ESK-001 for Psoriasis

(ONWARD1 Trial)

Recruiting at 40 trial locations

Overseen By Alumis Information

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: Alumis Inc

Must not be taking: Biologics, Immunosuppressants, JAK inhibitors, others

Disqualifiers: Nonplaque psoriasis, Immune-mediated conditions, Pregnancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

840 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a new treatment, ESK-001, can reduce symptoms of moderate to severe plaque psoriasis, a condition causing red, scaly skin patches. The trial also evaluates the safety of ESK-001 compared to a placebo (a pill with no active drug) and an existing psoriasis medication, apremilast. Ideal participants have had plaque psoriasis for at least six months, with noticeable patches covering a significant body area. Participants will take a daily pill, visit the clinic for tests, and answer questions about their condition and quality of life for 24 weeks. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications before joining the trial. Specifically, you must not have used topical treatments for psoriasis within 2 weeks, phototherapy or systemic treatments within 4 weeks, and certain biologic agents or immunosuppressants within specified time frames before the study starts.

Is there any evidence suggesting that ESK-001 is likely to be safe for humans?

Research has shown that ESK-001 was well-tolerated in earlier studies. In long-term observations, patients taking ESK-001 experienced some side effects, but they were usually mild. Serious side effects were uncommon, with only six serious cases reported as of May 31, 2024. Researchers continue to develop this treatment to ensure its safety for people with plaque psoriasis. While more research is needed, these findings support the ongoing study of ESK-001’s safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for psoriasis?

Unlike typical treatments for psoriasis, which often include biologics and topical therapies, ESK-001 is unique because it is administered as an oral tablet, offering a potentially more convenient option. Researchers are excited about ESK-001 because it introduces a novel mechanism of action that differs from standard treatments, which generally focus on immune modulation. This new approach could lead to improved efficacy and tolerability for patients with psoriasis, making it a promising candidate in the quest for better management of the condition.

What evidence suggests that ESK-001 might be an effective treatment for psoriasis?

Research has shown that ESK-001, one of the treatments in this trial, targets a protein linked to inflammation and has yielded promising results for psoriasis. In earlier studies, many participants experienced significant improvements in their psoriasis symptoms. Specifically, 77.5% of patients achieved at least a 75% reduction in symptoms, as measured by the Psoriasis Area and Severity Index (PASI). The benefits of the drug persisted or even improved over time, indicating its long-term effectiveness. Patients also reported an enhanced quality of life after using ESK-001. Overall, these findings suggest ESK-001 could effectively reduce psoriasis severity. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults aged 18+ with moderate to severe plaque psoriasis for at least 6 months can join this study. They'll take a daily drug for half a year, visit the clinic regularly, and report on their skin condition, itchiness, and life quality changes.

Inclusion Criteria

Have you been diagnosed with Plaque Psoriasis?

Exclusion Criteria

Have you been diagnosed with Inflammatory Bowel Disease?

Have you been hospitalized for cardiovascular disease in the last 3 months?

Do you have recurring herpes infection or an active infection for Hepatitis B, Hepatitis C, or HIV?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ESK-001, placebo, or apremilast daily for 24 weeks. They will visit the clinic for checkups, tests, and assessments.

24 weeks

Regular clinic visits for checkups and tests

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of health issues and side effects.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ESK-001

Trial Overview The trial is testing ESK-001's effectiveness in treating plaque psoriasis compared to a placebo (dummy pill) and Apremilast (an approved treatment). Participants will be monitored through clinic visits, questionnaires, health checks, heart activity tests, and by providing blood/urine samples.

How Is the Trial Designed?

Group I: ESK-001 Experimental Treatment 1 Intervention

ESK-001 administered as an oral tablet

Group II: Apremilast Active Control 1 Intervention

Apremilast administered as an oral capsule

Group III: Placebo Placebo Group 1 Intervention

Matching oral placebo

Who Is Running the Clinical Trial?

Alumis Inc

Lead Sponsor

Trials

9

Recruited

4,200+

Published Research Related to This Trial

In two phase III studies involving 1861 patients with moderate to severe plaque psoriasis, tofacitinib significantly improved health-related quality of life, with a higher percentage of patients achieving a Dermatology Life Quality Index score of 1 or less compared to placebo at week 16, and these improvements were maintained through week 52.

