Molnupiravar for COVID in the community: will it be a Christmas Cracker or a Complete Turkey?

It’s been a pretty depressing week or two. A new COVID variant spreading and restrictions coming back are giving a sense of Deja-Vu from last Christmas. Primary and Secondary Care are chock-a-block and a massive vaccine booster roll out has been announced. On which note, I would like to say a personal thank you, on behalf of all the NB Team, to ALL the primary care staff who have been busy keeping us safe with the vaccine programme. Whether you are volunteers, admin staff or clinicians, you are the sole reason we have even a sniff of having some freedoms and a semblance of a Christmas this year - a fact finally acknowledged in the PMs announcement over the weekend. Thank you for all you do, and will no doubt be doing more of, over the coming weeks and months.

Whilst vaccinations will remain the single most important (medical) intervention for combating COVID, the search goes on for active treatments for this spiky little ball of nastiness. And in amongst the slightly depressing trends with omicron, there is some potential Christmas cheer and optimism. We are over 18 months into this pandemic, and the only thing we (possibly) had to offer in primary care was inhaled budesonide, but that was based on relatively weak data, and the previous interim statements recommending it as an option have just been withdrawn (see CAS alert), based on a NICE review.  However, that is all changing. 

In a blitz of publicity in November, molnupiravir made its appearance. Widely reported in the press, in the medical journals, and by the Government, molnupiravir was being heralded as (yes another…) game-changer, leading to the MHRA approving it in November and the UK Government buying just shy of half a million doses for use in the community. This is the first specific anti-viral treatment that can be given to patients in the community with COVID. Molnupiravir basically works by introducing mutations and errors into the genome that ultimately stop it being able to replicate, and is given orally. 

The initial data looked very impressive. The MOVe-OUT study was terminated early due to such positive results, with interim analysis (BMJ 2021;375:n2422) suggesting a 50% reduction in the combined end-point of death or hospitalisation, with 8 deaths in the placebo group and none in the molnupiravir group. But there was concern in some quarters that the UK had jumped in with both feet without testing the ice. This was an interim analysis on relatively small numbers (775 in total) with small numbers of events, and this data was given via a press release from the drug company, with the original data still not published yet for peer review….the subject of a potential blog in its own right!

And without wanting to be the proverbial Grinch here, we do need to be aware that we are a long way off conclusively proving the efficacy of this drug, with many concerns still to be addressed (not least the need for published, peer reviewed data). Further data has now caused revision of those very impressive initial results. Based on a larger data set of ~1400 patients molnupiravir reduced the risk of hospitalisation or death by 30%, giving an absolute risk reduction of 3%, with a (still very good) NNT of ~33. This has triggered concern as to why the latter half of the data set has been so significantly different to the interim data, with a physician representing the drug company saying the drop in efficacy at the end of the trial “doesn’t really add up to us.” These are not words that engender total confidence. On the back of this further data, the FDA have been considerably more circumspect than the MHRA (BMJ 2021;375:n2984), with an advisory panel only narrowly voting 13-10 in favour of an emergency authorisation for molnupiravir. A further (theoretical) worry is that by the nature of its action altering the COVID genome, there is a risk molnupiravir may generate new spike protein variants, which if they escape may render vaccines less effective. 

Whether you see this as a glass half full or a glass half empty scenario, I’m sure we are all desperate for some positive news, and I’m really hoping the initial data on this drug translates more widely - if the 30% reduction in hospitalisations or deaths is real and the safety data stacks up, that is a substantial step in the right direction, especially as this drug can be given at home in the community, and at a much lower cost than the monoclonal antibody drugs. 

So where can my patients access this drug? Things are moving fast with announcements within the last week that Covid Medicines Delivery Units (CMDUs) will be set up across the country to deliver COVID drugs to community patients (in the very high risk groups) who are symptomatic and have had a +ve PCR. Click here for the details. It appears Ronapreve (a combination of two monoclonal antibody drugs casirivimab and imdevimab) will be the preferred option, based on better outcome data (NEJM 2021; 385:e81), but this needs to be administered via IV infusion, so for those who cannot access this, molnupiravir will be offered instead. The second option for those not in the highest risk group is to register with the PANORAMIC study. Those aged ≥50 or ≥18 in the ‘at risk’ groups (essentially the flu vaccine list) with symptoms and a +ve PCR within 5 days can self-register for the trial - click here for further information. 

Will Molnupiravir turn out to be a Christmas cracker of a drug, with positive benefits for us in the community? Or will it turn out to be a Turkey, as per North American slang….a complete flop? I’m sincerely hoping for the former, and will be topping up my glass to (at least) half full regularly! 

Best wishes to you all and I hope you can have some well-earned down time with family and friends this December.