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Hedging the vaccine bet
It's a race that the public, government, health officials and Wall Street are watching intently, happening in labs worldwide, where researchers work, day and night, to develop coronavirus vaccines. By the World Health Organization's current count, 44 vaccines are undergoing clinical trials, with 154 candidates in preclinical development. The work happening in vaccine development is inspiring and groundbreaking. Operation Warp Speed, an inter-agency U.S. government program, has invested previously unimaginable sums in vaccine development, manufacturing and distribution.
Newer ideas, like vaccines based on RNA or DNA, are being seriously pursued. Many of the best drug development teams at the largest pharma companies have been assigned to vaccine programs. Several developmental vaccines have reached stage 3 trials and there is well-founded optimism that one or more will eventually be approved.
But despite all the positive news on this front, are we betting too much on vaccines? From my ringside seat in designing smarter, faster drug development programs, it is obvious that it is nearly impossible to fully predict any individual vaccine candidate's timing or success before large trials are finished and analyzed to understand safety and efficacy fully. Human biology and the variations in human populations are complicated, so we test medicines using human trials.
However, many people need treatment for COVID now and the timing and the effectiveness of the coming vaccines are simply uncertain. It's wise to hedge our bet and continue to find therapies that work to treat COVID.
Developing completely new drugs to combat COVID may be theoretically possible, but we don't have time. That's why much of the worldwide effort has gone into testing existing drugs that are already-on-the-market to see if they help with COVID. Some, like steroids and remdesivir, have been shown to have some useful effect on patients. Many others are known to act against the virus in a test tube but have not been effective enough at safe dosing levels to be recommended as treatments. What hasn't been extensively trialed - but should be - are combinations of drugs.
The idea is simple - even if no individual drug can wipe out the virus, if we hit it from enough different directions simultaneously, we have a chance to arrest its progress in individuals and reduce its severity, increasing seriously ill patients' chances of survival. It's a potentially effective approach. Yet, even though trials of monotherapies have largely proven to be ineffective, only 13 percent of clinical trials today are devoted to these combination therapies. We could and should be doing more.
Several potential combinations are nearing the end of testing with encouraging results. The viral life cycle of COVID-19 supplies a framework to guide the selection of the right therapeutic combinations. In current trials, particular drug candidates are impacting key points in the virus's life cycle.
For example, remdesivir accelerates median recovery time in patients hospitalized with lower respiratory tract impact from 15 to 11 days. A combination of interferon-beta-1b with ribavirin and lopinavir/ritonavir decreases both productive cell death and virion release and reduces viral shedding by five days vs. lopinavir/ritonavir alone. Adding convalescent plasma or monoclonal antibodies to remdesivir or lopinavir/ritonavir and interferon targets three parts of the viral life cycle - virion release, productive cell death and target cell infection- at the same time.
Additionally, a preliminary study of the hepatitis C drugs sofosbuvir and daclatasvir in combination showed that after 14 days, 29 patients (88 percent ) in the group receiving the cocktail reached clinical recovery compared with 22 (67 percent ) in the control group. Combination therapy patients experienced a shorter hospital stay duration and a median time to discharge compared with the control group (6 vs. 8 days and 6 vs. 11 days, respectively), with no adverse events reported. These results should be confirmed with a larger study and, if favorable, the drugs could be quickly made available for as little as $7 per 14-day treatment course.
These are extremely promising findings. Harnessing combination therapies' incremental impacts will fill the gap until vaccines are successfully developed, tested, approved and manufactured at a scale that can stop this pandemic.
To meet the immediate needs and provide treatment for acute cases until and even after, a vaccine is widely available; combination therapy represents the best chance we have of fighting serious COVID-19 cases globally. While all effort should be made in vaccine development, we must not forget the cocktail approach's value. We should devote the resources necessary to test these therapies and use them to treat those who need them now.
William F. Feehery, Ph.D., MBA, is CEO of Certara, an industry leader in applying quantitative decision-making frameworks across the drug development life cycle and was president of DuPont Industrial Biosciences (2013-2019). A Churchill Scholar at Cambridge University and recipient of a National Science Foundation Fellowship, his doctorate involved developing software and mathematical methods for modeling complex systems.