Although Gilead’s recent quarterly results were worse than expected, one strong ray of light was remdesivir thanks to the fact that the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) on May 1, 2020 for use against COVID-19. This was made possible based on an “adaptive trial,” where the National Institute of Allergy and Infectious Diseases (NIAID) allowed an unprecedented change in trial endpoint, leading to the FDA action. After the trial, Dr. Fauci declared a “new standard of care,” while also noting it was no “knock out drug.” What was the result? Gilead forecasts sales totals for 2020 to be between $23 billion and $25 billion (up from the range of $21.8 billion to $22.2 billion); and importantly, star analyst Michael Yee with Jefferies reports that this implies up to $1 to $3 billion of remdesivir sales alone. TrialSite also surveys alternative therapies (other than vaccines) under investigation targeting COVID-19. As it turns out, there is a lot more going on than many in nations such as the United States are aware, as major media outlets are careful about what investigational therapies get airtime.
To date, in the United States, formal medical establishments (and the government) acknowledge only two drugs so far, remdesivir and the generic steroid dexamethasone, that have shown in rigorous clinical trials to help patients with COVID-19. TrialSite address more on this below.
Overall Weaker Sales
Generally, Gilead experienced weaker sales thanks to a decline in demand for its hepatitis C drugs and flagship HIV treatments during the COVID-19 pandemic lockdowns. However, as economies open back up, Gilead reports it expects those products to pick up again. Should no more lockdowns occur, Gilead is prime for a robust 2021.
Changing the Goal Post & Opening the Door for EUA Commercialization
In collaboration with the National Institute of Allergy and Infectious Diseases (NIAD) led by Dr. Anthony Fauci and the U.S. Food and Drug Administration, the TrialSite reported that Gilead’s pivotal Phase 3 remdesivir trial actually did not meet its initial primary endpoint: a reduction in COVID-19 death rates. So, in an unprecedented move toward the end of the trial, the government allowed the prominent industry sponsor to actually change the endpoint to center on reduction in duration of hospitalization. As it turns out, Remdesivir reduced the number of hospitalized days from about 15 to 11.
The Conscience of Fauci: ‘Not a Knockout Drug’
Dr. Fauci declared back in May upon the FDA EUA that remdesivir is the “new standard of care.” As the TrialSite has noted:
Hence, on the one hand, Dr. Fauci’s signal to the medical establishment that remdesivir is a “standard of care” based on the evidence-and hence immediately thereafter the U.S. Food and Drug Administration (FDA) granted emergency use authorization for the new “standard of care” and hence opening up the sales of the drug. But seemingly wanting to get the other side out there—perhaps to clear the conscious—the head of the National Institute of Allergy and Infectious Diseases (NIAID) noted, as reported in the Washington Post “that remdesivir is not a knockout drug that will change the trajectory of the coronavirus pandemic.”
Commercialization based on EUA
With the NIAID and FDA ensuring a greenlight, Remdesivir’s commercialization commenced full throttle. The drug was granted emergency use authorization (EUA) by the FDA in May. The drug still doesn’t have full approval but that doesn’t matter, as the EUA has opened up the spigot for robust investigational product sales. Therefore, the company was able to capitalize on a confluence of forces from the pandemic itself, to previous research into Ebola, to a healthy relationship with NIAID to real investment the company makes on a daily basis to fund drug development. Although the drug can only be used on hospitalized patients by infusion, demand now outstrips supply in many parts of the world. The company’s sales team has been implementing partnerships with other generic companies as well to distribute in low-to-middle income countries. This will lead to between $1 billion and $3 billion in 2020 alone.
Gilead reports it expects to produce 2 million or more remdesivir treatment courses cumulatively in 2020, and its revenue outlook expected sales of up to 1.5 million courses this year. Of course the price is far lower for the deals the company is doing in low-to-middle-income countries, but when added up its amounts to sales between $1 billion to $3 billion.
Moreover, the company is working furiously to develop an inhaled version of remdesivir. In fact, it launched a clinical trial testing to see the efficacy of delivering the antiviral drug to the lung tissue. To further monetize the COVID-19 market, Gilead will also investigate use of the drug in earlier-stage COVID-19 patients.
The ACTT-2 Study
Additionally, the NIAID is sponsoring a study investigating the use of remdesivir in combination with Eli Lilly’s Olumiant, an arthritis drug. Results are expected this month. This study was initiated in May and is schedule to complete in August. Called the ACTT-2 study, it evaluates the combination of baricitinib (Olumiant) and remdesivir compared to remdesivir alone. Participating subjects are assessed while hospitalized. The study’s primary endpoint, time to discovery (from Day 1 to Day 29), is defined as the first day of which the subject satisfied either 1) not hospitalized, no limitations on activities; 2) not hospitalized, limitation on activities and/or requiring home oxygen; and 3) hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care. A number of secondary endpoints are targeted as well. The study is being conducted at 71 centers in the U.S. and beyond.
What else is out there?
A number of other drugs showed promise but are not well accepted by the establishment even for investigational purposes.
Although some studies continue to show positive elements for the anti-malaria drug hydroxychloroquine, it’s essentially political taboo to discuss (and there are studies with negative results). Recent positive results, such as from the Ford Health System study, evidence that hydroxychloroquine may reduce COVID-19 death rate but are not considered sufficient by most of the medical establishment at this point. Other studies, such as the recent World Health Organization (WHO) initiative, found the drug didn’t help.
