Our nation finds itself still experiencing a staggering number of new coronavirus cases and deaths each day. With competing voices and opinions — even among our leaders — about how best to manage this crisis, all hope seems to rest on a safe and effective vaccine. We are so taken with the idea of a vaccine because it holds forth the promise that we can someday return to our normal lives. Our government has invested heavily in that promise.
While efforts to develop a vaccine are important and necessary, we must recognize a vaccine will not be a panacea and invest in a concurrent strategy to ensure effective COVID-19 therapeutics are available to those for whom a vaccine may not be available or effective. And as the president of the United States himself, this month received treatment for COVID-19 with therapeutics; we are reminded that there remains an immediate and urgent need for a proven, near-term solution for all Americans. Before a vaccine is proven safe, effective and is widely available, the need for effective therapeutics, and production of those therapeutics at scale, is critical.
Two therapeutics have proven effective in randomized controlled clinical trials, the gold standard of drug development. Remdesivir acts directly on viral replication and has been shown to reduce the number of days patients spend in the hospital. Dexamethasone acts by suppressing the immune response and has demonstrated the ability to reduce death, although previously ventilated patients benefitted most.
These positive clinical results offer a few initial pieces of the puzzle and suggest that we can rationally design a therapeutic cocktail by targeting both the virus and the overactive immune response with the expectation of improving results. This strategy has proven effective for other viral diseases such as HIV and Hepatitis C.
The National Institutes of Health (NIH) is already applying this cocktail approach by studying the combination of remdesivir (antiviral) with baricitinib (anti-inflammatory), with results recently released. The NIH is also exploring the combination of remdesivir (antiviral) with lenzilumab, another anti-inflammatory agent that acts by targeting an immune-signaling protein, GM-CSF, thought to be the “master controller of the immune system,” as part of its ACTIV-5/“Big Effect Trial” (BET).
GM-CSF is elevated in severe and critical COVID-19 patients and stimulates the production of signaling proteins known as cytokines, which often result in hyperinflammation, or “cytokine storm.” Anti-cytokine therapeutics such as lenzilumab that act on this master controller target multiple inflammatory proteins and may be able to quell the cytokine storm more effectively than agents targeting a single cytokine.
Promising results were recently published in a peer-reviewed Mayo Clinic case-control study. Treatment with lenzilumab was associated with an 80 percent reduction in the relative risk of ventilation and death. If the therapeutic combinations being studied by NIH are shown to be effective, we may be able to begin re-setting our societal response to the pandemic even before a vaccine is available.
As the phase 3 trials for these investigational COVID-19 therapeutics advance toward anticipated FDA approval in 2020, the next major challenge will be getting these medicines to patients. Small companies like Humanigen are doing everything possible to secure manufacturing capacity, but without government agencies’ support, the bottlenecks in manufacturing capacity and consumables will not be resolved. Even if these therapies receive FDA approvals, patients could be denied access due to a shortage of supply, forcing hospitals and doctors to ration highly effective therapies.
Shoring up manufacturing for the 250,000 Americans projected to require treatment this winter is minuscule compared to the manufacturing capacity required to develop hundreds of millions of doses to vaccinate Americans. Our government has already allocated billions to support vaccine development. Can’t we invest a fraction more to solve capacity and supply issues for the most promising therapeutics and ensure Americans have access to effective treatments for this devastating disease?
We can all agree that developing a safe and effective vaccine is a worthy goal. However, a singularly focused strategy on vaccines comes with substantial risk. The potential for therapeutics to address the virus this winter and beyond is easily achievable. Too many American lives are at stake for our public health leaders and politicians to place all their bets on red.
Dale Chappell is the Chief Scientific Officer at Humanigen, a former HHMI Fellow, National Cancer Institute and an expert in T-cell therapy, GM-CSF and immunology pathways.