The first and encouraging results arrive from the phase 2 EMPATHY trial, in which Novartis’ drug called Ensovibep is being tested. This new drug appears to be able to reduce viral loads, hospitalizations and death in a cohort of 407 people. The drug is taken intravenously in a hospital setting and the exact dosage has yet to be defined.
How does this new drug work?
We have learned that Sars-CoV2 uses a biological gateway to enter our cells: the ACE2 receptor. The means by which the virus ‘opens this door’ is the Spike protein. Most Covid19 vaccines are built on the viral Spike so that our immune system develops antibodies against it preventing the virus from entering.
Ensovibep binds to a specific portion of the Spike protein (RBD) and prevents its interaction with ACE2. Preliminary data show that Ensovibep is able to block and inhibit all variants of Sars-CoV2, including Omicron, suggesting that the block occurs in a specific and mutation-independent manner.
Advantages and disadvantages of Ensovibep
If the Ensovibep were to be approved it would be another very valuable weapon in our arsenal against Sars-CoV2, it would join with Paxlovid and Molnupiravir who have proven effective in reducing serious illness and hospitalizations. Unlike other drugs, Ensovibep acts upstream in the viral cascade and, as we have seen, prevents the virus from entering cells, preserving them from damage induced by the virus.
Furthermore, the Ensovibep has proved effective against all variants, a feature now more necessary than ever. Finally, the mechanism of action of Ensovibep is extremely specific (it blocks a region of the viral Spike). The extreme specificity of the drug should reduce the number of undesirable effects.
After having listed the advantages of Ensovibep some disadvantages should be mentioned: in fact the drug is administered intravenously. The method of administration could limit access to the drug and also its distribution. Ensovibep is a drug that does not prevent infection but avoids its deleterious effects and therefore must be taken promptly and this element could complicate its use.
Finally, in a similar way to other antivirals, in order to fully appreciate its potency it would be necessary to know exactly which patients will benefit the most, in fact the clinical benefit in a young patient without pathologies could be limited.
Take Home Messages:
1) Ensovibep is a new anti-Sars-CoV2 drug currently under investigation
2) It works by blocking the interaction between the Spike protein (key) and the human ACE2 receptor (gate)
3) The preliminary results are very encouraging and appear to reduce the risk of death and hospitalization
4) This drug could be added to the arsenal against Covid19 where for the moment vaccines remain the fundamental weapon
REF:
https://www.clinicaltrials.gov/ct2/show/NCT04828161
https://www.novartis.com/news/media-releases/novartis-and-molecular-partners-report-positive-topline-data-from-phase-2-study-ensovibep-mp0420-darpin-antiviral-therapeutic-covid-19
https://www.biorxiv.org/content/10.1101/2021.02.03.429164v3.full
Aureliano Stingi, doctor in molecular biology works in the field of precision oncology. Collaborate with the World Health Organization in the battle against Covid19-themed fake news
Twitter: @AurelianoStingi Instagram: Aureliano _Stingi
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