17 December 2020

Unlocking the Opportunity in Axial Spondyloarthritis – Treating the Visible and the Invisible

AxSpA (axial spondyloarthritis) is an autoimmune disease that affects the axial skeleton, characterised by the presence of inflammatory back pain caused by sacroiliitis and genetic factor HLA-B27. Its commercial potential has been described as big as the more commonly-known rheumatoid arthritis (RA) – given its estimated prevalence is 1.7- 2.7 million patients in the US, which is significantly greater than the estimated prevalence of ~1.3M RA patients. Why then is the worldwide market size of axSpA, only $1.93 billion, considerably dwarfed by the RA market size of $27.5 billion? Where are the bottlenecks on this enormous commercial potential?

In the past, the key challenges had been misdiagnosis and the lack of a defined disease categorisation. In the US, only patients with “visible” radiographic evidence of sacroiliitis, detected through X-ray (termed as ankylosing spondylitis or radiographic axSpA (r-axSpA)), were recognised. However, 40-60% of axSpA population are “invisible” of any radiographic evidence (the so-called non-radiographic axSpA (nr-axSpA)). There is also a common misconception of nr-axSpA being a less severe form of axSpA, and treatment in the past has been aimed at addressing pain rather than halting disease progression. In fact, nr-axSpA and axSpA share the same clinical features, with both having similar disease burdens (pain, fatigue, morning stiffness, work productivity).

In the US, patients with nr-axSpA were only treated with off-label drugs until the first FDA approval of UCB’s TNF inhibitor Cimzia in March 2019, opening up the other half of the axSpA market. Despite the historic stronghold of market leader AbbVie Humira, the new nr-axSpA approval has unleashed the commercial potential of Cimzia in axSpA. In a recent Spherix survey, the majority of US rheumatologists reported to have prescribed Cimzia in at least one nr-axSpA patient between September 2019 and March 2020, driving its YoY sales growth of 22% in axSpA. Furthermore, Cimzia has also helped unlock the nr-axSpA market for another key drug class, the IL-17A. Products from Novartis (Cosentyx) and Lilly (Taltz), are further expanding market share with recent US nr-axSpA approvals in June 2020. In Europe, while nr-axSpA is already recognised and can be treated with r-axSpA therapies, recent EU label expansions in nr-axSpA is expected to further drive uptake in axSpA.

On the other hand, competition in r-axSpA is also heating up. IL-17As have been challenging Anti-TNF’s standard-of-care (SOC) positioning since the respective launches of Cosentyx and Taltz in 2016 and 2019. Novartis has also escalated its efforts in replacing Humira by investing into further data generation in spinal painhead-to-head study against Humira biosimilar, and developing an IV formulation in order to win Medicare Part B coverage (Part B covers outpatient hospital care such as IV infusion).

In 2021, the landscape will be further disrupted by the arrivals of JAK inhibitors, with the expected r-axSpA approvals of Pfizer’s Xeljanz in Q2 and AbbVie’s Rinvoq in Q3. While the JAK class has been dented by concerns on thromboembolism, it is expected to carve out a meaningful niche in r-axSpA with their unique value propositions of strong treatment benefits, fast onset of actions and the convenience of oral therapies. Additionally, spotting the opportunity, AbbVie has also expanded Rinvoq development to nr-axSpA, with a potential market entry in 2024. Gilead, another company hoping to build success with a JAK, also recently launched the largest r-axSpA clinical program amongst the JAKs for its JAK1 Jyseleca. Its development, however, has been suspended pending the resolution of its regulatory pathway after it received a FDA complete response letter related to its RA filing in August 2020.

Despite advances in disease categorisation, another key bottleneck hampers axSpA from realising its full market potential. The disease has been beset with poor diagnosis rates, commonly 5-14 years after onset due to the lack of disease awareness and a reliable biomarker. Consequently, key players such as UCB, Novartis and Lilly have significantly dialled up their promotional and educational efforts in the recent ACR conference, as well as through various disease awareness campaigns (e.g. UCB’s Gold Standard Time to Diagnosis, Novartis’ axSpA app). UCB is also setting the market for its late-stage pipeline product, the dual IL-17A/F inhibitor bimekizumab, which has so far garnered positive perception within the KOL community. Should it be approved in both r- and nr-axSpA in early 2023, UCB will be a force to be reckoned with in axSpA.

The largely untapped nr-axSpA is only starting to open up, but we can expect fierce competition across classes. Notably, expected entrants of 2 JAK inhibitors in 2021, US Humira biosimilar entry in 2022 and UCB’s IL-17A/F in 2023. More therapeutic options will also mean more aggregating efforts in raising disease awareness, which will be crucial in unmasking the facades to fully realise the commercial opportunity of axSpA.