A simple pill, to take at home, immediately after knowing you are positive for the coronavirus still remains a dream. But the efforts to get there are not lacking. The problem is that Sars-CoV-2 is constantly evolving and, like all viruses, it uses our cells to reproduce. So finding a drug that affects a stage of viral reproduction without harming the host is not easy. And the time factor also plays a fundamental role. “The precise moment of the viral infection starts a countdown, while the virus gradually awakens the immune system, creating a narrow window of time after which an antiviral is probably useless”, explains Massimo Galli, Professor of Infectious Diseases at the University of Milan and head of the Infectious Diseases Department of the Sacco Hospital.
A “refined” experimentation
In other words, it can take anywhere from a few days to two weeks for Sars-CoV-2 to activate these immune processes. This means that any clinical trial for an antiviral requires a refined design. “Patients must have confirmed infections, but if they are already experiencing severe symptoms of Covid-19, they may be too far away to benefit from it,” says Galli. The path seems uphill, but there seems to be some hope of having more than one antiviral, even in the short term.
Loading…
Molnupiravir’s bet
Pharmaceutical giant MSD is expected to present data from an oral therapy similar to Remdesivir soon. The company is enrolling around 3,000 patients, both hospitalized and not, in a phase 2/3 study that will determine whether Molnupiravir, the drug’s name, prevents patients with mild symptoms from developing severe disease. A drug from Atea Pharmaceuticals follows: AT-527 targets a key viral replication enzyme, with a similar approach to anti-hepatitis C therapy. By the end of the year, Atea expects to have Phase 2 data for both inpatient and non-hospitalized patients, but is also planning a larger Phase 3 study in outpatients.
Pfizer antiviral
Another promise is a Pfizer antiviral, designed specifically for Sars-Cov-2, which entered the first clinical trial last month. The drug targets the core of the virus replication process, which is the 3CL enzyme, which is one of two specific to all coronaviruses. If Pfizer succeeds in reaching the goal, it could have a treatment not only for Sars-Cov-2, but also for future pandemic viruses. Pending the results on antivirals, there are other approaches that appear to provide encouraging answers in reducing mortality.
The anti-inflammatory Baricitinib
Among these, therapy with Baricitinib, an oral anti-inflammatory, which, based on the results of a study published in the New England Journal of Medicine, had already led to the authorization for emergency use by the FDA in specific patient populations. But now a new study shows its effectiveness in reducing mortality. “In Covid patients admitted to hospital Baricitinib, in addition to the standard of care with corticosteroids and Remdesivir, led to a 38% reduction in mortality”, continues Galli, specifying that this is a Phase 3 study communicated by the company ( Lilly in collaboration with Incyte and not yet published), involving 1,525 patients, “The study, which did not reach statistical significance on the primary endpoint (i.e. progression to non-invasive ventilation or mechanical ventilation or death), instead found a significant reduction in all-cause mortality by day 28 among patients treated with 4 mg daily of this drug, plus standard of care, including corticosteroids and remdesivir. A net result to which we hope to contribute soon with a large Italian study, in which about thirty centers will participate, and which should start within a week, maximum ten days ». The drug will be contrasted and compared with Remdesivir and cortisone.