Beam Therapeutics Inc. announced that the U.S. Food and Drug Administration has granted orphan drug designation to BEAM-101, an investigational genetically modified cell therapy for treating sickle cell disease. The designation supports development of treatments for rare diseases affecting fewer than 200,000 people in the United States.
"Sickle cell disease is a devasting disorder that affects approximately 100,000 people in the U.S., leading to anemia, severe pain, stroke and even early death," said Amy Simon, M.D., chief medical officer of Beam Therapeutics. "Receiving orphan drug designation from the FDA emphasizes the importance of new treatment options for this debilitating disease, and our clinical data suggest that BEAM-101, the lead program in our hematology franchise, has the potential to offer a differentiated, best-in-class treatment."
Clinical Trial Results Show Promise
Data from seven patients treated with BEAM-101 in the BEACON clinical trial were presented at the 66th American Society of Hematology Annual Meeting and Exposition in December 2024. Treatment with BEAM-101 demonstrated robust and durable increases in fetal hemoglobin (HbF) and reductions in sickle hemoglobin (HbS), rapid neutrophil and platelet engraftment, and normalized or improved markers of hemolysis.
The initial safety profile of BEAM-101 was consistent with busulfan conditioning and autologous hematopoietic stem cell transplantation. Updated clinical data have been accepted for presentation at the European Hematology Association 2025 Congress in June.
Advanced Manufacturing Process
Manufactured in Beam's North Carolina facility, BEAM-101 uses an advanced, largely automated process that has demonstrated consistently high yields and viability, enabling successful BEAM-101 manufacturing for patients in the BEACON clinical trial. Beam expects to dose 30 patients in the ongoing BEACON trial by mid-2025.
Innovative Base Editing Approach
BEAM-101 is a one-time therapy consisting of autologous CD34+ hematopoietic stem and progenitor cells that have been base-edited in the promotor regions of the HBG1/2 genes and are administered via a hematopoietic stem cell transplant procedure. The BEAM-101 edit is designed to inhibit the transcriptional repressor BCL11A from binding to the promoter without disrupting BCL11A expression, leading to increased production of non-sickling and anti-sickling fetal hemoglobin.
This approach mimics the effects of naturally occurring variants seen in hereditary persistence of fetal hemoglobin. HbF is the predominant hemoglobin variant during development and early life.
Regulatory Benefits and Market Impact
The FDA's orphan drug designation comes with potential benefits for Beam Therapeutics, including tax credits for qualified clinical trials, exemption from user fees, and a potential seven years of market exclusivity after approval.
The BEACON Phase 1/2 study is an open-label, single-arm, multicenter trial in adult patients with sickle cell disease with severe vaso-occlusive crises. Sickle cell disease is caused by a single point mutation, E6V, in the beta globin gene, causing mutated sickle hemoglobin to aggregate into long, rigid molecules that bend red blood cells into a sickle shape under low oxygen conditions.
Sickled cells obstruct blood vessels and die prematurely, ultimately resulting in anemia, severe pain, infections, stroke, organ failure and early death. The disease affects an estimated 100,000 individuals within the United States and approximately eight million people worldwide, making it the most common inherited blood disorder in the United States.