Tofacitinib also led to rapid relief from itch, with improvements noticeable just one day after starting treatment, and a greater proportion of patients reported satisfaction with the treatment compared to those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib improves pruritus and health-related quality of life up to 52 weeks: Results from 2 randomized phase III trials in patients with moderate to severe plaque psoriasis. Feldman, SR., Thaçi, D., Gooderham, M., et al.[2017]

The PTK inhibitor AG-1571 (SU-5271) effectively inhibits the proliferation of psoriatic keratinocytes, showing a strong correlation with its ability to inhibit the epidermal growth factor receptor (EGFR), which is implicated in psoriasis.

Recent in vivo models of psoriasis provide promising platforms for evaluating PTK inhibitors, potentially leading to new targeted therapies for managing this skin condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological activity of tyrosine kinase inhibitors: novel agents for psoriasis therapy. Ben-Bassat, H.[2009]

Biological therapies for psoriasis, including monoclonal antibodies and recombinant proteins, target specific pathways in the disease, making them potentially safer and more effective than traditional treatments.

Four biological agents—alefacept, efalizumab, etanercept, and infliximab—are already in clinical use, with many more under investigation, highlighting a significant advancement in psoriasis treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologicals dramatic advances in the treatment of psoriasis. Wilsmann-Theis, D., Martin, S., Reber, M., et al.[2019]

Targeted biologic therapies that focus on interleukin (IL)-17 and IL-23 have proven to be highly effective in treating psoriasis, highlighting the significance of the IL-23/Th17 cell pathway in the disease's development.

While many patients with mild psoriasis could benefit from topical treatments, there is a strong preference for safe and effective oral medications; however, current JAK inhibitors may not fully meet this need due to concerns about their safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging systemic drugs in the treatment of plaque psoriasis. Balogh, EA., Bashyam, AM., Ghamrawi, RI., et al.[2021]

Inhibition of Lymphocyte-specific protein tyrosine kinase (Lck) using the inhibitor A-770041 significantly reduced clinical features of psoriasis in mice, such as skin thickness and inflammation, by modulating immune responses.

The study demonstrated that Lck plays a critical role in promoting inflammatory signaling in CD4+ T cells during psoriatic inflammation, suggesting that targeting Lck could be an effective therapeutic strategy for treating psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lck signaling inhibition causes improvement in clinical features of psoriatic inflammation through reduction in inflammatory cytokines in CD4+ T cells in imiquimod mouse model. Al-Harbi, NO., Ahmad, SF., Almutairi, M., et al.[2022]

This study found that MSK1 is significantly activated in lesional psoriatic skin, indicating its potential role in the inflammatory processes associated with psoriasis.

In cultured human keratinocytes, reducing MSK1 expression led to a notable decrease in the production of key pro-inflammatory cytokines (IL-6, IL-8, and TNF-alpha), suggesting that MSK1 could be a target for therapeutic intervention in psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitogen- and stress-activated protein kinase 1 is activated in lesional psoriatic epidermis and regulates the expression of pro-inflammatory cytokines. Funding, AT., Johansen, C., Kragballe, K., et al.[2022]

Tildrakizumab, a monoclonal antibody targeting the IL-23p19 subunit, showed significant clinical improvement in patients with moderate-to-severe psoriasis, with all subjects achieving a 75% reduction in PASI scores by day 196 in the 3 and 10 mg/kg groups.

In a phase I study involving multiple doses, a majority of subjects (10 out of 15 in the 3 mg/kg group and 13 out of 14 in the 10 mg/kg group) achieved PASI75 by day 112, confirming the efficacy of specific IL-23 inhibition in reducing psoriasis severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical improvement in psoriasis with specific targeting of interleukin-23. Kopp, T., Riedl, E., Bangert, C., et al.[2019]

This study found increased activation of MSK2 and CREB in lesional psoriatic skin, suggesting that these proteins may contribute to the development of psoriasis, as evidenced by phospho blotting and immunofluorescence staining.

The research indicates that the p38-MAPK/MSK1/MSK2 and CREB signaling pathway is involved in psoriasis, as activation of this pathway in keratinocytes was inhibited by a p38 inhibitor, highlighting a potential target for therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitogen- and stress-activated protein kinase 2 and cyclic AMP response element binding protein are activated in lesional psoriatic epidermis. Funding, AT., Johansen, C., Kragballe, K., et al.[2022]

Three tyrosine kinase inhibitors from the tyrphostin family effectively halted the growth of psoriatic keratinocytes in laboratory studies without causing harmful cytotoxic effects.