Antiviral Favipiravir (Avigan) has been approved in Russia, China and India; and there are studies in the U.S. but the mainstream press rarely mentions this antiviral therapy. Stanford has a study now to investigate favipiravir in COVID-19 patients. The U.S. Department of Defense spent half a decade and $200 million studying this drug for viruses such as the coronavirus.
Merck is seeking to compete with remdesivir with its EIDD-2801: an experimental antiviral therapy. Regeneron has announced clinical trials for its powerful combination monoclonal antibody known as REGN-COV2 (note Regeneron secured $450 million of public money from this effort). Dr. Fauci and NIAID are upbeat about this advanced investigational therapy.
Recently, Actemra (tocilizumab), a disease-modifying anti-rheumatic drug (DMARD) approved for rheumatoid arthritis and juvenile idiopathic arthritis (both inflammatory diseases), failed in a COVID-19 clinical trial, although India has approved the drug and reports robust sales. Kevzara (sarilumab) failed to make a difference for COVID-19 patients as well. Both of these block interleukin-6 (IL-6), a protein active in natural immune responses. IL-6 typically tells other cells to activate the immune system, however too much of this can lead to danger such as the cytokine storm, associated with severe cases of acute respiratory distress syndrome (ARDS) and COVID-19.
The promise of IL-6 inhibitors was that those COVID-19 patients at risk for the cytokine storm could potentially benefit by inhibiting IL-6 and hence calming down the immune system. Thus far, the results aren’t great. Other immunotherapies under investigation include Calquence (acalabrutinib), Xeljanz (tofacitinib), Jakafi (ruxolitinib), Olumiant (baricitinib), Kineret (anakinra), Ilaris (canakinumab), Otezla (apremilast), and Mavrilimumab.
Other antivirals under study include umifenovir (Arbidol), a flu medication used outside of America, however in a study in China versus favipiravir the latter was superior to the former. In another study, umifenovir showed no benefit to COVID-19 patients and appeared superior to Kaletra at helping COVID-19 patents clear the virus. In one small study out of China involving 50 subjects, umifenovir appeared to help the COVID-19 patients clear the virus by 14 days while fifty percent of those who took Kaletra still had the virus.
Another antiviral, Galidesivir, has some potential. The antiviral drug, an adenosine analog, is under development by BioCryst Pharmaceuticals with funding from the NIAID. Originally intended for hepatitis C, it is under investigation for filovirus infections such as Ebola virus and Marburg virus. It demonstrates a broad-spectrum antiviral effectiveness against a range of other RNA virus families. It is now being investigated in a randomized, double-blind, placebo-controlled clinical trial to treat COVID-19. In collaboration with NIAID, the sponsor commenced the Phase 1 clinical trial to test in COVID-19 patients in Brazil.
What about interferon?
TrialSite reported that interferons occur naturally in the body, and some scientists are wondering if interferons could stop COVID-19 before it takes hold. Several interferons have been approved by the FDA for decades, and their use includes cancer and hepatitis. One recent study in China revealed that the use of interferon could prevent infections. It has not been peer reviewed. The so-called “Cuban interferon” has been in demand as a COVID treatment, and international researchers have suggested that interferon (IFN)a2b could be superior to Remdesivir in treating COVID-19.
Sanford Burnham Prebys Identified Drugs Targeting COVID-19
The San Diego, CA area research institute discovered 21 actual drugs that at effective concentrations could not only be safe but could possibly treat COVID-19. The top candidates include Clofazimine, Hanangchin A, Apilimod and ONO 5334. The TrialSite reported recently that Yale Medicine has partnered with AI Biotherapeutics to investigate whether in fact Apilimod, a first-in-class highly selective kinase inhibitor evidencing antiviral activity against several isolates of SARS-CoV-2, can inhibit the novel coronavirus.
A medication used for gout, it works in a number of ways, including activating anti-inflammatory processes and impeding cells involved in inflammation. Some investigators believe it could work similarly to tocilizumab in COVID-19 patients and hence be helpful in combatting conditions such as the cytokine storm. The TrialSite recently reported on the Montreal Heart Institute Colchicine study.
Observational data from around the word exhibits promise that this antiparasitic drug can reduce the COVID-19 virus duration by as much as 50%. What is the real world evidence the TrialSite has accumulated? This includes interviews with the President of Grupo Rescue health system in Dominican Republic; discussions with Dr. Tarek Alam of the Bangladesh Medical College; ongoing discussions with Dr. Jean-Jacques Rajter of Broward County Health; ongoing clinical trials announced from Israel and India to Mexico, Argentina and Brazil to University of Kentucky and Johns Hopkins University, to the issuance of approvals in Peru and at least regionally in Bolivia. Carlos Chaccour is adamant that these counties have approved the drug based on one suspect Surgisphere paper but while the TrialSite completely agrees with Dr. Chaccour that Surgisphere is more than suspect, TrialSite interviews in Peru and Bolivia counter the claim that approvals and/or use of Ivermectin is only due to this suspect paper. Still needed for Ivermectin’s acceptance in wealthy countries: evidence from robust randomized controlled trials.
In addition to the recent breakthrough with dexamethasone, TrialSite reported on the STOIC trial involving Queensland University of Technology and Oxford University centered on assessing the effectiveness of inhalers as possible treatment for COVID-19. The investigators working out of Churchill Hospital evaluate inhaled corticosteroid therapy compared to the standard of care. Note, our coverage of a West Texas doctor (Dr. Bartlett) created a stir—he reported success with inhaled steroid Budesonide, calling it a “silver bullet” for treating COVID-19.
In another good ending, Dr. Thomas Pitts saved the life of a COVID-19 patient on the verge of death using an EUA to access Eculizumab. Could this medication save more lives?