After being ordered to pay more than $572 million in August when it was the only opioid manufacturer left standing in a public nuisance trial in Oklahoma, Johnson & Johnson (J&J) and its subsidiaries are not risking a similar outcome in Ohio. J&J disclosed Monday that it agreed to a $10 million settlement with Cuyahoga and Summit Counties with no admission of liability. In exchange for bowing out of the federal multidistrict litigation slated to go to trial in a few weeks in Ohio, the New Brunswick, N.J.-based company also will reimburse the counties $5 million for legal and other trial preparation expenses, and it will direct $5.4 million of its charitable contributions to nonprofit organizations offering opioid-related programs in the two counties. In announcing the settlement, J&J reiterated that it's open to an "appropriate, comprehensive resolution" of all U.S. opioid litigation, but it's prepared to defend what it called its "responsible marketing" of the Duragesic (fentanyl) patch, Nucynta (tapentadol) and Nucynta ER, which, since their launch, have accounted for less than 1% of total opioid prescriptions in the U.S. J&J sold the U.S. marketing rights for Nucynta four years ago and stopped marketing Duragesic in the U.S. in 2008. J&J's settlement in the Ohio Track 1 cases follows Mallinckrodt plc's announcement Monday that it had reached a $24 million settlement with the two counties. (See BioWorld, July 8, 2015, and Aug. 28, 2019.)

Novel statistical methods used to extract, analyze and interpret real-world data and patient-level trial data must be tested and validated much like a new drug would be if regulators are to rely on the data in their decisions, EMA experts said in an article in Clinical Pharmacology & Therapeutics. Validation of the methods will need to be built into the development plans for some new drugs, the EMA said. One way forward is to validate the analytical methodologies using the agency's qualification procedure, ideally with the participation of health technology assessment bodies, payers and patient groups.

The FDA finalized its 2015 guidance on the nonclinical assessment of investigational enzyme replacement therapies (ERTs). The guidance is intended to expedite the development of ERT products used to treat rare, life-threatening conditions, especially in children. "The nonclinical study requirements for ERT products may be different from products used to treat other diseases because of the rare, seriously debilitating and life-threatening nature of the diseases," the FDA said. Changes made in the final guidance include the addition of statements on recovery animals, the preference for animal disease models in assessing pharmacodynamic activity and the three-month toxicology study in one species to support marketing approval. Other revisions include "changes in disease-specific biomarkers" being added as a pharmacodynamic endpoint and the addition of pharmacology parameters to proof-of-concept studies.

In investigating prescription and over-the-counter antacid drugs containing ranitidine for N-nitrosodimethylamine (NDMA), a possible carcinogen, the FDA said it found that the method for testing for the nitrosamine impurities in angiotensin II receptor blockers actually generates high levels of NDMA when it is used to test ranitidine. The method heats the sample to high temperatures, which produces high levels of NDMA in ranitidine. Consequently, the FDA is recommending that manufacturers of ranitidine products use an LC-HRMS protocol to test samples as it doesn't use elevated temperatures. The LC-HRMS protocol has shown much lower levels of NDMA in ranitidine samples than those reported by a third-party laboratory using the high temperature test. After conducting their own tests, manufacturers should send samples of their ranitidine products to the FDA for further testing. The agency is extending its testing to ranitidine oral solutions, and it has begun testing samples of other H2 blockers and proton-pump inhibitors for the impurities.

The NIH's National Institute on Aging launched two new research centers to diversify and reinvigorate the Alzheimer's disease drug development pipeline. With funding expected to total more than $73 million over the next five years, the Alzheimer Centers for the Discovery of New Medicines will provide added infrastructure for developing the research tools and technologies needed to validate and advance the next generation of drug targets for Alzheimer's. The data, research methodologies, and computational and experimental tools developed by the centers will be freely available to the broader research community for use in drug discovery and in research to better understand the biology of the disease. The Open Drug Discovery Center for Alzheimer's Disease (AMP-AD) will be led by Allan Levey at Emory University in Atlanta, Lara Mangravite at Sage Bionetworks in Seattle and Aled Edwards, who is with the Structural Genomics Consortium, which has research sites in North Carolina, Toronto and Oxford, U.K. Leveraging the data and results from the AMP-AD program, the team will develop a series of new therapeutic hypotheses centered around a prioritized set of novel targets, according to the NIH. The Indiana University School of Medicine Alzheimer's Disease Drug Discovery center will bridge the target discovery work done by the AMP-AD program with newly discovered molecules that will be studied for disease-modifying potential in Alzheimer's animal models. The researchers will create drug targets representing new therapeutic hypotheses, with a focus on immune pathways.

The NIH awarded $20 million to fund five additional Research Evaluation and Commercialization Hubs (REACH), expanding the national network of proof-of-concept centers that advance promising technologies from academia to small businesses, translating biomedical innovations into commercially viable diagnostics, devices, drugs and development tools. The new hubs are the Kentucky Network for Innovation & Commercialization, Rutgers Optimizes Innovation Program, Midwest Biomedical Accelerator Consortium, Colorado Anschutz Medical Campus REACH Hub and Washington Entrepreneurial Research Evaluation and Commercialization Hub. In addition to the NIH funding, each hub secured nonfederal matching funds and developed partnerships with regional life science and economic development organizations. The hubs scout for biomedical projects and provide funding, milestone-driven project management support and entrepreneurial education to help innovators transform laboratory discoveries into viable health care solutions.

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