Verve Therapeutics now has the official FDA filing detailing what the regulator wants to see before allowing the company to begin human testing of its gene-editing therapy for an inherited form of high cholesterol.
VERVE-101 is designed to turn off PCSK9, a gene that produces a liver protein that makes it harder for the body to clear low-density lipoprotein, the “bad” form of cholesterol. Patients have already been dosed in a clinical program taking place in New Zealand and the UK Last month, the FDA placed a clinical hold on the Cambridge, Massachusetts-based company’s new drug application for a US trial.
The FDA wants to see more preclinical data on the differences in efficacy between human and non-human cells, as well as additional data on the risks of changes made by the therapy being inherited by the patient’s children, Verve said Monday regulatory submission. The FDA asked Verve to modify the US clinical trial protocol to include additional contraceptive measures and increase the length of time between patient dosing.
The FDA also has concerns about off-target effects. The filing states that the agency has asked the company to provide analyzes of data showing whether the effects of the therapy reach cell types outside of liver cells. In addition, the FDA asked to see the data available so far from New Zealand and the United Kingdom. These data were not part of the original submission to the FDA. Verve said enrollment is ongoing in these regions and the company plans to report initial safety and pharmacodynamic data from the dose-escalation portion of the trial in the second half of 2023. Without specifying a timeline, the company said it plans to send a response to the FDA information requires “as expeditiously as possible.”
The lifting of a clinical hold on another experimental genetic drug was among other recent regulatory news last week, which included two drug approvals and one rejection. Here is a summary of these developments:
— FDA lifted clinical hold released in investigational new drug application for Beam Therapeutics’ gene-edited cell therapy for acute lymphoblastic leukemia. The FDA put the BEAM-201 program on hold in August. With the hold lifted, the Cambridge, Massachusetts-based biotech now has permission to proceed with human testing. BEAM-201 is an off-the-shelf cell therapy that uses four edits made with base editing technology. Beam said it will provide details on the program’s next steps in 2023.
— FDA approved first treatment of fecal microbiota to prevent the recurrence of Clostridioides difficile (C. misc) infection in adults who have completed a course of antibiotics for the potentially fatal infection. The A product by Ferring Pharmaceuticals called Rebyota, is made from feces provided by qualified donors. This rectally administered live biotherapeutic aims to restore the gut microbiome, which in turn prevents episodes of C. misc infection.
— Drug Rigel Pharmaceuticals won FDA approval for the treatment of acute myeloid leukemia (AML) with a specific genetic signature. The South San Francisco-based biotech will commercialize the drug, olutasidenib, under the name Rezlidhia. The small molecule is designed to target mutated isocitrate dehydrogenase-1 (IDH1), an enzyme found in cancer cells. Blocking this enzyme aims to restore normal myeloid cell differentiation. The regulatory decision for Rezlidhia covers the treatment of adults whose AML has an IDH1 mutation detected by an FDA-approved test.
— FDA rejected Application Y-mAbs Therapeutics seeking approval for its drug to treat a rare pediatric brain cancer. The drug, omburtamab, was developed to treat leptomeningeal metastases, which is the spread of neuroblastoma from the brain to the membranes surrounding the brain and spinal cord. The negative regulatory decision came just over a month after an independent advisory panel to the FDA voted unanimously that New York-based Y-mAbs did not provide enough evidence to show that the clinical program, which compared omburtamab to a historical control group, improved overall survival in patients.
— Eli Lilly’s Covid-19 drug bebtelovimab is is no longer authorized for use anywhere in the US According to the FDA, the change was made because the antibody is not expected to work against the BQ.1 and BQ.1.1 subvariants of omicron, which together account for 57% of all cases nationally. Revoking the Lilly drug’s emergency use authorization removes the last remaining monoclonal antibody drug against Covid-19 from the market.
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