Beam preps FDA run for industry-first base-edited therapy after pivotal sickle cell success

Beam Therapeutics’ cell therapy risto-cel freed patients with sickle cell disease from severe pain crises for at least one year, teeing up what could be the first application for a base-editing therapy, possibly by the end of this year.

“Positive pivotal results strengthen the risto-cel regulatory case and mark an important milestone for base editing,” H.C. Wainwright said in a Tuesday morning investor note.

Ristoglogene autogetemcel—dubbed risto-cel—met the Phase 1/2 BEACON trial’s primary endpoint, Beam said on Tuesday, providing patients with sickle cell disease (SCD) with at least 12 consecutive months of freedom from severe vaso-occlusive crises (VOC)—or episodes of intense pain related to blocked vessels— based on independently adjudicated results. VOCs are a hallmark of SCD. As of Oct. 20, 39 adults and 10 adolescents had been treated with risto-cel, with 31 having completed the required follow-up period for the endpoint.

BEACON also succeeded on all secondary endpoints, which included freedom from hospitalization for severe VOCs for at least 12 consecutive months.

Risto-cel also met all of the trial’s primary safety endpoints at the interim analysis. The therapy’s profile was consistent with previously reported data from BEACON and with the known effects of the stem cell transplantation process.

In November 2024, Beam disclosed the death of a patient in BEACON, which according to the biotech occurred due to respiratory failure four months after receiving treatment. It was deemed unrelated to risto-cel and was instead “likely” linked to the busulfan-based chemotherapy immunosuppression regimen used in the stem cell transplant process.

The new Phase 1/2 readout will support an upcoming biologics license application (BLA), according to Beam. “With these results in hand, we are focused on submitting our planned BLA as early as year-end, which has the potential to be the first BLA for a base editing therapy,” Beam CEO John Evans said in a prepared statement.

While the FDA has approved gene-edited therapies from CRISPR Therapeutics and Genetix Biotherapeutics, Beam will likely be the first to seek marketing approval for a therapy that uses base editing. Also working on base editing is Eli Lilly, after the acquisition of Verve Therapeutics for up to $1.3 billion in 2025.

The biotech plans to present detailed results from BEACON at a medical meeting in 2027. BEAM will also present data from an earlier cutoff date at the American Society of Hematology (ASH) meeting in New Orleans next month.

H.C. Wainwright noted that Beam did not disclose safety details nor the proportion of patients who achieved the primary efficacy endpoint.

“The topline data establishes endpoint success, while detailed safety, response rates and longer-term outcomes remain the next focus,” the firm said.

Risto-cel, formerly known as BEAM-101, is an ex vivo, autologous therapy comprising autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) that have been base edited. SCD happens when a mutation in the beta-globin gene causes a mutated form of adult hemoglobin to collect into long, rigid molecules that bend red blood cells into a sickle shape, according to Beam. The edit in risto-cel is meant to inhibit the BCL11A gene from blocking expression of fetal hemoglobin, thereby increasing production of the non-sickling and anti-sickling version of the protein.

At ASH, H.C. Wainwright will be looking for fetal hemoglobin (HbF) induction of over 60% and reduction of sickle hemoglobin to lower than 40%—”a ‘60/40’ trait that is viewed by physicians and regulators as a key goal in the treatment of SCD.”

Last month, analysts named Beam as one potential beneficiary of the FDA’s new plug-and-play guidance, under which gene-editing therapies addressing various disease-causing mutations could be covered under one BLA.

The new draft guidance “converts the individualized ‘product variant’ concept into an operational licensing framework, with base editing the template modality,” H.C. Wainwright said in a note to investors late last month. The analysts specifically pointed to BEAM-304, currently in a Phase 1/2 trial for phenylketonuria (PKU). BEAM-304 is designed to correct mutations in the phenylalanine hydroxylase gene that cause the disease. In North America and Europe, there are thought to be four specific mutations that cause PKU.