Noted This Week
A new framework outlines how the FDA plans to incorporate real-world evidence (RWE) into the drug review process. Per the framework, the agency will consider RWE for the approval of new indications for already-approved drugs, and to satisfy post-approval study requirements. The FDA will use a three-part approach, which includes steps like assessing real-world data and the studies that generated them, when determining whether RWE is appropriate to answer a regulatory question.
In a paper in Science, researchers identified molecular features of glioblastoma that are associated with specific clinical outcomes. Researchers performed genomic sequencing on 416 neuroblastoma tumors and assessed telomere maintenance mechanisms in 208 of the tumors. They found that low-risk tumors lacked telomere maintenance mechanisms, whereas intermediate-risk tumors had the maintenance mechanisms, and high-risk tumors had the maintenance mechanisms plus RAS and/or p53 pathway mutations.
MacroGenics announced that the FDA ordered a partial clinical hold on MGD009, a bispecific Dual-Affinity Re-Targeting molecule that targets B7-H3 and CD3. The hold came after the company reported liver-related side effects in a phase I trial testing the drug as a monotherapy in patients with various solid tumors. The company will halt enrollment in this trial and another phase I trial testing the drug in combination with the experimental anti–PD-1 therapy MGA012.
The FDA granted an orphan drug designation to M7824 (EMD Serono) for biliary tract cancer. In a phase I trial, 30 patients treated with the drug after their cancer worsened on platinum-based first-line therapy had an overall response rate of 20%, with responses ranging from 8.3 to more than 13.9 months. M7824 is an experimental bifunctional immunotherapy that combines an anti–PD-L1 mechanism with a TGFβ trap.
Roche announced that it will develop a pan-cancer companion diagnostic to detect mismatch repair deficiency in solid tumors. The test will be used to identify adult and pediatric patients with inoperable or metastatic solid tumors who may benefit from Merck’s anti–PD-1 therapy pembrolizumab (Keytruda), which was the first drug FDA approved based on a common biomarker rather than tumor type.
The debate over the use of fetal tissue in research continued at a meeting of the NIH’s Advisory Committee to the Director, during which NIH director Francis Collins, MD, PhD, said that although the agency will spend up to $20 million on research alternatives, "there is strong evidence that scientific benefits can come from fetal tissue research, which can be done with an ethical framework." Meanwhile, the NIH announced that the government-mandated freeze on fetal tissue procurement put in place in September may soon impede cancer research in at least one lab at the NCI.
Cancer Research UK and AstraZeneca announced the launch of the Joint Cancer Research UK–AstraZeneca Functional Genomics Center, to be located at the University of Cambridge in the UK. Research at the center will focus on how technologies such as CRISPR can be used to advance research on cancer genetics, and to identify and test potential drug targets.