Netakimab — new IL-17а inhibitor: 12-week results of phase III clinical study BCD-085-7/PLANETA in patients with moderate-tosevere plaque psoriasis

Abstract

Netakimab, the original monoclonal antibody against IL-17A, is an innovative drug for the treatment of moderate-to-severe plaque psoriasis in patients who have indications for systemic therapy or phototherapy. Netakimab was approved in Russian Federation, registration certificate number ЛП-005439 from 04.04.2019. This article outlines the first 12-week results of a phase III clinical trial in patients with psoriasis.Materials and methods. The BCD-085-7 study (PLANETA) is a comparative, randomized, double-blind, placebo-controlled phase 3 clinical study of the efficacy and safety of netakimab in patients with moderate-to-severe plaque psoriasis. This review presents the results of the first 12 weeks. The study is ongoing at the moment, the total duration of treatment for each patient is 3 years (154 weeks). Patients were randomized in a ratio of 2:2:1 into one of three arms: group 1 received netakimab subcutaneously at a dose of 120 mg once a week for the first three weeks (induction) and then once every 2 weeks up to week 10, group 2 received netakimab subcutaneously at a dose of 120 mg once a week for the first three weeks (induction) and then once every 4 weeks up to week 10, group 3 received a placebo subcutaneously on day 1 at weeks 0, 1, 2, 4, 6, 8 10. In order to maintain a double-blind design, placebo was administered to patients in group 2 at weeks 4 and 8.Results. Both netakimab groups showed a significant superiority over placebo (p < 0.001) and the absence of statistically significant differences between the two regimens of therapy (p > 0.05) across all endpoints. PASI 75 at week 12 was reached by 77.65 % of patients using netakimab once every 2 weeks and 83.33 % of patients using netakimab once every 4 weeks (ITT population). The rate of clear and almost clear skin (sPGA 0–1) was reached by 81.18 and 79.76 % of patients using netakimab once every 2 weeks and once every 4 weeks, respectively. The safety assessment showed no statistically significant differences between the groups, the incidence rate of adverse events in netakimab arms was not higher than in the placebo arm. There were no cases of early withdrawal due to adverse events and cases of grade 4 toxicity according to CTCAE 4.03. During the 12 weeks of the study, one serious adverse event was registered in group 2 (pneumonia grade 3), which was recovered without any consequences. The immunogenicity assessment showed binding antibodies formation at week 12 in one patient who received BCD-085 every 2 weeks. Neutralizing antibodies were not detected. Conclusion. Netakimab showed high efficacy in the treatment of psoriasis, more than 80 % of patients achieved PASI 75 and sPGA 0–1 (clear and almost clear skin) by the week 12 of treatment. The drug showed a favorable safety profile and low immunogenicity. Based on the study results the regimen once a week during the first 3 weeks (induction), then once every 4 weeks was chosen for medical use in patients with psoriasis.

Latest Advances for the Treatment of Chronic Plaque Psoriasis with Biologics and Oral Small Molecules

“…Preliminary results of BCD-085-7/PLANETA study (NCT03390101), a comparative, randomized, double-blind, placebo-controlled phase III clinical study, showed that at week 12 PASI75 was achieved by 83.3% and 77.7% of the patients treated with netakimab 120 mg every four and every two weeks, respectively, compared to 0% in placebo arm. 15–17 The drug showed a favorable safety profile consistent with those expected for the class of IL-17 inhibitors, and low immunogenicity. 15 Finally, the results of the 24-week period phase III clinical trial (PATERA study) investigating the efficacy and safety of netakimab compared to placebo in patients with active psoriatic arthritis showed that netakimab 120 mg is significantly superior to placebo in patients with active psoriatic arthritis.…”

“… 15–17 The drug showed a favorable safety profile consistent with those expected for the class of IL-17 inhibitors, and low immunogenicity. 15 Finally, the results of the 24-week period phase III clinical trial (PATERA study) investigating the efficacy and safety of netakimab compared to placebo in patients with active psoriatic arthritis showed that netakimab 120 mg is significantly superior to placebo in patients with active psoriatic arthritis. In this study PASI75, PASI90 and PASI100 were reported as secondary endpoints ( Table 1 ).…”

Efficacy of netakimab in key psoriatic arthritis domains: 54-week results from the phase III BCD-085-8/PATERA study

“…Профиль безопасности 54 недель применения НТК у пациентов с ПсА соответствовал профилям безопасности НТК при применении у пациентов с псориазом и анкилозирующим спондилитом [8,9]. В большинстве случаев НЯ были не связаны с активной терапией, по мнению исследователей, и имели легкую и среднюю степени тяжести.…”

“…Нетакимаб (НТК) -оригинальное рекомбинантное гуманизированное моноклональное IgG1 антитело против ИЛ-17А. В исследованиях III фазы у пациентов с бляшечным псориазом (BCD-085-7/PLANETA, NCT03390101) и анкилозирующим спондилитом (BCD-085-5/ASTERA, NCT03447704) установлено превосходство НТК над плацебо, а также долговременная эффективность и безопасность препарата [8,9]. BCD-085-8/ PATERA -клиническое исследование (КИ) III фазы, направленное на определение эффективности и безопасности применения НТК у пациентов с активным ПсА (NCT03598751).…”

Successful use of Netakimab in the treatment of psoriasis accompanied by the psoriatic onychodystrophy

“…Так, к 12-й нед. терапии нетакимабом в зарегистрированном режиме дозирования среднее снижение проявлений ониходистрофии составило 52% относительно исходных значений [55].…”