Hidden opportunity in a time of crisis: Rheumatology’s assets at the COVID-19 frontline

Hidden opportunity in a time of crisis: Rheumatology’s assets at the COVID-19 frontline

While a COVID-19 vaccine is still a significant way ahead, drugs from I&I’s Rheumatology arsenal have emerged as possible treatments for late-stage infections. Could the potential to alleviate the world’s most pressing medical problem be a hidden opportunity for some?

In early March 2020, while the western world was still coming to terms with the impending COVID-19 pandemic, early medical reports about a potential treatment surfaced from the epicentre of the infection – China. The promising candidate was Roche’s interleukin-6 receptor (IL-6R) inhibitor, Actemra, an immunosuppressive biologic, used for the treatment of rheumatoid arthritis (RA) and systemic juvenile idiopathic arthritis (sJIA), a severe form of arthritis in children. Fast forward to late April and there are now over 23 industry- and academic-led clinical trials assessing Actemra’s potential for COVID-19 treatment around the globe. And while results can be expected as early as late May, some countries, including China, have already endorsed Actemra by including it in their COVID-19 treatment guidelines. In the meantime, Roche has significantly ramped up efforts to scale up manufacturing of this complex biologic to meet anticipated global demand.

However, Roche has not been the only company to quickly expedite research into IL-6Rs potential. Sanofi and Regeneron have also initiated global trials for their co-commercialized IL-6R, Kevzara. Intriguingly, on the back of underwhelming global sales, the two companies were planning to shift sole global rights for Kevzara back to Sanofi, as part of a cost-optimizing restructuring. However, considering recent developments, Regeneron has retained co-development for the COVID-19 indication, potentially signalling rekindled commercial interest. Unfortunately, preliminary Phase2/3 data from US has been less than impressive – Kevzara has shown negligible effects in ‘severe’ patients with investigation continuing only in the ‘critical’ cohort of COVID-19 cases. Could this data sneak-peek derail expectations for the IL-6 class? Sanofi and Regeneron remain hopeful that further Ph3 data in patients where the disease is more advanced, including data collected outside the US, will show more promise but one is certain – it won’t be long until we know the answer.

Taming the storm - promise beyond IL-6R
While IL-6R Actemra and Kevzara are leaders in terms of clinical research among advanced Rheumatology therapies, they are certainly not alone. Two oral JAK inhibitors commonly used in RA, Eli Lilly’s Olumiant and Pfizer’s Xeljanz, have also recently initiated COVID-19 clinical trials. And while the JAK’s immunosuppressive mechanism of action is likely the main rationale behind both initiatives, Lilly's Olumiant has also been suggested to have potential anti-viral properties, based on earlier computational modelling by AI firm BenevolentAI. Where JAKs have the competitive edge against IL-6Rs is in their formulation - they are taken as oral tablets rather than injections and are also chemically synthesised, allowing for easier production and scaling.

Promising COVID-19 treatments have not come only from common rheumatic diseases such as RA but also from rarer, paediatric conditions such as sJIA. Pharma giant Novartis and Swedish rare disease specialist SOBI have also entered clinical trials with their interleukin-1 inhibitors (IL-1) Ilaris and Kineret, normally used as agents against systemic inflammation. And while clinical investigation into the IL-1 class is still relatively limited, these assets could emerge as alternative and, potentially safer, option for vulnerable COVID patients who still need a well-functioning immune system to ultimately fend of the infection.

Perhaps the inclusion of IL6Rs, JAKs and IL-1s in the fight against COVID-19 is not surprising considering how all these immunosuppressants are expected to act against the infection. The emerging hypothesis behind the efficacy of IL6Rs, JAKs and IL-1s is that they may help alleviate a hyper-active immune response referred to as “cytokine storm”, which is also possible complication in children with sJIA. In COVID-19 patients, such hyper-inflammations are a leading cause of mortality.

Opportunities and challenges ahead
The uptick in clinical research is a testament that the pharmaceutical industry has embraced the potential for re-purposed Rheumatology assets to join the global arsenal against COVID-19. But beyond the opportunities in COVID-19, could these developments also bring benefits for the original rheumatic indications? Successful therapies might benefit from increased share of voice, positive brand association and HCP loyalty, potentially boosting uptake. However, to capitalize on these, pharma companies will need to carefully navigate manufacturing and supply as increased demand for their medicines could cause shortages and lead to therapy switching for rheumatology patients. Finally, there is the question of price – the hefty price tags of advanced I&I therapies seem incompatible with the wider access needed to tackle a pandemic. Set the price right and this might just be the hidden opportunity to boost a brand in decline.