Psoriasis is a dermatologic disease that results in itchy and scaly patches of skin, which can interfere with sleep and affect concentration. Psoriasis affects roughly 3% of the US adult population, which is over 7.5 million people affected by this disease. Symptoms of psoriasis are having patchy rashes, rashes varying in color, itching, burning, soreness, and more. There are several physical manifestations and types of psoriasis, from plaque psoriasis, nail psoriasis, guttate psoriasis, and more.
Phosphodiesterase 4 (PDE4) is an enzyme that degrades a molecule called cyclic adenosine monophosphate (cAMP) and cAMP regulates many inflammatory pathways. PDE4 inhibitors are a well-known class of medications, since it is logically a great enzyme to inhibit in order to lower inflammation.
Learn more about phosphodiesterase inhibitors here:
Orismilast is a PDE4 inhibitor being developed by UNION and being studied for treatment in moderate to severe psoriasis. A Phase 2A trial was done in Germany where 36 patients were randomized to get 30mg oral orismilast tablets or placebo for 16 weeks. Psoriasis is measured by the Psoriasis Area and Severity Index (PASI). This study showed that orismilast twice-daily group decreased in PASI score from the start of treatment to week 16 compared to placebo. Additionally, patients on orismilast had reported increased quality of life compared to the placebo group.
The most common side effects or orismilast were gastrointestinal-related issues like nausea, diarrhea, vomiting, and infections. There were more patients discontinuing their treatment when on orismilast than on placebo, however.
It is really exciting seeing a variety of PDE4 inhibitors and a variety of drugs to target inflammation early in the inflammation cascade. Another FDA approved regimen targeting psoriasis is great, but the competition in the field is heavy. As the number of drugs increase, the new target for these companies is tolerability of the drug, since gastrointestinal side effects are the most common adverse effect patients complain about class-wide. The efficacy aspect has been taken care of, the safety aspect has been taken care of, and now the fine-tuning of the medications to increase patient adherence and willingness to continue the treatment.
References:
https://www.mayoclinic.org/diseases-conditions/psoriasis/symptoms-causes/syc-20355840
Armstrong AW, Mehta MD, Schupp CW, Gondo GC, Bell SJ, Griffiths CEM. Psoriasis Prevalence in Adults in the United States. JAMA Dermatol. 2021;157(8):940-946. doi:10.1001/jamadermatol.2021.2007
Warren, RB, Strober, B, Silverberg, JI, Guttman, E, Andres, P, Felding, J, et al. Oral orismilast: Efficacy and safety in moderate-to-severe psoriasis and development of modified release tablets. J Eur Acad Dermatol Venereol. 2023; 37: 711– 720. https://doi.org/10.1111/jdv.18812
