diaTribe Presents at the FDA – A Public Hearing About the Challenges of CVOTs and Bringing Drugs to Market

Twitter summary: dT presents at @US_FDA on interim results for CVOT trials in #diabetes & why we can’t delay innovation

In 2008, the FDA mandated that companies demonstrate that new diabetes drugs don’t carry an excessive risk of heart disease or strokes (‘cardiovascular’ risk) – see our 2009 interview with FDA patient representative Rebecca Killion who had strong opinions about that vote. Since cardiovascular events occur infrequently – especially in trials, where patients are under close supervision – companies must as a result of guidance stemming from the 2008 Avandia saga (see our interview with Dr. Steven Nissen from 2007 for more on this) conduct long and expensive cardiovascular outcomes trials (known as “CVOTs”) to demonstrate that their drugs are safe. While the additional data is very important for understand long-term side effects and safety profile, it adds time and expense to bring new drugs to market. Companies have the option to speed up this process by revealing data from the trial before it ends, although this strategy could have a downside – in some cases, this action could compromise the integrity of the trial, since results are supposed to blinded right until the end and some worry that if patients find out results, they may leave the trial for various reasons. On August 11, the drug division of the FDA held a public hearing to discuss this issue, and the diaTribe and Close Concerns teams presented on behalf of patients.

The day featured public presentations and discussion from a range of experts, including the ADA’s Dr. Robert Ratner, who spoke most compellingly on behalf of patients, in our view (he was a very respected long-time researcher before taking the reigns at the ADA running the science side). Some talks, including ours as well as Dr. Ratner’s, centered on ways the FDA should balance innovation with the need to gather long-term safety data on new drugs. diaTribe editor-in-chief Kelly Close presented on the challenges of revealing early results from CVOTs, as well as the consequences of the CVOT requirement on innovation (e.g., multi-year delays on Novo Nordisk’s insulin degludec and potentially transformational combo insulin/GLP-1 Xultophy, fewer funds going into the field, etc.).

Speaking on behalf of diaTribe and dQ&A, Manu Venkat presented a dQ&A survey of 5,300 patients, sharing their perspectives on biasing trial results when early data is released – you can view both of their presentations by clicking here (Kelly) and here (Manu). (A sidenote – if you do not take dQ&A surveys and want to get your voice heard, please write nida@d-qa.com.) The issue is unquestionably complex, and a number of presentations focused on the need for clearer FDA guidelines on appropriate and optimal trial design and data disclosure. Notably, the FDA’s Dr. Lisa LaVange expressed concern that CVOT safety requirements could drive companies away from diabetes research and innovation (indeed, the requirement has already driven companies like BMS out of diabetes in addition to significantly raising the bar on taking drugs through the approval process). The outcome of the hearing is unclear, and we’ll be staying very tuned to see what happens; we will report back to you pronto on this. To learn more about CVOTs and how they influence drug development, please read our letter from the editor on the FDA public hearing. – NL