Drug kills virus in test tube, FDA chief reports

The Food and Drug Administration commissioner indicated yesterday that doctors can use chloroquine or hydroxychloroquine in treating Covid-19 though he said more data are needed to assure that the drugs are effective.

Dr. Stephen Hahn, the FDA chief, spoke with Tucker Carlson of Fox News.

"We do have data from other countries we are looking at, and specifically one trial from France which suggests we might have some benefit for hydroxychloroquine or chloroquine against the Covid-19 disease," Hahn said.

"We also have data from test-tube experiments that it does have activity against the virus," Hahn continued. "That being said, we need more safety and more efficacy data, particularly the efficacy side of this drug, to make a final determination about the effectiveness."

He said that, if as a doctor he were hearing a patient ask about the drug, he would want to know that its use was safe for that particular patient before prescribing it. Both chloroquine and hydroxychloroquine have "known safety profiles with the main concerns being cardiotoxicity" with prolonged use in patients with hepatic or renal dysfunction and immunosuppression but have been reportedly well-tolerated in Covid-19 patients, experts report.

But, he said that under Centers for Disease Control guidelines, the drug is "available for that purpose." CDC guidelines on chloroquine were posted within the last two days.

https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html

According to CDC guidance for clinicians, there are no FDA-approved drugs specifically targeting Covid-19. An array of drugs used for other purposes as well as some experimental drugs are being studied in several hundred clinical trials under way across the globe.  The CDC spotlighted the drugs chloroquine and hydroxychloroquine, which are used in the United States for arthritis and other purposes, and  the experimental drug remdesivir.

The following information comes from the CDC.

Hydroxychloroquine and Chloroquine

Hydroxychloroquine and chloroquine are oral prescription drugs that have been used for treatment of malaria and certain inflammatory conditions. Chloroquine has been used for malaria treatment and chemoprophylaxis, and hydroxychloroquine is used for treatment of rheumatoid arthritis, systemic lupus erythematosus and porphyria cutanea tarda.

Both drugs have in-vitro activity against SARS-CoV, SARS-CoV-2, and other coronaviruses, with hydroxychloroquine having relatively higher potency against SARS-CoV-2 . A study in China reported that chloroquine treatment of COVID-19 patients had clinical and virologic benefit versus a comparison group, and chloroquine was added as a recommended antiviral for treatment of COVID-19 in China.  Based upon limited in-vitro and anecdotal data, chloroquine or hydroxychloroquine are currently recommended for treatment of hospitalized COVID-19 patients in several countries.

Both chloroquine and hydroxychloroquine have known safety profiles with the main concerns being cardiotoxicity (prolonged QT syndrome) with prolonged use in patients with hepatic or renal dysfunction and immunosuppression but have been reportedly well-tolerated in COVID-19 patients.

Due to higher in-vitro activity against SARS-CoV-2 and its wider availability in the United States compared with chloroquine, hydroxychloroquine has been administered to hospitalized COVID-19 patients on an uncontrolled basis in multiple countries, including in the United States. One small study reported that hydroxychloroquine alone or in combination with azithromycin reduced detection of SARS-CoV-2 RNA in upper respiratory tract specimens compared with a non-randomized control group but did not assess clinical benefit.

Hydroxychloroquine and azithromycin are associated with QT prolongation and caution is advised when considering these drugs in patients with chronic medical conditions (e.g. renal failure, hepatic disease) or who are receiving medications that might interact to cause arrythmias.

Hydroxychloroquine is currently under investigation in clinical trials for pre-exposure or post-exposure prophylaxis of SARS-CoV-2 infection, and treatment of patients with mild, moderate, and severe COVID-19. In the United States, several clinical trials of hydroxychloroquine for prophylaxis or treatment of SARS-CoV-2 infection are planned or will be enrolling soon.  More information on trials can be found at:  https://clinicaltrials.gov/external icon.

There are no currently available data from Randomized Clinical Trials (RCTs) to inform clinical guidance on the use, dosing, or duration of hydroxychloroquine for prophylaxis or treatment of SARS-CoV-2 infection.  Although optimal dosing and duration of hydroxychloroquine for treatment of COVID-19 are unknown, some U.S. clinicians have reported anecdotally different hydroxychloroquine dosing such as: 400mg BID on day one, then daily for 5 days; 400 mg BID on day one, then 200mg BID for 4 days; 600 mg BID on day one, then 400mg daily on days 2-5.

Remdesivir

Remdesivir is an investigational intravenous drug with broad antiviral activity that inhibits viral replication through premature termination of RNA transcription and has in-vitro activity against SARS-CoV-2 and in-vitro and in-vivo activity against related betacoronaviruses.

There are currently four options for obtaining remdesivir for treatment of hospitalized patients with COVID-19 and pneumonia in the United States:

A National Institutes of Health (NIH)-sponsored adaptive double-blinded, placebo-controlled trial of remdesivir versus placebo in COVID-19 patients with pneumonia and hypoxia is enrolling non-pregnant persons aged 18 years and older with oxygen saturation of ≤94% on room air or requiring supplemental oxygen or mechanical ventilation.

https://clinicaltrials.gov/ct2/show/NCT04280705

Exclusion criteria include alanine aminotransaminase or aspartate aminotransaminase levels >5 times the upper limit of normal, stage 4 severe chronic kidney disease or a requirement for dialysis (i.e., estimated glomerular filtration rate (eGFR) <30); Two phase 3 randomized open-label trials of remdesivir (5-days versus 10-days versus standard of care) are open to enrollment in persons aged 18 years and older with COVID-19, radiographic evidence of pneumonia and oxygen saturation of ≤94% on room air (severe disease).

https://clinicaltrials.gov/ct2/show/NCT04292899

or >94% on room air (moderate disease).

https://clinicaltrials.gov/ct2/show/NCT04292730

Exclusion criteria include alanine aminotransaminase or aspartate aminotransaminase levels >5 times the upper limit of normal, participation in another clinical trial of an experimental treatment for COVID-19, requirement for mechanical ventilation, or creatinine clearance <50 mL/min; and Finally, in areas without clinical trials, COVID-19 patients in the United States and other countries have been treated with remdesivir on an uncontrolled compassionate use basis. The manufacturer is currently transitioning the provision of emergency access to remdesivir from individual compassionate use requests to an expanded access program.  The expanded access program for the United States is under rapid development. Further information is available at:

https://rdvcu.gilead.com/

Other Drugs

Lopinavir-ritonavir did not show promise for treatment of hospitalized COVID-19 patients with pneumonia in a recent clinical trial in China. This trial was underpowered, and lopinavir-ritonavir is under investigation in a World Health Organization study.

Several other drugs are under investigation in clinical trials or are being considered for clinical trials of prophylaxis or treatment of COVID-19 in the United States and worldwide. Information on registered clinical trials for COVID-19 in the United States is available at:

https://clinicaltrials.gov/