplant
The U.S. Food and Drug Administration (FDA) gave the greenlight for Iomab-ACT, a potentially less toxic conditioning regimen, to be tested in people with sickle cell disease (SCD) undergoing a stem cell transplant.
The study will be conducted in collaboration between Actinium Pharmaceuticals, which is developing Iomab-ACT, and Columbia University in New York. It will be led by Markus Mapara, MD, PhD, a professor of medicine at Columbia’s Irving Medical Center.
If successful, the study is expected to inform a future clinical trial evaluating Iomab-ACT as a conditioning agent to be administered before gene therapy, for which there are two approved for SCD: Casgevy and Lyfgenia.
‘Success in this trial could revolutionize treatment’
“I am thrilled to lead this pioneering study using Iomab-ACT, a non-chemotherapeutic targeted radiotherapy conditioning, for patients with sickle cell disease,” Mapara, who is also the director of bone marrow transplantation and cell therapy program at Columbia’s Vagelos College of Physicians and Surgeons, said in a press release. “This innovative approach aims to minimize toxicity while ensuring complete donor … engraftment. Success in this trial could revolutionize treatment.”
In SCD, mutations in the HBB gene result in the production of a faulty version of hemoglobin, the protein in red blood cells that carries oxygen through the body. Faulty hemoglobin tends to form clumps, forcing red blood cells to adopt a sickle-like shape. The misshaped red blood cells are more prone to die prematurely and can obstruct blood vessels, causing patients to develop anemia and experience painful vaso-occlusive crises.
A stem cell transplant can potentially cure SCD. It involves replacing diseased stem cells, or those that give rise to red blood cells, with healthy stem cells from a matched donor (allogeneic transplant).
Other treatment options include gene therapies, such as Casgevy and Lyfgenia, both of which modify a patient’s own blood stem cells to produce functional hemoglobin.
Before either a stem cell transplant or gene therapy, patients must undergo a course of chemotherapy or radiation to destroy faulty stem cells in the bone marrow. This makes room for the healthy transplanted cells to grow and multiply.
However, pretransplant conditioning is associated with serious complications, which limits the number of SCD patients who may pursue transplant or gene therapies.
Current conditioning regimens come with severe side effects
“Undergoing chemotherapy or total body irradiation-based conditioning for curative allogeneic bone marrow transplant or gene therapy often brings severe side effects for patients with sickle cell disease,” Mapara said. “These toxicities include organ damage, infections, infertility, and the potential for secondary malignancies.”
Actinium first developed Iomab-B, which is composed of apamistamab, an antibody that targets CD45, a protein found on the surface of blood cancer cells and immune cells. Attached to it is iodine-131, a short-lived isotope that releases radiation to kill adjacent cells.
Iomab-B showed promise in multiple clinical trials in more than 300 patients undergoing a bone marrow transplant for various types of blood cancers, according to the company.
Iomab-ACT is a next-generation agent that also contains apamistamab, but uses lower levels of iodine-131 to achieve cell depletion. The new trial will evaluate the safety of Iomab-ACT in SCD patients who are about to receive an allogeneic bone marrow transplant.
“We are honored to collaborate with Dr. Mapara on this important initiative to address the significant number of patients with sickle cell disease who do not pursue or are not able to access transplant or gene therapies due to the required chemotherapy-based conditioning and its severe toxicities,” said Sandesh Seth, Actinium’s chairman and CEO. “We look forward to further expanding Iomab-ACT’s already large addressable patient opportunity in transplant, cell therapy and gene therapy conditioning.”
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