On 22 April 2022, the World Health Organisation (WHO) said Pfizer’s oral antiviral drug Paxlovid was “strongly recommended” for patients with non-severe Covid-19 who are at highest risk of developing severe disease and hospitalisation, such as unvaccinated, older, or immunosuppressed patients.

The recommendation was based on new data from two randomised controlled trials involving 3,078 patients. The data show that the risk of hospitalisation was reduced by 85% following this treatment, the WHO said in a statement. In a high-risk group (over 10% risk of hospitalisation), that meant 84 fewer hospitalisations per 1,000 patients.

The drug

Paxlovid consists of nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use. It was given emergency use authorisation (EUA) by the USFDA in December last year.

Nirmatrelvir inhibits a viral enzyme called protease that is necessary for the virus to replicate itself inside the host cell. Ritonavir slows down the breakdown of nirmatrelvir in order to help it remain in the body for longer at higher concentrations.

A drug like nirmatrelvir is considered to have an advantage over vaccines because it attacks vulnerability in the virus that does not mutate like spike proteins — which vaccines target — do. As a result, the medication is seen to be effective against all variants. (The Omicron wave showed that in a very large number of cases, vaccines are unable to prevent infection, even though they do prevent serious illness and deaths.)

Even before the WHO’s latest endorsement, Paxlovid was seen as a wonder drug that presented a dramatic new advantage in the battle against the coronavirus. A second oral Covid-19 drug, molnupiravir, manufactured by Merck and Ridgeback, too received FDA authorisation in December last year, but showed a somewhat lower efficacy in clinical trials.

Paxlovid is administered as three tablets — two of nirmatrelvir and one of ritonavir — taken together orally twice daily for five days, that is, a total of 30 tablets. The USFDA authorised Paxlovid for use only up to five consecutive days.

The EUA for Paxlovid was based on clinical data that showed a reduced risk of hospitalisation or death by 89 per cent within three days of the onset of symptoms, and 88 per cent within five days of the onset of symptoms, compared to the placebo group.

The European Medicines Agency (EMA) issued advice that Paxlovid can be used to treat adults with Covid-19 who do not require supplemental oxygen and who are at increased risk of progressing to severe disease.

Generic versions

On 16 November last year, Pfizer had announced it had signed a voluntary licence agreement for Paxlovid that would facilitate the production and distribution of the drug by granting sub-licences to qualified generic medicine manufacturers.

Pfizer’s licensing agreement with the United Nations-backed public health organisation Medicines Patent Pool (MPP) was intended to enable the supply of the medicines to 95 low- and middle-income countries including India, comprising approximately 53% of the world’s population.

It was announced at the time that Pfizer would not receive royalties on sales in low-income countries, and that royalties would be waived on sales in all countries covered by the agreement for as long as Covid-19 remained classified as a Public Health Emergency of International Concern by WHO.

Subsequently, on 17 March this year, the MPP announced that it had signed agreements with 35 companies to manufacture the generic version of nirmatrelvir, which in combination with a low dose of ritonavir can be supplied in 95 low- and middle-income countries. Six companies will produce the drug substance, nine will produce the drug product, and the rest will do both, the MPP said in a release.

The companies are located, besides India, in Bangladesh, Brazil, China, Dominican Republic, Jordan, Israel, Mexico, Pakistan, Serbia, Republic of Korea, and Vietnam.

The MPP, founded by the Geneva-based Unitaid, works to increase access to, and facilitate the development of, life-saving medicines for low- and middle-income countries. MPP partners with civil society, governments, international organisations, industry, patient groups, and other stakeholders to prioritise and license needed medicines and pool intellectual property to encourage generic manufacture and the development of new formulations.

Drug in India

Nineteen of the 35 companies with which the MPP has signed sub-licensing agreements are Indian, and they include drugmakers such as Bengaluru-based Biocon Ltd; Mumbai-based Glenmark Pharmaceuticals, Sun Pharmaceuticals, and Cipla; Ahmedabad headquartered Torrent Pharmaceuticals and Cadila Pharmaceuticals; Hetero Drugs and Laurus Labs of Hyderabad; and Emcure Pharmaceuticals of Pune.

It was reported earlier this week that Hetero’s drug could be available at chemists’ very soon, but no confirmation was available.

In its 22 April 2022 statement, WHO said it was “extremely concerned” that low- and middle-income countries could be pushed to the “end of the queue” while accessing Paxlovid treatment — in the same way these countries had suffered when it came to the supply of Covid-19 vaccines. It said that Pfizer’s licensing agreement with the MPP limited the number of countries that can benefit from generic production of the medicine.

Push in the US

The Biden administration is aiming to expand access to oral antiviral treatments like Paxlovid by doubling the number of locations at which they are available, the White House said on 26 April 2022.

Currently, pharmacies were dependent on states to obtain the pills. The government sends the treatments to select pharmacies, as well as directly to states and community centres. Under the current system, the treatments are available in around 20,000 locations.

The administration now expects to increase their direct distribution to over 30,000 locations and reach 40,000 sites over the coming weeks, quoting an official.

Demand for Paxlovid has been unexpectedly light due to complicated eligibility requirements, reduced testing, and potential for drug interactions. The US has agreed to buy up to 20 million pills at around $530 a course, and Pfizer is on pace to produce 3.5 million courses earmarked for US use by the end of April.