Promising Long-term Results for ESK-001 in Psoriasis

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Alumis Inc. has announced promising results from the open-label extension (OLE) of its phase 2 STRIDE clinical trial for ESK-001. The findings were presented during a late-breaking session at the 2024 European Academy of Dermatology & Venereology (EADV) Congress held from September 25 to 29 in Amsterdam, Netherlands.¹

ESK-001 is a highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2), a key target in treating various immune-mediated conditions, including moderate to severe plaque psoriasis. The company stated the drug is currently undergoing evaluation in the phase 3 ONWARD clinical program, which aims to assess its safety and efficacy in a larger patient population.

Encouraging Trial Results

According to a news release, the interim results from the 28-week OLE, as of March 1, 2024, demonstrated sustained improvements in the Psoriasis Area and Severity Score (PASI) among patients. Notably, the release stated that 93% of patients receiving the highest dose of 40 mg twice daily achieved PASI 75, which they noted as significant indicator of treatment effectiveness. When considering modified non-responder imputation (mNRI), the percentage was still impressive at 82.7%. Researchers said these findings suggest that ESK-001 not only delivers quick results but also maintains efficacy over time with ongoing treatment.

“The OLE results continue to show that ESK-001 has the potential to safely and effectively inhibit the TYK2 target at the 40 mg twice daily dose and deliver lasting benefits that improve over time with continued treatment,” said Dr. Jörn Drappa, Alumis’ chief medical officer, in the release. “These data reinforce our confidence in ESK-001’s potential as a best-in-class oral treatment for moderate to severe plaque psoriasis. We look forward to reporting the full 52-week OLE data in the first half of 2025 and continuing to advance ESK-001 in the phase 3 ONWARD clinical program.”

Safety Profile

The safety data from the OLE period indicated that ESK-001 has a favorable safety profile, with treatment-emergent adverse events (TEAEs) being mostly mild to moderate and self-limiting. Researchers wrote that common TEAEs included upper respiratory tract infections, nasopharyngitis, and headaches, with frequencies similar across all study arms. The company noted this safety profile is critical for long-term treatment options, as chronic conditions like psoriasis often require sustained therapy.

Supporting Data and Additional Presentations

In addition to the promising OLE results, Alumis presented several abstracts at the EADV Congress. An oral presentation highlighted biomarker data from the phase 2 STRIDE trial, showing that the 40 mg twice daily dose achieves maximal target inhibition according to biomarker analysis, which aligns with the highest response rates observed.² An e-poster presentation further discussed significant improvements in patient-reported quality of life and reductions in psoriasis-associated pruritus, demonstrating a clear, dose-dependent improvement in overall well-being.³

According to the release, the ongoing phase 3 ONWARD program consists of 2 identical global phase 3 trials, ONWARD1 and ONWARD2. Each trial will involve approximately 840 patients randomized into 3 groups: those receiving ESK-001 at 40 mg twice daily, those receiving placebo, and those receiving apremilast. The co-primary efficacy endpoints will include the proportion of patients achieving PASI 75 and a score of 0/1 on the static Physician's Global Assessment (sPGA) compared to placebo at week 16. Patients who complete week 24 will have the opportunity to participate in a long-term extension trial, ONWARD3, focused on evaluating the durability of response and long-term safety.

Future Directions

The company stated that the promising data from the phase 2 STRIDE trial and the ongoing phase 3 clinical program are paving the way for ESK-001 to potentially become a best-in-class oral treatment for plaque psoriasis. It is also developing a once-daily modified release formulation of ESK-001, which may offer additional convenience and adherence benefits for patients.

Moreover, Alumis is exploring the broader application of ESK-001 in other autoimmune conditions. The drug is currently being evaluated in the LUMUS phase 2b clinical trial for systemic lupus erythematosus, reflecting the company’s commitment to leveraging its precision data analytics platform to identify new therapeutic avenues.

References

1. Late-breaking data at EADV of ESK-001, an oral TYK2 inhibitor for the treatment of psoriasis, demonstrate significant responses with sustained increases over 28 weeks in phase 2 OLE study. News Release. Alumis, Inc. September 27, 2024. Accessed October 1, 2024. https://investors.alumis.com/news-releases/news-release-details/late-breaking-data-eadv-esk-001-oral-tyk2-inhibitor-treatment
2. ESK-001, an allosteric TYK2 inhibitor, downregulates biomarkers of disease and TYK2 activity. Presentation at EADV 2024. Amsterdam, Netherlands. September 25-28, 2024.https://www.alumis.com/file.cfm/18/docs/final_eadv_2024_biomarker_oral_presentation.pdf
3. Patient-reported outcomes in the randomized, double-blind phase 2 study of ESK-001, an oral allosteric TYK2 inhibitor, in adults with moderate to severe plaque psoriasis. Poster presented at EADV 2024. Amsterdam, Netherlands. September 25-28, 2024. https://www.alumis.com/file.cfm/18/docs/eadv_2024_pstr-pro_ole.pdf