WHO endorses IL-6 receptor blockers for COVID-19, Roche engaging with agency on guideline implications
Patients with severe and critical COVID-19 often suffer from an overreaction of the immune system and anti-IL-6 receptor monoclonal antibodies – tocilizumab and sarilumab – act to suppress this overreaction, said the World Health Organization (WHO); it said the treatments worked particularly well when used alongside corticosteroids.
Tocilizumab and sarilumab are only the second drugs to be recommended by the WHO for COVID-19 treatment. In guidance issued last September, it backed the use of corticosteroids: dexamethasone, hydrocortisone or prednisone for the treatment of patients with severe and critical COVID-19.
Meta-analysis
The agency said it made its recommendation supporting the use of IL-6 receptor blockers on the basis of the findings of a prospective and a living network meta-analysis that it initiated, the largest such analysis on the drugs to date.
Data from over 10 000 patients enrolled in 27 clinical trials were considered.
The meta-analyses showed that in severely or critically ill patients, administering these drugs reduce the odds of death by 13%, compared to standard care. The odds of mechanical ventilation among severe and critical patients are reduced by 28%, compared with standard care. This translates to 23 fewer patients out of a thousand needing mechanical ventilation, said the WHO.
Clinical trial investigators in 28 countries shared data with the Geneva based organization, including pre-publication data. Researchers worldwide compiled and analyzed the data.
To increase access and affordability of such drugs, WHO is urging manufacturers to reduce prices and make supplies available to low- and middle-income countries (LMICs) especially where COVID-19 is surging.
“These drugs offer hope for patients and families who are suffering from the devastating impact of severe and critical COVID-19. But IL-6 receptor blockers remain inaccessible and unaffordable for the majority of the world,” said Dr Tedros Adhanom Ghebreyesus, Director-General, WHO.
The inequitable distribution of vaccines means that people in LMICs are most susceptible to severe forms of COVID-19 and, thus, the greatest need for these drugs is in countries that currently have the least access, he said.
WHO is also encouraging companies to agree to transparent, non-exclusive voluntary licensing agreements, or to waive exclusivity rights.
In addition, the agency has launched an expression of interest for prequalification of manufacturers of IL-6 receptor blockers. Prequalification of innovator and biosimilar products aims to expand the availability of quality-assured products and to increase access through market competition and reduce prices to meet urgent public health needs, said WHO.
MSF calls on Roche to act
Médecins Sans Frontières (MSF) yesterday called on Roche, the world’s sole producer of tocilizumab, to lower the price of the drug to make it affordable and widely accessible.
“Roche must end its monopoly and urgently share the know-how, master cell lines and technology needed to produce this drug with other manufacturers across the world to ensure supply and improved access.”
Even though tocilizumab has been on the market since 2009 for treatment of rheumatologic diseases, access has remained a challenge, said MSF.
The main patent on tocilizumab expired in 2017, yet several secondary patents remain on the medicine in a number of LMICs that may cause uncertainties, according to that organization.
“Several biosimilar versions are under development, but none have been approved by a regulatory authority, meaning that despite being off-patent, Roche continue to have de facto market exclusivity that impacts the availability of the drug in the absence of sufficient supply.”
The other mAb recommended by WHO yesterday, sarilumab, is under wide patent protection globally, noted MSF.
Pharma giant 'working closely' with the WHO on implications of guidance
The WHO’s new guidance on IL-6 receptor blockers is an important development for patients hospitalized with severe or critical COVID-19, commented Roche.
Tocilizumab, branded as Actemra/RoActemra, whilst not approved for the treatment of COVID-19 in any country, has been widely used during the pandemic in the course of medical practice, and demand for this medicine has increased significantly at a global level, a spokesperson for the Swiss pharma giant told BioPharma-Reporter.
Roche, he added, has been engaging with global and national health authorities on an access and pricing strategy around the IL-6 receptor blocker specifically designed to address needs during the current pandemic.
“Our teams are working around the clock to make Actemra/RoActemra available as quickly and widely as possible, whilst managing considerable supply challenges. We have increased our own production capacity significantly and have been working with external manufacturers on transferring our technologies to further increase global supply.”
Despite all these efforts, it may still not be enough to meet the unprecedented demand for the drug, said the Roche representative.
Roche and Chugai, which are both holders of Actemra/RoActemra-related patents, have therefore decided not to assert any patents against the use of that drug in COVID-19 in LMICs during the current pandemic, which will provide legal certainty for biologic manufacturers, continued the spokesperson.
“At the same time, we strongly believe that robust intellectual property (IP) systems are a prerequisite for innovation and improving treatments for the benefit of every human being and society as a whole.
"IP protection is mandatory to address the huge healthcare challenges the world is facing – also beyond COVID-19. It has been the basis for the industry’s quick and comprehensive response to the challenges of the pandemic – an unprecedented success of healthcare innovation.”
Roche is working closely with the WHO on the implications of its guideline and on mechanisms (WHO prequalification) that may enhance access in LMICs, he said.
“In addition, we are continuing to discuss the clinical trials of Actemra/RoActemra to date with the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and other health authorities.”
Upon approval of Actemra/RoActemra for use in COVID-19, the company is planning to improve affordability of that drug across all markets, added the spokesperson.
