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J&J statement: Lack of evidence to support use of darunavir-based treatments for SARS-CoV-2:
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Download the PDF here
https://www.jnj.com/lack-of-evidence-to-support-darunavir-based-hiv-treatments-for-coronavirus
Results from a single center, open label, randomized, and controlled trial conducted at Shanghai Public Health Clinical Center (SPHCC) of darunavir and cobicistat (DRV/c) in treating laboratory-confirmed 30 COVID-19 patients showed that DRV/c was not effective. The in-vitro antiviral activity of DRV against SARS-CoV-2 was assessed. DRV showed no activity against SARS-CoV-2 at clinically relevant concentrations (EC50 >100 μM). These data do not support the use of DRV for treatment of COVID-19. Janssen is leading collaborative efforts to screen compounds in discovery and development within our organization and across the broader pharmaceutical industry to accelerate the development of therapies. We have also initiated a high priority project to develop a SARS-CoV-2 vaccine candidate leveraging our AdVac and PER.C6 technologies.
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study:
This study demonstrated that DRV showed no in vitro antiviral activity
against SARS-CoV-2 at clinically relevant concentrations.
In this study, remdesivir demonstrated activity against SARS-CoV-2 with an EC50 of 0.38 μM,
which is in line with the earlier reported remdesivir EC50 of 0.77 μM, indicating that the in vitro
antiviral assay used is appropriate to assess antiviral activity against SARS-CoV-2 (12).
Prezcobix/Rezolsta is a fixed-dose combination of 800 mg of the HIV
protease inhibitor darunavir (DRV) and 150 mg cobicistat, a CYP3A4 inhibitor, which is
indicated in combination with other antiretroviral agents for the treatment of HIV infection. There
are currently no definitive data on the safety and efficacy of DRV/cobicistat for treatment of
COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient
infected with SARS-CoV-2 was assessed. DRV showed no activity against SARS-CoV-2 at
clinically relevant concentrations (EC50 >100 μM). Remdesivir, used as a positive control,
showed potent antiviral activity (EC50 = 0.38 μM). Overall, the data do not support the use of
DRV for treatment of COVID-19.
Remdesivir showed strong antiviral activity against SARS-CoV-2 with an EC50 of 0.11 μM
based on visual scoring of inhibition of CPE (Figure 1a). In the same experiments, DRV did not
show any inhibition of SARS-CoV-2 induced CPE (Figure 1b; EC50 >100 μM). Similar results
were obtained using the MTT method. Remdesivir showed potent antiviral activity with an EC50
value of 0.38 μM (Figure 1a), while DRV showed no effect (EC50 >100 μM, Figure 1b). No
cytotoxicity of remdesivir or DRV was observed on Caco-2 cells with CC50 values >100 μM. The
selectivity index (CC50 / EC50) for DRV could not be calculated (>100 μM / >100 μM for SARSCoV-
2) due to the lack of antiviral activity. In contrast, remdesivir had a selectivity index of >900
by visual CPE scoring and >260 by the MTT method, confirming a strong in vitro antiviral effect
against SARS-CoV-2.
As no specific antivirals for treatment of COVID-19 are available, one avenue of clinical interest
is the use of human immunodeficiency virus (HIV) protease inhibitors (PIs) as a therapeutic
intervention. The potential for HIV PIs as a treatment for COVID-19 is mainly based on limited
virologic and clinical data on the HIV protease inhibitor lopinavir with low-dose ritonavir (as a
pharmacoenhancer; LPV/r) in patients infected with severe acute respiratory syndrome related
to a coronavirus (SARS-CoV) (4). After demonstrating the in vitro antiviral activity of LPV
against SARS-CoV-1, the clinical response of patients with SARS to a combination of LPV/r and
ribavirin was examined. Patients treated with LPV/r had lower rates of adverse clinical outcomes at day 21 following the onset of symptoms compared with historical controls (4).
However, recent data in hospitalized adults with severe confirmed COVID-19 treated with LPV/r in addition to a standard care of ventilation, oxygen, vasopressor support, antibiotics and renalreplacement therapy showed that there was no significant improvement in time to clinical
improvement or mortality at day 28 compared with the standard care (5).
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J&J HIV drug already in Covid-19 clinical trials flunks in vitro study
According to a preprint paper posted Tuesday, scientists at the company tested the drug, Prezista, against the virus in a cell culture, but found it had no activity. A combo therapy that includes Prezista's active ingredient is in clinical trials in China.
Apr 8, 2020 at 1:11 PM
Numerous drug companies have joined the fight against Covid-19, but just as some may find vaccines or therapeutics that work on the disease, it is inevitable that others will encounter failure. One example of the latter came Wednesday as scientists conducting an in vitro study at Johnson & Johnson found that an HIV drug already in clinical development for Covid-19 failed to show activity against the virus that causes it, SARS-CoV-2.
In a preprint study – meaning one that has not undergone peer review – posted to medRxiv.org, researchers at the New Brunswick, New Jersey-based drugmaker found that when they tested the drug, Prezista (darunavir), in a cell culture against Covid-19 virus that had been isolated from a patient, it displayed no antiviral activity when tested at concentrations considered clinically relevant. By contrast, when they tested another drug in clinical development, Gilead Sciences' remdesivir, on a control sample, that drug showed "potent" activity. As such, they concluded, the data do not support use of the drug to treat Covid-19.
A J&J spokesperson pointed to a public statement by the company about the lack of evidence for the drug as a Covid-19 treatment.
In addition to the branded version of Prezista marketed by J&J, Teva Pharmaceutical Industries also markets the drug as a generic. The active ingredient is also included in Prezcobix, a fixed-dose combination of Prezista and Gilead's Tybost (cobicistat).
The findings are significant because Prezcobix is already being tried on patients with Covid-19. A Phase III trial of 30 patients at the Shanghai Public Health Clinical Center in China is comparing Prezcobix on top of conventional treatments against conventional treatments alone. The study was posted on ClinicalTrials.gov in early February and, as of the last update, on March 4, was listed as still recruiting participants. The Chinese Clinical Trial Register lists another study, at Wuhan University's Zhongnan Hospital, randomizing 100 patients to receive Prezcobix, AbbVie's Kaletra (lopinavir, ritonavir) or conventional treatment. [from Jules: quilter continues to be studied as some think it might offer benefit, the study they refer to did show some benefit, perhaps it depends when in the course of the disease it is used.]
The disappointing in vitro findings for the drug follow by less than three weeks the announcement that a Chinese clinical trial of Kaletra had shown the drug did no better than standard-of-care treatments against Covid-19.
Still, numerous other drugs are in development as potential therapies for Covid-19. Remdesivir, the Gilead drug against which Prezista was tested at J&J, is in two Phase III clinical trials run by the company itself, while a Chinese study is expected to report data this month. Regeneron Pharmaceuticals and Sanofi are testing Kevzara (sarilumab), while Moderna is testing a vaccine, mRNA-1273.
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