'Treatment options for psoriasis are evolving'

"Expectations rise with the use of new oral drugs in psoriasis"

Dr. April Armstrong, Professor and Chief of Dermatology at the University of California Los Angeles (UCLA) David Geffen School of Medicine

Oral options emerged after the introduction of biologics...secured efficacy and ease of administration

Sotyktu settles as the new oral treatment option...'TYK2' mechanism receives validation

Dr.

 

April W.

 

Armstrong, Professor and Chief of Dermatology at the University of California Los Angeles (UCLA) David Geffen School of Medicine

“In the field of psoriasis, the development of many biologics has been largely abandoned due to the lack of convincing data showing similar efficacy to marketed drugs.

 

On the other hand, in the field of oral drugs, interest in the TYK2 mechanism has increased upon the introduction of Sotyktu, increasing the industry’s R&D on such oral drugs.

 

I expect to see an active oral psoriasis treatment option development in the coming years.” Dr.

 

April Armstrong, a professor at the David Geffen School of Medicine at UCLA, recently spoke to Dailypharm about her rising expectations in the future of psoriasis treatment upon the introduction of various psoriasis treatment options.

 

Professor Armstrong is an expert in the field of psoriasis, having served as chair of the Medical Board at the National Psoriasis Foundation and co-president of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

 

Psoriasis is a chronic, non-contagious skin condition with flare-ups and remissions, with an estimated prevalence of 3% in Korea and an estimated 1.5 million patients.

 

It is characterized by narrow, rice-like red patches on the skin, covered with white dead skin cells, which can grow from the size of a coin to the size of the palm of your hand when the rash becomes aggravated.

 

Psoriasis is categorized by clinical type, and in “plaque psoriasis, which accounts for 80 to 90 percent of all cases, the rash is shaped like a plaque.

 

Psoriasis is not just a skin disease, but a systemic and persistent immunologic abnormality that is difficult to cure and requires long-term management.

 

The goal of treatment for psoriasis is to improve the quality of life by improving skin lesions and controlling flare-ups and exacerbations while minimizing the side effects of medications and preventing the many systemic complications caused by chronic inflammation.

 

A variety of treatment options have already emerged for psoriasis, including TNF-α inhibitors and interleukin (IL)-inhibitors.

 

In addition, new oral therapies, such as BMS' Sotyktu, have emerged to target both therapeutic efficacy and patient convenience.

 

Sotyktu is the first TYK2 inhibitor approved for moderate-to-severe plaque psoriasis in adults.

 

Sotyktu is taken orally once daily, regardless of meals, with no dosage adjustments, expanding the patients’ options in a setting where biologics were the only treatment option available outside of the existing universal treatment.

 

Professor Armstrong emphasized that Sotyktu brought the psoriasis treatment environment a step forward and that oral formulations could be the next big R&D trend.

 

Introductino of Sotyktu...first oral treatment option to target TKY2 Sotyktu is a TYK2 inhibitor.

 

TYK2 is an important link in the signaling pathway of IL-23, a cytokine known to play a key role in the pathogenesis of psoriasis.

 

TYK2 mediates multiple cytokine pathways, such as IL-23, which in turn triggers the production of pro-inflammatory cytokines including IL-17 that promote keratinocyte proliferation and epidermal overgrowth, resulting in psoriasis.

 

As a TYK2 inhibitor, Sotyktu selectively binds to the regulatory domain of TYK2 and blocks IL-23 signaling, thereby reducing the production of IL-23 and IL-17, which in turn reduces keratinocyte proliferation.

 

“Patients with psoriasis have long suffered from a lack of adequate treatments, and only recently have started gaining access to moderately effective treatments,” said Professor Armstrong.

 

However, there is still an unmet need.

 

Healthcare providers need to ensure that patients have access to treatments that fit their preferences and lifestyle.

 

Some patients may be uncomfortable with the idea of injections.

