Biologics

Lessons Learned from Gene Therapies: CBER Official

FDA’s limited experience in approving seven gene therapies to date has provided some valuable “lessons learned,” according to CBER Office of Tissues and Advanced Therapies director Wilson Bryan. Speaking at a 12/6 online update for the Alliance for a Stronger FDA, Bryan said all seven products were approved based on data from single-arm studies because they had large effect sizes. “If there's a large effect size, the clinical trials don't need to be big, and we can do clinical trials in small populations,” he told the Alliance.

Bryan said that two gene therapy approvals — Spark Therapeutics’ Luxturna (voretigene neparvovec-rzyl) and Novartis’ Zolgensma (onasemnogene abeparvovec-xioi) — were approved based on two trials each and totaling 36 patients in each approval. Zolgensma used natural history controls, he said, adding that “(w)hen you have good natural history data and you have a huge effect size then natural history controls and small studies are feasible. We need more natural history studies, and we need to design clinical trials for these rare diseases.”

The science has advanced to the point where huge effects can be seen, and this means that the first-in-human studies of gene therapy products need to be randomized because it could provide evidence of effectiveness to support a marketing application, according to Bryan. “We need to stop thinking about doing Phase 1 and Phase 2, then Phase 3 studies in rare diseases,” he observed. “There simply aren't enough patients for that paradigm because of the huge unmet need and people can't wait.”

And regarding the speed of product development, Bryan said that what’s holding up approvals in many cases is chemistry, manufacturing and controls (CMC) and other manufacturing issues. “We really need for sponsors to start working on CMC issues earlier and potency assays are a particular challenge,” he said. “You’ve got to understand your product and you’ve got to figure out its mechanism of action and develop a good potency assay as early as possible in development.”

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