Emerging Treatments Could Add to Targeted Options for Psoriasis, PsA

As the psoriasis and psoriatic arthritis (PsA) landscape continues to see more targeted treatments become approved, several emerging therapies may expand the market even further, outlined researchers of a new study.

Both psoriasis and PsA have benefitted from the addition of biologics in recent years, beginning with the emergence of tumor necrosis factor (TNF) inhibitors in 2002, followed by interleukin (IL)-12/23 inhibitors, IL-17 inhibitors, selective costimulation modulators, phosphodiesterase 4 inhibitors, and Janus kinase inhibitors.

“The identification of key cytokines involved in psoriatic disease pathogenesis has led to the development of numerous targeted systemic biologic and small molecule therapeutic options for moderate-to-severe plaque psoriasis and PsA,” commented the researchers. “Selection of one of the many approved systemic therapies for the management of plaque psoriasis and/or PsA must account for several factors. Important considerations are psoriatic disease severity, any associated psoriasis disease subtypes, type of PsA, impact of disease on quality of life, patient preference for treatment, patient treatment goals, comorbidities, and medication efficacy and safety profile.”

Emerging therapies include treatments that target IL-23 and IL-17, which could lead to the approval of new IL-23 and IL-17 inhibitors, as well as expanded the use of currently approved options.

Approved for moderate-to-severe plaque psoriasis in 2017, brodalumab has been explored in 2 phase 3 trials of patients with PsA, which revealed no new safety concerns. Similarly, the IL-23 inhibitor tildrakizumab—approved for moderate-to-severe plaque psoriasis in 2018—showed a 71%-80% ACR 20 rate among patients with PsA in a 52-week phase 2b trial. Two phase 3 trials are currently assessing the treatment in this setting.

Novel emerging treatments include bimekizumab, a selective inhibitor of IL-17A/F, which has been investigated in phase 3 trials of patients with moderate-to-severe plaque psoriasis. Data from these studies have shown that the monoclonal antibody was noninferior and superior to other approved biologics. The researchers noted that there are 2 current ongoing, multicenter phase 3 trials assessing the safety and efficacy of bimekizumab in adults and adolescents with plaque psoriasis.

Emerging data in PsA is also promising for bimekizumab, with an open-label extension study of a phase 2b trial showing ACR 20 among 62% of patients, ACR 50 among 37%, and ACR 70 among 22% of patients at week 12—indicating improvements of 20%, 50%, and 70%, respectively, across 7 different disease activity measures. ACR is commonly used as a key efficacy measure in trials of PsA.

Ongoing phase 3 trials include a randomized controls trial comparing the monoclonal antibody with adalimumab.

Safety data has shown, as with other IL-17 inhibitors, that bimekizumab was associated with mild to moderate oral candidiasis, which has not led to discontinuation of treatment.

A phase 2b trial has also been completed for sonelokimab in patients with moderate-to-severe plaque psoriasis, which showed that the treatment was significantly more effective than placebo.

“Sonelokimab is a novel trivalent camelid nanobody that binds specifically to IL-17A, IL-17F, and human serum albumin, which provides half-life extension in vivo,” explained the researchers. “Nanobodies are smaller in size compared to conventional monoclonal antibodies, thus potential for better tissue penetration.”

Data from the phase 2b trial showed no clinically significant safety signals based on depression and suicidality scales. Chron’s disease occurred in 1 patient from week 12 through week 52.

The researchers noted that phase 3 trials of sonelokimab have not yet been initiated.

Reference

Lin C, Merola J, Wallace E. Current and emerging biologic and small molecule systemic treatment options for psoriasis and psoriatic arthritis. Curr Opin Pharmacol. Published online October 10, 2022. doi:10.1016/j.coph.2022.102292