WALTHAM, Mass.– The recently announced benefits of fluvoxamine, an inexpensive drug currently approved as an antidepressant, for treating COVID-19, were confirmed thanks to a platform research study, the TOGETHER Trial, which included key design and implementation contributions from Cytel researchers. According to research study data, Fluvoxamine was found to reduce the number of COVID-19 patients ending up in hospital by approximately 30 percent.
The results, while not peer reviewed, were recently presented before the US National Institutes of Health and the World Health Organization by Cytel Principal Scientist and TOGETHER Trial co-Principal Investigator, Professor Edward Mills of McMaster University.
Speaking of the fluvoxamine results, Mills said, “This is a massive finding of benefit to public health. There is no other treatment for early COVID that has been shown to prevent the need for hospitalization.”
Since the beginning of the pandemic, Mills has been committed to finding therapies for COVID-19 that are widely and equitably accessible to all, including those who live in low- and middle-income nations. The vaccines and many of the therapies currently proposed, are only available in wealthier nations, leaving less well-off nations scrambling to protect their populations. Mills works with a global network of health specialists aiming to address this challenge, and platform trials have been a significant tool in this process.
Platform trials, such as those used to test fluvoxamine, allow multiple therapies to be tested using a single study design with a shared control arm. This reduces costs and accelerates the overall process of establishing efficacy by several years, and ensures more patients are enrolled into arms containing newer medicines. Although difficult to administer, platform trials are ideal for use during a public health emergency, when rapidly identifying cost-effective new therapies is a priority.
The TOGETHER Trial is testing well-known drugs for benefits in the treatment of COVID-19. In addition to fluvoxamine, others have included hydroxychloroquine, lopinavir/ritonavir, metformin, ivermectin, Peg-interferon-Lambda, and doxazosin. Each drug is well-known to the medical community, with established safety profiles for doctors to follow, is widely available, and is relatively inexpensive to produce. Before the positive findings about fluvoxamine had been announced, hydroxychloroquine, lopinavir/ritonavir, and metformin had been dropped from the study after early results failed to find a substantial benefit. Initial testing of ivermectin found no positive benefits, however a second test with a different dosage is still awaiting results.
According to Dr. Kyle Wathen, VP of Scientific Strategy and Innovation at Cytel, “Platform trials are not only efficient at identifying therapies that work, they tend to quickly eliminate poorly performing therapies, making it a double win.”
Dr. Wathen is well known for his work in platform trials having helped design several platform trials previously and his contributions and help in designing the I-SPY 2 trial, a platform trial that transformed breast cancer research. He now leads the Master Protocols group at Cytel which combines studies of platform trial designs with other designs like basket and umbrella trials.
Using conventional research study designs, the seven therapies in the TOGETHER Trial would each require their own control arm, and possibly take place concurrently but with more investment in resources, time and other considerations. The TOGETHER Trial’s design has the additional benefit of accumulating and processing data more quickly, and comparing complex evidence more easily, even while simultaneously ensuring high scientific rigor.
Besides being much cheaper to administer, the use of a platform trial resulted in a dramatically shorter research study duration than would have been needed to run seven distinct studies. Faster research studies make it much more likely that a life-saving therapy can be identified from a range of inexpensive, well-known medications.
Says Dr. Wathen, “By sharing the standard of care arm of the research study design, the cost of testing each drug is slashed importantly. Plus, it is easier to compare different therapies to each other to see which are the most effective, because they share a common research study protocol.”
Sharing the control arms provides benefits, but it also creates technical complexity, generates organizational challenges, and increases demands for specialist expertise. Because of these factors, previous adaptive platform trials have mostly been restricted to the World Health Organization, the National Institute of Health, and other globally leading health organizations with access to extensive resources.
The TOGETHER TRIAL may also open the door for platform trials to become a much more widespread research study design. Through Cytel’s contributions, this breakthrough demonstrates that this global health tool is now within reach of institutions and governments who previously lacked the resources to run platform trials on their own.
Cytel CEO Joshua Schultz says: “For thirty years Cytel has been at the forefront of innovation in clinical research. We are proud to have successfully designed and implemented a platform trial with the potential to help people around the world struggling with the lingering COVID-19 pandemic. We are hopeful that the TOGETHER Trial will continue to identify beneficial therapies, and that the use of sophisticated approaches to designing and executing research studies will continue to expand.”