Plaque psoriasis, the most common form of the skin disease psoriasis, causes dry and scaly skin patches. Psoriatic arthritis (PsA), a form of inflammatory arthritis, is characterised by joint pain, stiffness, and swelling.
While there are available treatments, patients and clinicians still seek options with better tolerability profiles and longer-lasting efficacy. The drug development landscape is crowded with treatment candidates, but each poses distinct challenges.
At least three experimental treatments at the Phase II or Phase III stage in plaque psoriasis have trial results expected in the second half of 2022: Lipidor’s AKP-02, Hengyi’s HPP-737, and Amgen’s ABP-654. Galapagos’ Jyseleca (filgotinib) has expected results this year for a Phase II PsA trial. Meanwhile, at least four Phase III trials in psoriasis and one Phase III study in PsA have expected completions in the next six months.
Under current standards of care, patients with mild-to-moderate plaque psoriasis rely on topical approaches. Most patients with moderate-to-severe disease receive biologics to modulate the immune system and reduce inflammation. These include tumour necrosis factor (TNF) alpha blockers like AbbVie’s Humira (adalimumab) and antibodies targeting interleukin like as AbbVie’s Skyrizi (risankizumab-rzaa). Meanwhile, most patients with PsA take anti-inflammatory drugs followed by corticosteroids and anti-rheumatic drugs, depending on disease severity.
In plaque psoriasis, drug development for small molecules is gaining steam despite the prevalence of approved biologics. “The pipeline for biologics has cooled down a little bit,” says Dr George Han, associate professor of dermatology and director of clinical trials and teledermatology at Zucker School of Medicine. “We’re dealing with kind of a new frontier and new era.”
Can Lipidor’s psoriasis spray stick?
Lipidor is testing AKP-02, a sprayable combination of a glucocorticoid steroid and a form of vitamin D, in mild-to-moderate plaque psoriasis. AKP-02 has topline Phase III trial results expected for the completed study in the third quarter of 2022.
The 294-patient, placebo-controlled study (NCT05249972) compares AKP-02 to Leo Pharma’s topical foam Enstilar. AKP-02 and Enstilar both combine the glucocorticoid steroid betamethasone dipropionate and the vitamin D analogue calcipotriol. The US Food and Drug Administration (FDA) approved Enstilar in 2015.
However, Han notes that combo agents still have the downside tolerability concerns of traditional topical steroid use. “I don't think that people love the idea of these combo agents,” he says, although adding it is still helpful to add more treatments to the arsenal.
Forthcoming trial results will reveal AKP-02’s effect along the primary endpoint of change in the Psoriasis Area and Severity Index (PASI). PASI is a 72-point scale for measuring skin lesions and among the most common skin psoriasis endpoints. Secondary endpoints include measures of disease severity specific to the scalp.
vTv tackles PDE4 pathway
vTv Therapeutics’s small molecule HPP-737 has Phase II data expected in the second half of 2022 for moderate-to-severe plaque psoriasis. As a primary endpoint, the 250-patient trial (CTR20210010) is testing of patients with a PASI score at least 75% below baseline (PASI 75).
The study is based in China, and Hengyi Biomedical Technology is the sponsor. vTv partnered with Newsoara Biopharma in 2018 to develop and commercialise HPP-737 in China. vTv has not specified whether it plans to further develop the drug outside of China.
HPP-737 targets the same phosphodiesterase type 4 (PDE4) pathway as Amgen’s oral pill Otezla (apremilast) and Arcutis’s tropical cream Zoryve (roflumilast), both of which have FDA approval. As a result, it could be tough for a new PDE4 inhibitor like HPP-737 to differentiate itself. “I don't think that there’s going to be a night and day difference in terms of efficacy,” Han says of new treatment candidates targeting PDE4.
Amgen eyes second biosimilar test
Amgen has two Phase III trials testing APB-64 as a biosimilar to Janssen’s Stelera (ustekinumab) for moderate-to-severe plaque psoriasis. One 563-patient study (NCT04607980) reported positive topline results in April, and the second 494-patient trial has results expected in 2022 (NCT04761627).
The first Phase III trial reported Amgen met its primary endpoint PASI improvement, showing no clinically meaningful difference to Stelera. The second ongoing 52-week trial is determining whether patients can switch between APB-64 and Stelera, using co-primary endpoints of area under the curve over the dosing interval (AUCtau) and maximum concentration (CMax).
Stelara is a human interleukin-12 and -23 antagonist with 2009 FDA approval for treating plaque psoriasis, with additional approvals in PsA, Chron’s disease, and ulcerative colitis (UC). In plaque psoriasis, Boehringer Ingelheim’s Cyltezo (adalimumab-adbm) and Sandoz’s Erelzi (etanercept-szzs) are biosimilars to Humira and Enbrel, respectively.
Galapagos study JAK inhibitor side effects
Meanwhile, Galapagos’ Jyseleca, which has FDA approval for rheumatoid arthritis and UC, is in a Phase II trial recruiting PsA patients. The 109-patient MANTA-RAy trial (NCT03926195) tests Jyseleca’s effect on semen parameters in males with active PsA, rheumatoid arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis. Phase II results expected in the second half of 2022.
Jyseleca is a Janus kinase (JAK) inhibitor, a mechanism that has been the subject of FDA-mandated black box warnings. “[There’s] no doubt that the JAK approach can work,” Han says, however adding that its safety profile is a legitimate concern. JAK inhibitors can suppress the immune system, increasing the risk of illness and certain cancers.
Trial completions and the road ahead
Beyond the four trials with expected results, at least five additional Phase III trials have completions expected in the second half of 2022. These include OrthoDermatologics’ Duobrii, Reliance’s RTPR-046, Sun Pharma’s tildrakizumab, Tianjin Hemay’s Hemay005, and UCB’s bimekizumab.
Looking ahead, next steps in the skin and musculoskeletal psoriasis field could be pursuing personalised endpoints and treatments, Han says. This could include more uses of PASI scores tailored to specific parts of the body, as well as treatments personalised according to certain genetic factors and environment triggers, he notes.
In the meantime, a busy slate of late-stage trial results and completions could shed light on the future of drug development in plaque psoriasis and PsA.