Izokibep

Clinical efficacy in multiple autoimmune diseases

Izokibep is being developed together with our partners ACELYRIN and Inmagene Biopharmaceuticals as a best-in-class treatment for several autoimmune diseases which arise when the patient’s immune system starts attacking healthy tissue in the body. Izokibep addresses autoimmune diseases that are driven by the protein IL-17. Izokibep has a unique ability to reach the affected tissues, where it binds IL-17 selectively and with high affinity – 10 to 100 times stronger than the current leading IL-17 inhibiting antibody drugs.

The development program for izokibep, which has generated compelling efficacy and safety data, has been progressively extended to multiple indications – a good example of the company’s ability to balance the risks inherent in drug development. Izokibep has already been studied in more than 1,000 patients, in some for as long as three years.

Izokibep in psoriatic arthritis

Psoriatic arthritis (PsA) occurs in patients with psoriasis whose condition develops to include inflammation of the joints. Such patients are currently treated with NSAIDs or immunosuppressive drugs such as TNF and JAK inhibitors.

In March 2024, ACELYRIN reported positive top-line results for izokibep in a Phase 2b/3 clinical study in patients with PsA. The study is a global, double-blind, placebo-controlled, trial comprising 351 patients. The primary endpoint of ACR50 at 16 weeks versus placebo was met with high statistical significance. Robust clinical responses were also achieved for ACR70, PASI100, as well as composite endpoints ACR50/PASI100 and Minimal Disease Activity. Izokibep was well-tolerated with a favorable safety profile consistent with previous experience and the IL-17 class. The study is continuing up to 52 weeks. ACELYRIN expects this Phase 2b/3 trial to be the first of two registrational trials in PsA. A confirmatory Phase 3 study with izokibep in PsA is expected to start during 2024.

In a previous Phase 2 double-blind, placebo-controlled, 16-week study comprising 135 patients, izokibep showed a higher efficacy than that which has been reported in studies with current standard treatments, as well as a favorable tolerability profile. In-depth analyses investigating the clinical benefit of treatment with izokibep showed substantial improvements in key manifestations, including arthritis, psoriasis, enthesitis, dactylitis, and nail psoriasis. Improvements were also found across all studied patient reported symptom categories, including pain, sleep disturbance, physical function, and coping. The treatment with izokibep continued for up to 46 weeks with continued and marked improvements in key manifestations of disease. Izokibep was generally well-tolerated – in line with previous trials with izokibep.

Izokibep in hidradenitis suppuratia

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that affects hair follicles in skin areas with a high concentration of sweat glands. The disease produces recurrent painful varicose ulcers, mainly in the armpits, groin, and the area around the anus. The treatment consists mainly of analgesics, antibiotics, and, in severe cases, surgery and/or biologics.

Izokibep is currently being evaluated in a Phase 3 study comprising approximately 250 patients suffering from HS. Topline data are expected in the second half of 2024. ACELYRIN plans an additional Phase 3 trial in HS of approximately 400 patients to address FDA guidance on size of safety database.

Open-label (Part A) results from a previous Phase 2b HS study demonstrated that a third of patients achieved complete reduction of symptoms already after 12 weeks. In September 2023, our development partner ACELYRIN announced that the primary endpoint of HiSCR75 at 16 weeks was not met in the placebo-controlled part of the Phase 2b study (Part B). Responder discontinuations and a marked increase in placebo rates during the latter part of the study were factors that had a negative impact on the statistical analysis of the primary endpoint. However, a post-hoc sensitivity analysis on the full dataset as well as a pre-specified interim analysis demonstrated statistical significance in favor of izokibep over placebo at 16 weeks.

Long-term 32-week data from an open label extension of the study demonstrated that continued treatment with izokibep led to further clinical improvements over time with maintained favorable safety profile. Patients who switched from placebo to izokibep at week 16 achieved a similar speed and magnitude of response, as those who began treatment with izokibep at baseline.

The totality of these Phase 2b results suggests that the reason for not meeting the primary endpoint was not related to the study drug, izokibep.

Izokibep in uveitis

Uveitis is a rare inflammatory disease that primarily affects the uvea of the eye. It is one of the most common medical causes of blindness. The only approved treatment today is the TNF inhibitor adalimumab (Humira), a drug that has proven ineffective in parts of the patient population – thus creating a large need for efficacious and safe treatment options.

Izokibep is currently being evaluated in a Phase 2b/3 clinical study in patients with non-infectious intermediate uveitis, posterior uveitis, and panuveitis. Topline data are expected in the second half of 2024.

Izokibep in axial spondyloarthritis

Axial spondyloarthritis (axSpA) is an autoimmune disease that affects the spine, as well as joints in other parts of the body. It usually presents before the age of 45 and can lead to severe pain and reduced mobility. Current treatments consist of NSAIDs or immunosuppressive drugs such as TNF and JAK inhibitors. Izokibep is planned to be evaluated in a Phase 3 program in axSpA.

Izokibep in psoriasis

Psoriasis is an autoimmune disease characterized by thickened, reddened, and clearly defined patches in the skin around the knee and elbow joints, on the scalp, or on other parts of the body. The standard treatment of the disease consists of topical treatments and UV-radiation therapy. However, in severe psoriasis, systemic immunosuppressive drugs are used, which may cause adverse effects over time.

Izokibep has been evaluated in a double-blind, placebo-controlled Phase 2 study over 52 weeks in 108 patients diagnosed with moderate to severe psoriasis. The treatment results indicated a competitive efficacy and safety profile. The majority of the reported side effects were minor and resolved during the length of the treatment. The study was extended, and three-year data confirmed the safety, tolerability, and treatment efficacy of izokibep in the patient group that participated in the extension. The study was published in the British Journal of Dermatology (BJD) in September 2023.