 

Some patients avoid Injectable medications due to significant anxiety, such as fear of needles, in which case oral medications can be an alternative.” The introduction of Sotyktu expanded options for patients who have primarily been prescribed injectables.

 

In addition to the clinical trial that became the basis of its approval, Sotyktu’s efficacy and safety were confirmed in recently published 4-year patient follow-up results.

 

The study, named POETYK PSO-1,2, LTE, looked at the Psoriasis Area and Severity Index (PASI) 75 response rate and static Physician's Global Assessment (sPGA) 0/1 response rate from 52 weeks to 4 years in 513 patients who continuously received Sotyktu for 4 years.

 

Results showed that 71% of patients treated with Sotyktu maintained PASI 75 over the 4 years, and 57% of patients achieved and maintained a high standard of “clear” and “almost clear” skin.

 

“No new adverse events or signals were identified in the safety data collected over the 4 years,” said Professor Armstrong.

 

The safety profile and tolerability seen in the parent study were well maintained in the Sotyktu arm.” “In terms of safety, Sotyktu was free of serious or major adverse events, including major adverse cardiovascular events, cancer, and venous thromboembolism.

 

Also, the serious adverse events that may arise with the Janus kinase (JAK) 1/2/3 inhibitors, such as serious infections and psoriatic arthritis, were not reported with the use of Sotyktu.” Another strength of Sotyktu is that it is effective in Asian patients.

 

In the PSO-3 study, which focused on Asian patients from Korea, China, and Taiwan, the PASI response rate was approximately 10% higher than that identified in the global study.

 

“The superior data of Sotyktu identified in the Asian study may be due to the fact that Asians tend to weigh less than Westerners, as well as genetic differences,” explained Professor Armstrong.

 

“The PSO-4 clinical data in Japanese patients showed a 76% PASI 75 rate and 83% sPGA 0/1 rate at Week 16.” “However, it should be noted that both PSO-3 and 4 trials were relatively small studies compared to global studies, and PSO-4 was a single-arm study in Japanese patients.

 

Single-arm studies without control arms tend to show higher rates,” added Professor Armstrong.

 

Increased psoriasis treatment options...

 

broaden choices for patients Treatment options for psoriasis have expanded with the introduction of a variety of new drugs, including injectable and oral therapies.

 

Various treatment options, which include IL-17, IL-23, TNF-α inhibitors, and Sotyktu, are all improving the quality of life for patients with psoriasis.

 

However, Professor Armstrong suggests that the future trend in R&D for psoriasis treatments will likely shift toward oral agents.

 

“With the introduction of Sotyktu, the development of biologics (injectables) in the treatment of psoriasis has gradually faded away,” said Professor Armstrong, ”Fewer new biologics are being developed, except for those that are nearing the end of development or have already been launched in other countries and are expected to be introduced to Korea.” According to Professor Armstrong, some biologics are under clinical trials in the U.S., but many of them have been discontinued due to the lack of convincing data, showing similar efficacy to drugs already on the market.

 

In the case of IL-17 inhibitors, concerns have been raised about the exacerbation of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease, as well as oral candidiasis.

 

IL-23 inhibitors have not been associated with any significant adverse events, but there have been concerns about pain or discomfort at the injection site and upper respiratory tract infections.

 

On the other hand, the safety of oral Sotyktu is considered to be well-established with 4 years of data.

 

While other oral therapies have been associated with higher rates of adverse events such as nausea and vomiting than placebo, Sotyktu has been well tolerated, with rates of these events not significantly different from placebo, said Professor Armstrong.

 

“This is an exciting time for patients with psoriasis, due to the increasing treatment options available.

 

Contrary to how patients had to choose between safety or efficacy when opting to use oral treatment options, oral therapies have evolved since then.

 

New oral drugs such as Sotyktu have demonstrated long-term efficacy and safety comparable to first-generation biologics such as TNF-α inhibitors and IL-12/23 inhibitors,” said Professor Armstrong.

 

”The treatment options have significantly improved than in the past.”