On January 13, UNION Therapeutics registered a Phase IIb, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study to evaluate the efficacy and safety of the phosphodiesterase-4 (PDE4) inhibitor, orismilast, in adults with moderate-to-severe plaque psoriasis (PsO). Although historically dormant compared to the injectable biologic development space, the PsO small molecule market is expected to grow significantly over the next 10 years, according to GlobalData, a leading data and analytics company. If approved, orismilast would be the second oral PDE4 inhibitor to enter the space and the third member of the class overall, trailing behind Amgen’s Otezla (apremilast) and Arcutis’ topical PDE4 inhibitor roflumilast, which is expected to gain approval later this year.

Orismilast (20mg, 30mg, and 40mg) is expected to be tested in 200 subjects, with efficacy being measured by percent change from baseline in Psoriasis Activity and Severity (PASI) scores at week 16. The proportion of patients achieving 75% reduction in symptoms (PASI75) and Investigator’s Global Assessment (IGA) score improvement are currently listed as key secondary endpoints. This trial (NCT05190419) is expected to commence both in the US and Europe.

Tiffany Chan, Immunology Analyst at GlobalData, comments: “Since the injectable biologic space is so saturated, small molecule development allows new players to enter the PsO arena. Additionally, key opinion leaders (KOLs) interviewed by GlobalData are particularly optimistic about the small molecule agents, as there is a negligible risk of drug immunogenicity compared to their biologic counterparts.

“However, while entering Phase IIB is a major developmental milestone, orismilast would actually be considered a late entrant in the PsO small-molecule space. In addition to roflumilast, orismilast joins an additional four PsO pipeline small molecule therapeutics: Dermavant’s tapinarof, Bristol Myers Squibb’s deucravacitinib, Can-Fite’s piclidenoson, and Dr. Reddy’s tepilamide fumarate.”

Orsmilast’s main competition is Otezla, which has been an industry staple for several years already. In December 2021, Otezla became the first therapy approved for all severities of PsO. Given the typical developmental timeline for this indication, it is also likely that orismilast will launch concurrently with Otezla’s patent expiry in 2028 and the subsequent launch of apremilast generics. Since generic small molecules have historically been priced at a steep discount to their branded counterparts, this could significantly curtail orismilast’s future earnings. With generic apremilast available, payers may require use of the generic as a step-therapy before initiating orismilast. If UNION wants to position orismilast as a potential first-line agent, it may be forced to price the product inexpensively in order to remain competitive. One strategy to achieve this would be partnering with a more established manufacturer so that orismilast could be contracted in a bundle with other products.

Chan adds: “Nonetheless, KOLs and payors interviewed by GlobalData believe that there are still ways for new companies to enter the space, if they are savvy with their corporate strategy. If UNION can demonstrate orismilast’s superior efficacy and safety compared to Otezla, competitively negotiate with payors, and potentially diversify into other, under-treated subtypes of psoriasis, the company may yet be able to stake a claim on the market.”