Highlights from

WCD 2019

World Congress of Dermatology

Milan 10-15 June 2019

Novel treatment options for many dermatologic indications

More and more new oral small molecules are entering the dermatologic arena. A relevant advantage over biologics is their oral bioavailability.

Small molecule inhibitors are organic compounds with different chemical structures and molecular weights ranging from 500 to 900 Da. As Prof. Lone Skov (Herlev-Gentofte Hospital, Denmark) pointed out, they have a simple structure and are easy to produce; hence, they are much cheaper than biologics [1,2]. Small molecules can easily diffuse across cell membranes to reach intracellular sites. Once the inhibitor enters the cells, it affects various other molecules and reduces cellular levels of specific proteins [3]. In comparison to larger molecules such as monoclonal antibodies, they have the advantage of possible oral administration and ease of combination with other treatments [3].

TYK2 inhibitor promising in psoriasis

Prof. Lars Iversen (Aarhus University Hospital, Denmark) pointed out that some small molecules have already been used for decades in the treatment of psoriasis [4]. In Germany and the Netherlands, methylfumarate has been the mainstay of treatment for psoriasis. Apremilast is a novel treatment option, approved for the therapy of psoriasis and psoriatic arthritis.

The JAK/STAT signalling pathway is also important in psoriasis. There are 4 Janus kinase (JAK) family members, JAK1, JAK2, JAK3, and TYK2. “A phase 2 study showed that TYK2 inhibition is very promising,” said Prof. Iversen. In this double-blind, phase 2, dose-finding trial, the TYK2 inhibitor BMS-986165 was assessed in patients with moderate-to-severe psoriasis. In the highest dose (12 mg daily), 75% of patients reached a Psoriasis Area and Severity Index (PASI) 75 response after 12 weeks (P<0.01 compared with placebo) [5]. Larger and longer-duration trials of this drug are required to determine its safety and durability of effect in patients with psoriasis. “I believe that small molecules will definitely have a future in therapy of psoriasis,” concluded Prof. Iversen.

  1. Skov L. 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.
  2. Veber DF, et al. J Med Chem 2002;45:2615-23.
  3. Arkin MR, Wells JA. Nat Rev Drug Discov 2004:3:301-17.
  4. Iversen L. 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.
  5. Papp K, et al. N Engl J Med 2018; 379:1313-1321.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.