Novartis’ Cosentyx gets approval in Japan

Cosentyx approval is based on phase III programme demonstrating high, sustained efficacy in the skin clearance of moderate-to-severe plaque psoriasis

Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Novartis’ Cosentyx (secukinumab, formerly known as AIN457), for the treatment of both psoriasis vulgaris and psoriatic arthritis (PsA) in adults who are not adequately responding to systemic therapies (except for biologics). This approval marks the first country approval for Cosentyx in the world and makes it the first interleukin-17A (IL-17A) inhibitor to receive regulatory approval in either of these indications in Japan.

Cosentyx works by inhibiting the action of IL-17A, a protein that is found in high concentrations in skin affected by psoriasis and central to the development of inflammatory diseases, including psoriasis and PsA[14-19]. As approximately 30 per cent of psoriasis patients are also affected by PsA globally[12], this approval means that these patients in Japan now have a new treatment option that effectively treats both diseases.

In psoriasis clinical trials, 70 per cent of patients achieved clear or almost clear skin within the first 16 weeks of treatment with Cosentyx 300 mg (p<0.0001), which was maintained in the majority of patients up to Week 52 (with continued treatment)[1]. In the PsA trials, Cosentyx demonstrated significant and sustained efficacy versus placebo in improving signs and symptoms of PsA, as measured by a 20 per cent reduction in the American College of Rheumatology response criteria (ACR 20), which is a standard criteria to assess the effectiveness of arthritis treatments. Between 50- 54 per cent of Cosentyx patients achieved at least ACR 20 in two pivotal studies, FUTURE 1 (150 mg; p<0.0001) and FUTURE 2 (150 and 300 mg; p<0.0001)[4],[5].

Psoriasis is a chronic immune-mediated disease characterised by thick and extensive skin lesions, called plaques, known to cause itching, scaling and pain; it is associated with significant impairment of physical and psychological quality of life[6],[20],[21]. Closely linked with psoriasis, PsA causes joint pain and stiffness, skin and nail psoriasis, swollen toes and fingers, persistent painful tendonitis and irreversible joint damage[13]. Up to 40 per cent of people can suffer from joint destruction and permanent physical deformity[22].

This approval was based on the safety and efficacy results from more than 10 phase II and phase III studies which included nearly 4,000 patients with moderate-to-severe plaque psoriasis[1-3],[13] and supported by two pivotal phase III studies, FUTURE 1 and FUTURE 2, involving more than 1,000 patients with PsA[4],[5]. In all studies, Cosentyx demonstrated a favourable safety profile, with similar incidence and severity of adverse events (AEs) between Cosentyx treatment arms (300 mg and 150 mg)[1-5],[23].

US Food and Drug Administration (FDA) approval in the same indication is anticipated in early 2015 following the unanimous recommendation of approval in October 2014 from the Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC) to the US FDA.

References:

[1] Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis: results of two phase three trials. N Engl J Med. 2014. Jul 9;371(4):326-38.
[2] Blauvelt A, Prinz J, Gottlieb AB, et al. Secukinumab Administration by Pre-filled Syringe: Efficacy, Safety, and Usability Results from a Randomized Controlled Trial in Psoriasis (FEATURE). Br J Dermatol. 2014; [published online ahead of print August 16, 2014].
[3] Paul C, Lacour JP, Tedremets L, et al. Efficacy, safety, and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol. 2014; [published online ahead of print September 22, 2014].
[4] Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, improves active psoriatic arthritis and inhibits radiographic progression: efficacy and safety data from a phase 3 randomized, multicenter, double-blind, placebo-controlled study. Oral presentation at: ACR/ARHP Annual Meeting, Boston, MA, USA, 2014. Presentation number 948.
[5] McInnes IB. Secukinumab, a Human Anti-Interleukin-17A Monoclonal Antibody, Improves Active Psoriatic Arthritis: 24-Week Efficacy and Safety Data from a Phase 3 Randomized, Multicenter, Double-Blind, Placebo-Controlled Study Using Subcutaneous Dosing. Oral presentation at: ACR/ARHP Annual Meeting, Boston, MA, USA, 2014. Abstract number: L1.
[6] Stern RS, Nijsten T, Feldman S, et al. Psoriasis Is Common, Carries a Substantial Burden Even When Not Extensive, and Is Associated with Widespread Treatment Dissatisfaction. J Investig Dermatol Symp. 2004;9(2):136-9.Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009; 361(5):496-509.
[12] Gladman DD, Antoni C, Mease P, et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005; 64:ii14-ii17.
[13] American College of Rheumatology (ACR) website. “Spondylarthritis (Spondylarthropathy).”http://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Spondylarthritis_(Spondylarthropathy)/. Accessed December 2013.
[14] Gaffen SL. Structure and signaling in the IL-17 receptor family. Nat Rev Immunol. 2009;9(8):556-67.
[15] Ivanov S, Linden A. Interleukin-17 as a drug target in human disease. Trends Pharmacol Sci. 2009;30(2):95-103.
[16] Kopf M, Bachmann MF, Marsland BJ. Averting inflammation by targeting the cytokine environment. Nat Rev Drug Discov. 2010; 9(9):703-18.
[17] Onishi RM, Gaffen SL. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology. 2010;129(3):311-21.
[18] Krueger J, Fretzin S, Suárez-Fariñas M, et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol. 2012;130(1):145-154.
[19] Johansen C, Usher PA, Kjellerup RB, et al. Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Brit J Dermatol. 2009;160(2):319-24.
[20] Rapp SR, Feldman SR, Exum ML, Fleischer AB, Jr., Reboussin DM. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol. 1999; 41(3 Pt 1):401-7.
[21] Farley E et al. Psoriasis: comorbidities and associations. G Ital Dermatol Venereol. 2011 Feb;146(1):9-15.
[22] Medscape Reference website. “Medical Care in Psoriatic Arthritis.” http://emedicine.
medscape.com/article/331037-overview#a30. Accessed October 2014.
[23] Novartis data on file. 2013: Clinical study reports for CAIN457A2302 [ERASURE] ; CAIN457A2303 [FIXTURE] ; CAIN457A2307 [JUNCTURE] ; CAIN457A2308 [FEATURE].

EP News Bureau – Mumbai