Beam Therapeutics reports that after a single infusion of a DNA editor, blood sugar in two patients with glycogen storage disease type Ia (an inherited disorder in which the liver releases too little glucose into the blood) stayed above the dangerous level through 15 hours without food

Beam Therapeutics reports that after a single infusion of a DNA editor, blood sugar in two patients with glycogen storage disease type Ia (an inherited disorder in which the liver releases too little glucose into the blood) stayed above the dangerous level through 15 hours without food

On October 13, Beam announced the first data from an early-stage Phase 1/2 trial of BEAM-301. Six adults each received a single infusion: three at a dose of 20 mg and three at 40 mg. The figures are as of June 26, and Beam will present updated data on October 28.

In glycogen storage disease type Ia, mutations in the gene for the enzyme glucose-6-phosphatase disrupt how the enzyme works. As a result, the liver releases less glucose into the blood, and blood sugar falls between meals. Patients take cornstarch day and night as a backup source of glucose. The R83C mutation, a change in a single DNA "letter", is among the most common mutations and causes the most severe form of the disease. Without cornstarch, these patients can go into hypoglycemic shock, a dangerous drop in blood sugar, within one to three hours.

BEAM-301 consists of lipid nanoparticles, which are small fat capsules. After intravenous infusion they enter liver cells and deliver two cargoes: an mRNA that the cell uses to build the editor protein, and a guide RNA that directs the editor to the right place in the gene. The editor nicks one of the two DNA strands and replaces a single letter. The corrected gene is then expected to encode a normal enzyme.

BEAM-301 grew out of a 2024 study in mice that included Beam scientists among its authors. The authors noted two problems with earlier approaches. Previous attempts to correct this gene in mice with CRISPR that cuts both DNA strands produced fewer than 2% corrected gene copies, and for virus-based gene therapy there were not enough data on whether the added gene keeps working for a lifetime. In mice carrying the human R83C mutation, BEAM-301 corrected up to 60% of gene copies. Untreated mice became hypoglycemic after 60–75 minutes of fasting, while treated mice tolerated a full day without food, and the effect lasted a year.

The patients were also tested with a controlled fast. Before treatment, the median time until blood sugar fell to a dangerous level was 2.9 hours in the 20 mg group and 2.5 hours in the 40 mg group. By day 36 after infusion, the median in the 20 mg group had risen to 4.3 hours. In the 40 mg group, efficacy had been assessed in two of the three patients by the data cutoff, and by the same day both had fasted for 15 hours or longer. The trial protocol stops the test at this limit, so the true duration may be longer. Beam considers the result in the 40 mg group consistent with the body restoring its own glucose production.

The median follow-up was 313 days in the 20 mg group and 53 days in the 40 mg group. In the 40 mg group, the prescribed daily cornstarch dose fell by 71% by day 50 and by 92% by day 93, and the number of doses per day dropped by 2 to 4 from a baseline of 5 to 6. For the 20 mg group, Beam gives three values: 74% by day 128, 71% by day 227 and 11% by day 387, with 0 to 4 fewer doses per day from a baseline of 6 to 7.

All six patients had at least one adverse event related to the drug. Five adverse events were serious; three of them were severe (grade 3) infusion reactions. All five resolved within 2–10 days. Beam suggests that the short-acting steroids given before the infusion may have contributed to the severe reactions, and the company has already changed how it uses them. No deaths occurred, and no patient stopped treatment because of adverse events.

For the same disease, the FDA granted accelerated approval on August 19 to Ultragenyx's therapy GENGLYCOS. It uses an AAV8 viral vector to deliver a working copy of the gene into liver cells, where the copy remains mostly separate from the chromosomes. The approval rests on a reduction in daily cornstarch intake, the same measure Beam tracks. Patients who already have antibodies against AAV8 cannot receive GENGLYCOS. BEAM-301 corrects the letter in the gene itself and is designed for a single mutation, R83C.