JAK inhibitors: promising treatment for people with severe COVID-19 illness. But will they be affordable for all?

Leena Menghaney, Global IP Advisor, MSF Access Campaign

Julien Potet, MSF Access Campaign Policy Advisor, NTDs and Vaccines

More than 18 months into the pandemic, there are still very few therapeutic options for COVID-19 patients. Dexamethasone, a widely available and affordable corticosteroid now frequently used for severe and critical COVID-19 patients worldwide, was the first drug recommended for COVID-19 treatment by the World Health Organization (WHO). Tocilizumab and sarilumab (IL-6 inhibitors) were the next to be recommended for the same category of patients.

Both these medicines are expensive intravenous monoclonal antibodies (mAbs) with no approved biosimilars (except tocilizumab in India), significant intellectual property (IP) barriers, and no or very limited access in resource-limited settings.

JAK inhibitors offer promise for patients with severe COVID-19

Another class of drugs that could soon be approved to substitute or complement mAbs like tocilizumab, are the inhibitors of Janus kinases (JAK). These medicines are be taken orally and are currently approved for inflammatory and immune-mediated diseases like rheumatoid arthritis.

As opposed to the large protein-based biological medicines like tocilizumab, JAK inhibitors are small molecules. Their pathway for regulatory approval is more straightforward than that which is applied to mAbs.

For COVID-19 treatment, the most advanced along the development pipeline of JAK inhibitors so far is baricitinib. It initially received emergency use authorisation (EUA) in November 2020 from the US Food and Drug Administration (FDA) for severe and critical hospitalised COVID-19 cases, to be used with remdesivir, based on the results of a trial (ACTT-2) which showed that the combination could accelerate time to recovery and increase the chances of clinical improvement by 30%.

A recently published trial (COV-BARRIER) showed that baricitinib — even when used without remdesivir — is associated with a 40% decrease in the risk of death among severe cases, meaning that one death can be prevented for every 20 patients treated with baricitinib. These new results led to a July 2021 update in the EUA by the FDA, now allowing the drug to be used without remdesivir and thus making it simpler to treat patients.

The most recent positive clinical data comes from another oral JAK inhibitor, tofacitinib, which shows that the incidence of respiratory failure or death was also reduced by almost 40%.

The good news is that more affordable generic versions of baricitinib and tofacitinib are already available in India and Bangladesh. Generic baricitinib prices are a fraction of those charged by the patent holder, US pharmaceutical corporation Eli Lilly. One Indian manufacturer supplies baricitinib for US$0.54 (INR 30) per tablet — about 100 times less than Eli Lilly’s price of $44 (INR 3230). It is similarly priced in Bangladesh.

A treatment course of tofacitinib (total dose of 280mg over 14 days) for COVID-19 from US pharma corporation Pfizer would cost more than $1,400 in the US. In France, it would cost more than $600. Meanwhile, in India, the price per treatment course with generics is as low as $25 (INR 1800).

Overcoming high drug prices

How can the challenge of high prices for baricitinib and tofacitinib be overcome? One answer would be to import or produce generics in other countries.

But this is where things become tricky…

In many countries, the drugs are under patent and face no price competition as only the originator product is marketed. Baricitinib is widely patented, or its patent is pending, in countries hit hardest by the pandemic, including Brazil, Russia, South Africa and Indonesia. The monopoly is due to expire only in 2029 and could even be extended further in countries with patent-term extension. The drug is also patented in India; Eli Lilly granted a voluntary license (VL) to generic companies to produce the drug locally, but under this VL the generics cannot be exported to other countries where it is also urgently needed.

While the basic patent on tofacitinib expired in 2020 in many countries, including the US, additional secondary patents extending to 2025 and beyond have already been filed by Pfizer. Generic companies that have sought approval from the FDA to sell a generic version of the medicine have faced litigation from Pfizer. This has created a chilling effect for the market entry of affordable generics.

Are these additional patents Pfizer applied for merited? No. They are classic examples of patent ‘evergreening’ by the pharma industry. The company is filing patents simply to extend its market monopoly on the medicine. This is an all-too-familiar move by companies which aim to maximise profits; they seek to artificially extend the term of monopoly on known medicines, whereas the additional patents are not linked to any genuine innovation.

The case of tofacitinib is the epitome of this pharma-industry strategy to maximise profits. Luckily India’s legal patentability criteria do not encourage the grant of unmerited evergreening patent claims. Thus, several generic manufacturers have entered the supply chain after successfully challenging evergreening patent claims and gaining approval in the last couple of years from the Indian drug regulatory authority. In practice, Pfizer could still hold a monopoly in many other countries where those evergreening patents stand. As a result, Pfizer can continue to charge an exorbitant price.

Why we need the TRIPS waiver

Medicines like baricitinib and tofacitinib make a good case for the TRIPS waiver currently under negotiation at the World Trade Organization (WTO). A waiver of IP barriers allowed under the WTO’s rules would remove the effect of Pfizer’s and Eli Lilly’s patents around the world, and countries that choose to implement the waiver could facilitate the increased production of generics, thus drastically improving the availability and affordability of these medicines.

But the TRIPS waiver is far from becoming a reality; after nearly one year of delay, the United Kingdom, Switzerland, Norway, and the European Union are still blocking negotiations to get the waiver adopted, despite the waiver’s support by over 100 countries. Meanwhile people in Africa, Asia, and Latin America are dying for lack of access to affordable COVID-19 treatments, as well as vaccines and tests. Until progress on the waiver is made, only ad hoc political pressure can help.

That’s why we say now: Please, EU, UK, Switzerland and Norway, stop blocking the waiver negotiation and let other countries have this critical legal tool to boost production and access of all COVID-19 medical tools. And to all governments, stop granting evergreening patents, and use the domestic legal options you already have to overcome patent barriers. And to the pharma corporations Pfizer and Eli Lilly, we call on you to not enforce your patents on these drugs globally. Leave the door open for affordable generics. Stop your harmful evergreening and monopoly practices! Put people over profits.

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This blog is a place to reflect on our experiences working for access to medicines. For the official MSF Access Campaign website please visit msfaccess.org.