Drugs

FDA Sets Higher Approval Bar for Passage Bio Dementia Therapy

FDA has told Passage Bio that a randomized controlled trial will be required to support approval of its experimental gene therapy for a rare form of dementia, raising the regulatory bar as the company evaluates the future of the program. The feedback, delivered during a recent Type C meeting, means the company cannot rely on a single-arm study using natural history comparisons — a pathway sometimes pursued in rare diseases — instead must conduct a more complex and resource-intensive registrational trial.

The advice comes as Passage Bio reported updated interim data from its ongoing Phase 1/2 upliFT-D trial of PBFT02 in patients with frontotemporal dementia linked to granulin mutations. The company says treated patients showed improvements in key biomarkers associated with disease progression, particularly among those in earlier stages of illness.

At 12 months, patients with less advanced disease experienced a 64% reduction in whole brain atrophy and a 54% reduction in frontotemporal cortex atrophy compared with untreated patients in natural history datasets, according to the company. In addition, levels of neurofilament light chain — a marker of neuronal damage — remained stable in treated patients, while rising in untreated individuals.

PBFT02 is designed to restore progranulin levels, and the company reports sustained increases in the protein in cerebrospinal fluid for up to 18 months. A lower-dose cohort appeared to achieve similar protein expression levels as a higher dose. However, no meaningful benefit was observed in patients with more advanced disease, narrowing the potential target population.

Passage Bio notes that FDA’s requirement for a randomized controlled trial introduces significant ethical and logistical challenges, particularly in a progressive and underserved disease where patients may be reluctant to receive placebo. The company is now reassessing its development strategy for PBFT02 in both granulin-related and other forms of frontotemporal dementia.

Gupta Raises Concerns About Overton’s Independence, Ideology

FDA commissioner nominee Heidi Overton’s responses on vaccines, contraception and abortion medication during her 9/24 Senate confirmation hearing raise concerns that ideology could influence her decision-making if she takes over the agency, MSNBC senior medical analyst Dr. Vin Gupta said Friday. Gupta was particularly critical of Overton’

Overton Confirmation Remains Uncertain After Senate Hearing

FDA commissioner nominee Heidi Overton emerged from her Senate confirmation hearing Thursday (see earlier story) without resolving questions about whether she has enough Republican support to advance — and with a rapidly narrowing window for confirmation before the midterm elections. The Senate Health, Education, Labor and Pensions Committee hearing provided few

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA has classified Boston Scientific's recall of its Imager II Angiographic Catheters as Class I because a manufacturing problem could cause catheter tips to degrade and detach, potentially resulting in life-threatening complications. The agency announced the Class I classification 9/25, updating an Early Alert it issued

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome

FDA has approved Roche’s Gazyva (obinutuzumab) for reducing the risk of relapse in adults and children aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome who are in remission. The expanded approval covers the use of the CD20-directed antibody beyond its existing

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Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome