Psoriasis, the chronic inflammatory skin disease, remains short of treatment options
In the most common form, plaques can appear anywhere on the body but are particularly common on the scalp, trunk, elbows/knees and elsewhere on the limbs.
Patients commonly develop inflammatory arthritis, cardiometabolic diseases and even mental health problems. It cannot be cured. It can, however, be managed with treatments including topical products and monoclonal antibodies.
Some drugs, such as methotrexate, can be given orally, but there are few effective options for systemic treatments that do not require injections. Another potential oral treatment is being developed by Danish company, Union Therapeutics, in collaboration with Innovent Biologics.
Orismilast is a second-generation phosphodiesterase-4 inhibitor, with selectivity for the PDE4B and PDE4D subtypes, and is able to modulate a broad range of the proinflammatory cytokines involved in psoriasis. A prospective, randomised, double-blind, placebo-controlled Phase IIa trial has been done.1
Patients with moderate to severe psoriasis were given 30 mg immediate release (IR) oral doses of orismilast or a placebo for 16 weeks. Treatment gave a significant improvement in the mean Psoriasis Area Severity Index (PASI) score at week 16 compared with the placebo.
This was followed by a Phase I trial in three parts.2 In the first, healthy participants were given an open label single 30 mg dose of orismilast modified release (MR) and IR; in the second, again open label, they were given one or the other — either fasted or after a low-fat or high-fat meal; in the third, they were given up to 60 mg of MR orismilast twice a day or a placebo for 17 days in a double-blind manner.
The IR and MR versions had comparable pharmacokinetic properties, whereas the MR version caused fewer gastrointestinal adverse events. The MR formulation was selected for further development.
Top line results of a randomised, double-blind, placebo-controlled, parallel group, dose ranging Phase IIb study in 202 patients have been released via press release. Subjects were randomised to receive one of three oral doses of orismilast or a placebo twice a day.
All the patients given the active achieved the primary endpoint of a reduction in PASI from baseline to week 16 compared with the placebo. Statistical significance was reached after 4 weeks. The drug is also being investigated as a potential treatment for two other inflammatory skin conditions: hidradenitis suppurativa and atopic dermatitis.