molnupiravir – Pediatric Infection Connection

Hang In There

Bud WiedermannDecember 26, 2021Leave a comment

No point in sugar-coating, things are likely to get worse before they get better. The news is disappointing, but we can at least hope that omicron and influenza will crest quickly and recede somewhat.

Omicron is Different

Yes, you already knew that. We certainly know it is (much) more highly transmissible but we still don't have enough data to know if severity is different. Full vaccination (primary series plus booster) is likely to be helpful against severe illness though much less so against infection itself.

Our most commonly available monoclonal antibody regimens are unlikely to be effective against omicron; at Children's National we have paused offering both the bamlanivimab/etesevimab and casinivimab/imdevimab monoclonal cocktails given the high rate of omicron in our region. Sotrovimab should be effective against omicron, but currently we don't have this agent on hand and availability is likely to be limited for the next few weeks. Note that use is limited to outpatients 12 years of age and older and weight 40 kg and greater with positive SARS-CoV-2 testing and high risk for hospitalization or death.

We now have emergency use authorization for 2 oral medications, molnupiravir and nirmatrelvir/ritonavir (Paxlovid), for treatment of mild-to-moderate COVID-19 illness. Paxlovid, consisting of 2 viral protease inhibitors, is authorized down to the 12 years of age/40 kg weight category with high risk for disease progression. Note that Paxlovid is a CYP3A inhibitor, so beware of drug interactions. Molnupiravir is less effective but can be used in adults at high risk for progression who cannot access or receive other treatment options. In the coming weeks molnupiravir is likely to be more available than Paxlovid, but note that it should not be given to children - concerns for joint problems in juvenile animals likely will delay pediatric trials. Because it is a mutagenic agent, use in pregnancy is an unknown risk and patients of reproductive age should use methods to prevent pregnancy while taking the medication and for either 4 days after (females) or 3 months after (males) the 5-day treatment course.

Another difference for omicron is that some SARS-CoV-2 tests may show false negative results. It is a little tough to keep track of new information about this, but the FDA has a great resource.

Influenza on the Rise

Influenza has been creeping up nationally and also at Children's National Hospital, though at the hospital it has not yet reached numbers that we associate with the official start of flu season. Now a preprint study suggests that the 2021-22 influenza vaccine has reduced ability to inhibit replication of the H3N2 clade most likely to be circulating this year. That could mean an antigenic mismatch for this flu season, but we won't have an estimate of that for at least a few months. Even if this is true, influenza vaccination is still very important and I would encourage everyone to be immunized - it's not too late.

A Busy Week 2

Bud WiedermannNovember 7, 20212 Comments

I am always bemoaning the fact that I don't have a reliable crystal ball, but maybe I found one in this article in the Atlantic. I took the time to read it, even though we've had a very busy week.

Vaccines for 5-11 year-olds

I'm sure you all know by now that the CDC/ACIP met on November 2 and did recommend Pfizer's COVID-19 vaccine for all 5 through 11 year-old children, noting that benefits clearly outweighed risks in this population. The presentations on November 2 largely mirrored what was presented the previous week at the FDA/VRBPAC meeting. This final seal of approval on FDA's EUA set in motion a flurry of activity for healthcare providers and parents to start the immunization process. Families can consult vaccines.gov to look for vaccination appointments nearby.

Less well known, the announcement also created a new round for the original trial participants. I spent much of November 3 and thereafter contacting parents of 5-11 year old children in our trial to let them know whether their child received vaccine or placebo. We then scheduled placebo recipients to come to our clinical trials unit to receive the first dose of the vaccine; we started this on November 4 and it is proceeding very well. Needless to say, this is an important and exciting time for these families who truly are the heroes we all thank for making it possible to provide vaccine to this age group. More to come in the coming months for the younger kids!

Another Oral Drug for COVID-19?

I always cringe when a pharmaceutical company announces significant new findings without releasing detailed data, but still I was happy to see Pfizer's apparent success for a new oral therapy, PF-07321332/ritonavir. A clinical trial of this agent for non-hospitalized high-risk adults with COVID-19 was halted early after a previously scheduled interim data analysis showed efficacy. In subjects who received drug or placebo within 5 days of symptom onset, the study drug group showed 6 of 607 recipients hospitalized with no deaths, versus 41/612 hospitalized and 10 deaths in the placebo group. We'll see what the FDA says about the data, but this could add to the treatment armamentarium eventually. Currently there are no pediatric trials for this agent in clinicaltrials.gov, nor any for the other oral agent, molnupiravir, that looked promising in recent reports. Molnupiravir is a ribonucleoside analog, while the Pfizer product consists of 2 protease inhibitors.

Thor’s Hammer to the Rescue?

Bud WiedermannOctober 3, 2021Leave a comment

This is not an immediate game-changer, but the possibility of an oral treatment for COVID-19 disease is a hopeful harbinger of a new era in the pandemic.

Molnupiravir - What is It, and What Do We Know About It?

According to the manufacturer, molnupiravir was named after Mjolnir, which, as all fans of Norse mythology or Marvel Comics know, is Thor's hammer. Unfortunately all we know about the recent study results is from the manufacturer's press release, not exactly an unbiased source. It states that the study was stopped early following a predetermined interim analysis that showed benefit of the drug compared to placebo in adults with mild to moderate COVID-19. The drug group showed 28/385 recipients hospitalized (no deaths occurred) at the 29-day follow-up period versus 53/377 in the placebo group, which included 8 deaths. Adverse events were similar in drug versus placebo recipients. I'm giving you the raw numbers to show you that these are relatively small numbers of people with short-term follow-up, so we still want to hear more about this, presumably from the FDA after data are submitted to them.

Molnupiravir is in the nucleoside analog drug class which also includes several anti-HIV and other antiviral drugs. The manufacturer states that it has efficacy against variants including delta. Although the overall efficacy might be considered modest at best, the availability of an oral treatment for COVID-19 could have a major impact in the US as well as globally. Several other manufacturers have studies of oral SARS-CoV-2 drugs in progress. This is just the start of what promises to be a real step forward. Of course, vaccinating the unimmunized will have the biggest impact on the pandemic, much more than any therapeutic intervention.

Is the End of the Surge in Sight?

If you look at almost any measure, new cases of SARS-CoV-2 infection are heading down lately, but what does this mean? The interpretation is tough because it's hard to know a unifying explanation for why things are heading down at this time. If you want to keep track of things, I'd recommend the CDC Data Tracker and, within that, the percent test positivity rates are probably most helpful. The New York Times continues their highly interactive data monitoring that can give you a quick look at local and regional numbers though not direct percent positivity rates.

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