As anticipation mounts over the prospects for an experimental Gilead Sciences (GILD) drug to combat the novel coronavirus, two Wall Street analysts suggested it remains uncertain whether the antiviral therapy will be successful after assessing a new paper that examined a dozen U.S. patients.
The paper, published on a preprint server without peer review, described the epidemiology, clinical course, and viral characteristics of the first 12 U.S. patients with Covid-19, only three of whom were treated with remdesivir, which was developed to treat the Ebola virus but shelved after proving less effective than other drugs during testing. The analysis was conducted by the Centers for Disease Control and Prevention Covid-19 response team.
The team looked at patients with mild to moderately severe illness, which was detected early, and the findings indicated that “the window for diagnosis is long” and hospitalized patients showed signs of worsening in the second week after illness began. But RBC Capital Markets analysts examined individual patient data and decided the Gilead drug showed mixed results, at best.
“Based on our review of the clinical and virological courses, we believe remdesivir’s contribution to efficacy remains unclear, and with a side-effect profile that may not be completely benign,” the RBC analysts wrote in a note to investors. “We continue to see a less than 50/50 possibility that the drug is ultimately proven effective.”
More specifically, they maintained there was not a “clear temporal association” between treating patients with remdesivir and improvements in oxygen requirements, fever, and viral results, compared with hospitalized patients who did not receive the investigational drug. The analysts also noted that remdesivir patients experienced nausea, vomiting, rectal bleeding, and elevated liver enzymes.
As the pandemic spreads, a race is underway to develop therapies and vaccines, but also cull existing treatments for ways to combat the virus. The Gilead drug, which was revived recently, is high on the list and testing has begun in the U.S. and China. The drug maker, which distributed the drug on a compassionate use basis to several hundred patients, expects to start its own late-stage trials this month.
Consequently, every twist and turn involving each product and each test will be closely scrutinized for signs of effectiveness. Even preliminary findings will be picked through for clues, given that countless lives depend on such outcomes. The Covid-19 response team, which includes public health officials from around the U.S., noted the paper was not peer-reviewed and research has not yet been evaluated.
Nonetheless, the RBC analysts wrote there is “good news and bad news” about the course of the disease. Besides side effects, several patients were hospitalized despite being under 60 years old and with limited comorbidities. Several also worsened in the second week of treatment, suggesting prolonged monitoring and management will be required, they wrote.
On the other hand, the study authors concluded that “the overall clinical course appears more favorable than what was observed in China, for patients in the U.S.” Notably, 42% did not require hospitalization. But the analysts cautioned that it is “unclear whether this represents a different level of medical care or an evolving viral profile.”
Some qualifiers are worth noting. Again, the analysis was not peer reviewed. Under the circumstances, there is likely to be a much lower bar than usual for various side effects. And as the analysts acknowledged, interpretation of the findings is “confounded by multiple other medications, including steroids and antibiotics, given to many of these patients.”
Moreover, the Gilead drug was typically given to patients as they worsened, so it remains possible the drug prevented them from taking an even worse turn. Finally, the analysts noted that remdesivir was given to the patients at a later stage of illness than in the clinical trials, suggesting the therapy can yield a better outcome if administered sooner rather than later.
“The small sample size and mixed results highlight the difficulty in obtaining a clear picture of efficacy,” the analysts conceded.
[UPDATE: Later, a Gilead spokeswoman wrote us that remdesivir is being assessed in multiple clinical trials globally in order to evaluate its safety and efficacy in treating COVID-19… We also have safety information from trials… in Ebola.” In Phase 1 single and repeated dose safety and pharmacokinetic studies in more than 80 healthy humans, the drug exhibited “predictable dose-proportional pharmacokinetics with no observed serious adverse effects. Transient low-grade elevations in liver transaminases were observed during the Phase 1 studies in some participants – the clinical significance of these laboratory changes is not known.
“Clinical trials have also been conducted in Ebola survivors in West Africa, and in patients with acute Ebola virus disease in the Democratic Republic of Congo. As of January 18, 2020, more than 500 individuals have received at least a single IV dose of remdesivir, of which 400 were patients in the DRC with acute Ebola and were treated either in a Phase 2/3 trial or in emergency investigatioanl protocols, or MEORI. In these studies, no significant adverse events or laboratory abnormalities were attributed to remdesivir by study investigators.”]