The lupus treatment landscape could soon welcome an entrant if a first-in-class anti-interferon monoclonal antibody (mAb) continues to hit clinical-trial targets. AstraZeneca and its biologics R&D branch, MedImmune, are developing anifrolumab, an investigational monoclonal antibody that blocks type 1 interferons to treat moderate to severe systemic lupus erythematosus (SLE).
The commercial potential in lupus is great, but developers are cautious owing to former late-stage failures, among them Eli Lilly’s tabalumab. Research and consulting firm GlobalData expects the lupus market to almost triple, from $1.2 billion in 2015 to $3.2 billion by 2025 across seven major markets.
“Physicians are eager for new treatments for SLE but will not overlook the balance between efficacy, safety, and cost,” says Anita Agier, head of Disease Atlas, GfK Health.
SLE is a systemic inflammatory autoimmune disease that can affect any organ or tissue. One of its severest manifestations includes renal involvement, known as lupus nephritis (LN). Though the etiology of SLE and LN is not fully understood, genetic and environmental factors are known disease contributors.
“The heterogeneous patient population makes lupus difficult from a trial point of view,” says Stephan Gauldie, SVP of strategy consulting at Back Bay Life Science Advisors. “Developers must target patient subsets.”
According to Agier, AstraZeneca can build upon its strong Phase II results demonstrating that anifrolumab significantly reduced disease activity. But while investments in investigational lupus agents appear to be heating up, late-stage clinical failure continues to be a major hurdle to market entry.
“A lot of the failures have boiled down to choosing the right patient population and identifying the correct end point for study,” Gauldie notes.
Even if anifrolumab successfully navigates the clinical-trial process, there’s another challenge waiting on the market: Human Genome Sciences’ Benlysta (belimumab). According to Agier, in order to have a substantial impact upon launch and advance the current standard of care, anifrolumab will need to show significant improvement to placebo and clear efficacy differentiation from Benlysta.
Another competitive challenge could come from Bristol-Myers Squibb, currently studying Orencia (abatacept), an anti-PD1 antibody approved to treat rheumatoid arthritis, in SLE.
“With positive trial results, anifrolumab is expected to take some share of moderate to severe lupus patients from Benlysta and create an opening for new patients to benefit from novel therapies,” she says.
Currently enrolling for Phase III studies, anifrolumab is being developed with a type I IFN gene signature test to identify patients likely to benefit from treatment.