Drugmakers eye alternative to vaccines

Prevention is better than cure -- but when it comes to Covid, what happens when people can't get the vaccine, don't want it, or they're immune suppressed and it fails to stop infection? 

The hunt is on for a coronavirus treatment that can be taken as a pill soon after a confirmed positive, halting the disease in its tracks so that cases that might have been severe end up being nothing more than a bad cold.

Several companies are working on so-called oral antivirals, which would mimic what the drug Tamiflu does for influenza.

An easily storable and transportable pill would also offer practical advantages over existing treatments such as monoclonal antibodies, which are mainly injected by drips at hospital infusion centers.

One of the frontrunners in these efforts is a twice-a-day drug called Molnupiravir, which is being developed by Merck in partnership with Ridgeback Biotherapeutics.

Early results from a Phase 2 trial showed that, among dozens of volunteers who tested positive at the start, none of those who received the drug had any detectable virus by day five; while a quarter of those who received a placebo did.

The numbers are promising but too small to draw firm conclusions from, and the company is now enrolling for a Phase 3 trial involving 1,850 people with results expected by fall.

Molnupiravir belongs to a class of antiviral called "polymerase inhibitors," which work by targeting an enzyme that viruses need to copy their genetic material, and introducing mutations that leave them unable to replicate.

Because antibodies target a surface protein of the coronavirus that is continually evolving, antivirals are expected to be more variant-proof.

Currently, there's just one antiviral approved by the FDA to treat Covid, which is Remdesivir by Gilead Sciences. Remdesivir's biggest disadvantage is that it was developed as an intravenous drug and targeted at hospitalized Covid patients, among whom it was shown to modestly reduce recovery time.

But by the time Covid has progressed to severe, much of the harm to patients' health comes from their own immune systems going into overdrive and damaging their organs, rather than viral replication.  That's why the focus now is on oral formulations that can be taken within days of infection.

Roche and Atea have begun a 1,400 patient trial to study their own oral polymerase inhibitor, AT-527. Pfizer, which has developed one of pandemic's foremost vaccines, is also attracting significant attention for its oral drug PF-07321332, which has begun Phase 1 human trials in healthy patients.