The World Health Organization (WHO) has recommended Paxlovid, the antiviral medicine produced by Pfizer, for patients with COVID-19 at high risk of developing severe disease – but it is concerned about limited access to the life-saving medicine.

Friday’s WHO recommendation is aimed at “patients with non-severe COVID-19 who are at highest risk of developing severe disease and hospitalization, such as unvaccinated, older, or immunosuppressed patients”. 

It comes after a recent clinical trial of over 3000 patients found that Paxlovid reduced the need for COVID-related hospitalisation by 85% in high-risk patients who were given the medication early on in their infection.

Lack of availability

But the WHO added that “availability, lack of price transparency in bilateral deals made by the producer, and the need for prompt and accurate testing before administering it, are turning this life-saving medicine into a major challenge for low- and middle-income countries”.

Lisa Hedman, WHO technical officer for access to medicines, noted that the Paxlovid deals reported in the public domain “show a total that appears to be within Pfizer’s production capacity, which they’ve estimated to be approximately 80 to 100 billion treatments per year”. 

However, Hedman told a media briefing on Thurday, “not all deals are reported in the public domain”, and the WHO was aware of “several large procurers, including to multilateral deals and a couple of countries” that “could actually strain supply in the short term”.

Pharma flags regulatory and health system barriers

Pharmaceutical manufacturers including Pfizer also flagged the problem of access to Paxlovid at a media briefing last week – but cited the main barriers as lack of swift regulatory approval, allocation strategies, health systems capacity, and a lack of COVID-19 testing (the antiviral is only effective if it’s given to people early on in their infection), 

Last month Pfizer announced it would supply UNICEF with up to four million treatment courses for 95 low- and middle-income countries, pending authorization or approval.

“Supplying to UNICEF is an important part of our comprehensive strategy to accelerate access to Paxlovid to treat COVID-19 infection as quickly as possible and at an affordable price in order to decrease the strain on healthcare systems and help save lives in low- and middle-income countries,” said Pfizer CEO Albert Bourla.

Last November, Pfizer signed a voluntary licensing agreement with the Medicines Patent Pool (MPP) enabling it to granting sub-licenses to qualified generic medicine manufacturers to produce and supply 95 countries with Paxlovid.

This covers “approximately 53% of the world’s population”, including “all low- and lower-middle-income countries and some upper-middle-income countries in sub-Saharan Africa as well as countries that have transitioned from lower-middle to upper-middle-income status in the past five years”, according to a media release.

Last week, Bourla told a media briefing hosted by International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) that almost 250 companies had indicated their interest in producing Paxlovid to the MCC, which in turn had suggested around 35 companies.

“I don’t think that they will be able to manufacture pretty soon though, although it is very, very easy to do it, and they will do it in already existing facilities,” said Bourla.

“But right now, my concern is what do we do in the meantime for these countries. And this is why we signed an agreement with UNICEF to provide them at-cost, millions of doses that can go to countries, [and] after that the generic companies can take over and provide those doses.”

Call for transparency

The WHO noted on Friday that, since the MCC agreement had been signed, “several generic companies are in discussion with WHO Prequalification but that it may take some time to comply with international standards before they can supply the medicine internationally”.

“WHO therefore strongly recommends that Pfizer make its pricing and deals more transparent and that it enlarge the geographical scope of its licence with the Medicines Patent Pool so that more generic manufacturers may start to produce the medicine and make it available faster at affordable prices,” the organisation added.

“Ninety-five countries is a good number, but WHO would really like to see that number expanded to include more countries to recognise the need for equitable access across really the broadest group of countries possible,” said WHO’s Hedman.

Lack of testing

A significant access barrier to Paxlovid is the global drop in COVID-19 testing amid the perception that the pandemic is over. In addition, only 21.5% of tests administered worldwide have been used in low- and lower-middle-income countries, despite these countries comprising 50.8% of the global population, according to the global test tracker, FIND.

These countries also tend to have lower vaccination rates, which means their populations are more vulnerable to severe disease. Yet only people caught with early infection can benefit from Paxlovid.

On Thursday, the Africa Centre for Disease Control reported a 23% drop in tests over the past week despite five African countries experiencing a fifth COVID-19 wave.

Danger of drug-on-drug interactions

WHO official Dr Janet Diaz, explained at a media briefing on Thursday that “Paxlovid is made up of two medicines, nirmatrelvir and ritonavir. The nirmatrelvir inhibits the SARS-CoV2 protease and thus stops viral replication”

Diaz, who is the WHO’s COVID Clinical Care lead, added that nirmatrelvir is “co-administered with ritonavir,  an HIV protease inhibitor that boosts the effect of the nirmatrelvir but it itself does not exert any antiviral effect against SARS-CoV2 so this is considered a monotherapy antiviral.”

However, Diaz warned that Paxlovid was not to be given to pregnant or breastfeeding women or children, as it had not been tested on these groups.

“This drug does also have many possible drug-to-drug interactions. And this is because of the effect of ritonavir on an enzyme that’s important in the metabolism of other drugs,” warned Diaz. 

“So it is important if you are a patient that you tell your doctor what other medications you may be taking so they can do a quick check to see if there are any serious possibilities of a serious drug-to-drug interaction.”

Image Credits: Pfizer .