The inhibitors' effectiveness in stopping keratinocyte proliferation correlates with their ability to block EGF receptor kinase activity, suggesting they could be promising new treatments for psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyrphostins suppress the growth of psoriatic keratinocytes. Ben-Bassat, H., Vardi, DV., Gazit, A., et al.[2019]

In a phase IIIb study involving 119 patients with moderate-to-severe plaque psoriasis, guselkumab was significantly more effective than fumaric acid esters (FAE), achieving a PASI 90 response in 82% of patients compared to only 14% for FAE at week 24.

Guselkumab also had a better safety profile, with a lower incidence of adverse events (73% vs. 98% for FAE) and no patients discontinuing treatment due to side effects, highlighting its potential as a safer option for systemic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guselkumab is superior to fumaric acid esters in patients with moderate-to-severe plaque psoriasis who are naive to systemic treatment: results from a randomized, active-comparator-controlled phase IIIb trial (POLARIS). Thaçi, D., Pinter, A., Sebastian, M., et al.[2021]

Citations

1. investors.alumis.com investors.alumis.com/news-releases/news-release-details/late-breaking-esk-001-phase-2-ole-data-presented-2025-aad-annual?mobile=1&mobile=1

Late-Breaking ESK-001 Phase 2 OLE Data Presented at 2025 ... These data demonstrated that patients receiving 40 mg twice daily dosing of ESK-001 achieved long-term sustained or increasing clinical responses through Week ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40659116/

Highly selective, allosteric inhibition of TYK2 with oral ESK ... ESK-001 demonstrated significant dose-dependent improvement in signs and symptoms of psoriasis while achieving continuous target inhibition at the highest dose.

3. alumis.com alumis.com/file.cfm/18/docs/aad2025_pstr_pro_final.pdf

Patient-Reported Outcomes in the Phase 2 Studies of ESK- ... Longer ESK-001 treatment in OLE study resulted in substantially increased PASI and sPGA response rates, while maintaining the improved quality ...

4. conferences.medicom-publishers.com conferences.medicom-publishers.com/content/conference-reports/excellent-long-term-data-for-tyk2-inhibitor-esk-001-in-psoriasis/

Excellent long-term data for TYK2 inhibitor ESK-001 in psoriasis In terms of efficacy, PASI rates increased with longer-term use of ESK-001, with PASI75, PASI90, and PASI100 rates of 77.5%, 61.3%, and 38.8% at ...

5. hcplive.com hcplive.com/view/twice-daily-esk-001-treatment-for-psoriasis-leads-majority-achieving-pasi-75

Twice-Daily ESK-001 Treatment for Psoriasis Leads to ... The interim data suggest that the drug resulted in dose-dependent, sustained improvements in participants' Psoriasis Area and Severity Score ( ...

6. alumis.com alumis.com/file.cfm/18/docs/alumis_pub_2_for_website_aad_pres_vf.pdf

Efficacy and Safety of ESK-001, a Highly Selective Oral ... Safety data displayed based on 8 December 2023 data cut of ongoing OLE study. ... and support continued Phase 3 development of ESK-001 in plaque psoriasis.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11602527/

Safety, tolerability, pharmacokinetics, and pharmacodynamics ... Being well‐tolerated and exhibiting clear PK/PD characteristics, ESK‐001 offers further clinical development as treatment for TYK2‐mediated ...

8. alumis.com alumis.com/file.cfm/18/docs/aad2025_blauvelt_et_al_esk-001_52w_ole_vf.pdf

ESK-001, a Highly Selective Oral TYK2 Inhibitor: 52-Week ... Data are based on the safety analysis population (all treated patients). Safety data displayed are based on 06 SEP 2024 data cut of ongoing OLE study.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06846541

Long-term Safety and Efficacy of ESK-001 in Moderate to ... The objective of the ESK-001-018 long term extension is to evaluate the safety and efficacy of ESK-001 over time. The scientific questions it aims to answer ...

10. alumis.com alumis.com/file.cfm/18/docs/eadv_late_breaker_presentation_final.pdf

Efficacy and Safety of ESK-001, a Highly Selective Oral ... Safety data displayed based on 1 March 2024 data cut of ongoing OLE study. TEAE: treatment emergent adverse event. As of May 31, 2024, there were 6 SAEs ...