Nonsteroidal topical agents and TYK2 inhibitors may join an already full armamentarium.
People with plaque psoriasis have a number of treatment options: topical agents, phototherapy, oral treatments and biologics. And now drugmakers are vying to create even more.
In front of the queue is Vtama (tapinarof) cream 1%, the first nonsteroidal topical agent approved to treat plaque psoriasis. Developed by Dermavant Sciences, a biotech company in Morristown, North Carolina, Vtama is a cream containing an aryl hydrocarbon receptor agonist. Aryl hydrocarbon receptors play a crucial role in the immune response and the body’s response to pollution and other exogenous factors.
Otezla (apremilast), an oral phosphodiesterase 4 (PDE4) inhibitor developed by Amgen, was approved by the FDA in December 2021 as a treatment for plaque psoriasis in adults. Adverse effects, such as severe vomiting and diarrhea or depression, may preclude certain patients from using this medication.
Roflumilast cream is a topical PDE4 inhibitor developed by Arcutis Biotherapeutics, a Southern California biotech company. PDE4 is an enzyme that promotes inflammation; inhibiting it downregulates the inflammatory cytokines responsible for symptoms of plaque psoriasis.
Following positive results from phase 3 trials DERMIS-1 and DERMIS-2, the company filed a new drug application with the FDA for the use of roflumilast cream 0.3 % once daily in the treatment of plaque psoriasis in adults and adolescents.
The FDA approved the roflumilast cream on July 29. The cream, which Arcutis is marketing under the brand name Zoryve, became available on Aug. 10, according to a company media release. Zoryve joins Vtama as a nonsteroidal topical agent for plaque psoriasis.
Meanwhile, Bristol Myers Squibb is developing deucravacitinib, an oral treatment that the company says would be the first tyrosine kinase 2 (TYK2) inhibitor. TYK2 is member of the Janus kinase (JAK) family. By homing in on TYK2, deucravacitinib inhibits signaling of interleukin (IL)-23, IL-12 and type 1 interferons, which are heavily involved in plaque psoriasis pathology. Bristol Myers Squibb says that deucravacitinib’s selectivity — it doesn’t affect JAK1, JAK2 or JAK3 — could mean that it won’t have the risk of serious side effects, such as heart attack and blood clots, that other JAK inhibitors do.
In phase 3 trials, more participants taking deucravacitinib achieved clear or almost clear skin compared with those taking placebo or Otezla. Moreover, fewer participants taking the TYK2 inhibitor discontinued treatment due to adverse events than those taking placebo or Otezla.
Deucravacitinib was approved by the FDA this past September.
Bimekizumab bumps in the road
Bimzelx (bimekizumab) is a selective IL-17A and IL-17F inhibitor developed by UCB, a Belgian pharmaceutical company. IL-17A and IL-17F are highly active cytokines in the inflammatory process of plaque psoriasis. In phase 3 trials, bimekizumab, which is administered by injection, showed promising results compared with other systemic biologics.
But UCB has run into problems gaining FDA approval for Bimzelx. COVID-19 restrictions prevented the agency from inspecting the UCB manufacturing facility, and then the FDA issued a complete response letter because of problems it identified during the inspection. But Bimzelx has been approved as a treatment of plaque psoriasis in the European Union, Great Britain, Japan, Canada and Australia.
Pfizer has two plaque psoriasis drugs that are earlier in development. PF-07038124, another topical PDE4 inhibitor, is in phase 2 studies. PF-06826647 is an oral TYK2 inhibitor, and results from a phase 2 study showed that it was significantly more effective than placebo in treating plaque psoriasis.
Rosanna Sutherby, Pharm.D., is a medical writer and community pharmacist in High Point, North Carolina.
This article was originally published by Managed Healthcare Executive.