The next big disruptor in Rheumatoid Arthritis (RA) may be a TNF.
This statement may seem surprising to those with a historical perspective on the landscape, but there are good reasons why recent innovation has been channelled in this direction. Biologic drugs inhibiting tumour necrosis factor-alpha (TNFi) signalling have been around for more than 20 years and have arguably revolutionised the standard of care for RA, achieving over $255 billion in combined worldwide sales since 2004[1]. Over this period, the class has weathered multiple attempts to dethrone its place as first-line advanced therapy, including challenges from novel biologic modalities and, more recently, oral JAK inhibitors. The biologics were never able to meaningfully surpass the TNF efficacy, and the JAKs, while more efficacious, were associated with significant safety risks warranting delegation towards later lines of treatment.
While the advent of biosimilars in the US is finally bringing the sunset of commercial success for big brands like Humira, the TNFi class remains the go-to option for moderate-to-severe RA patients going on their first advanced therapy.
Considering the long existence of TNFs in the RA market, it may seem unusual that my bet for the next major winner may come from this tried and tested MoA. However, there are reasons to believe Sanofi’s oral TNFi, SAR441566, may be able to reinvigorate the TNF modality – perhaps through the only innovation avenues still available. The company hopes to leverage the historic success of SAR441566’s biologic predecessors while improving where it really matters – convenience and safety. It is not difficult to see why – broadly speaking, the I&I market has been looking for the “holy grail” of a safe and efficacious oral therapy for some time.
A prominent example is the rapid success of Amgen’s Otezla in Psoriasis, which offered a safe and orally administered option to a market dominated by injectables despite lacking in efficacy (some dermatology pundits have unofficially gone as far as coining it a “branded placebo”). In RA, the unmet need for an oral advanced therapy is also clear, considering the rapid initial uptake of JAK inhibitors, which provided convenience and stronger efficacy vs. TNFs (at the right dose), only to be halted and displaced to later lines of treatment by safety warnings coming to light through post-approval studies. If further data supports SAR441566 delivering “TNF-like” efficacy with a clean bill on safety, Sanofi may be able to position its asset early in the advanced treatment sequence where current TNFi biologics are, and ahead of a very crowded competitive environment. This will be a highly attractive option if past patient sentiment favouring the convenience of a pill is any indication.
So, are we going back to the future in RA? The next clues will be in SAR441566’s Ph2b readouts in Psoriasis and RA, expected in H1 and H2 of 2025.
Sources:
[1] Evaluate.com estimate, data obtained in Jul 2024