Boehringer Ingelheim gets CDSCO panel nod to market Spesolimab indicated for generalized pustular psoriasis
New Delhi: Granting the local clinical trial waiver, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has given the nod to the pharmaceutical major Boehringer Ingelheim to import and market Spesolimab concentrate as a solution for infusion 450 mg/vial indicated for the treatment of generalized pustular psoriasis (GPP).
However, this approval is subject to the condition that the firm should include a reasonable number of patients from India in the global Phase IV study, there should be a screening of patients by the QuantiFERON-TB Gold test for tuberculosis, and positive patients should be excluded from the study.
This was in line with the proposal presented by the drug maker Boehringer Ingelheim for the import and marketing of Spesolimab concentrate for solution for infusion (450 mg/vial) indicated for generalized pustular psoriasis (GPP), with a local clinical trial waiver.
Furthermore, the committee proposed to conduct global Phase IV study including Indian patients.
The committee noted that generalized pustular psoriasis (GPP) is a rare disease and is potentially life-threatening with a pathway of interleukin 36 (IL 36) in its pathogenesis.
Spesolimab is an IL-36 inhibitor and has received orphan drug designation and breakthrough therapy designation for the treatment of GPP in the US. Presently, there is no similar drug therapy available in India, resulting in an unmet medical need. The drug is currently approved in the US, Japan, the EU, China, and Taiwan.
In addition, the expert panel noted that the firm also proposed to conduct a global Phase-IV study, including Indian patients, which would be an open-label safety trial to assess the effect of immunogenicity on pharmacokinetics (PK), safety, and efficacy on re-treatment of flares that occur after the first flare incidence has been treated and resolved in a GPP flare.
Pustular psoriasis is a type of psoriasis, a chronic and recurrent immune-mediated multisystem disorder. Based on the characteristics and distribution of pustules, the disorder has different phenotypes, such as GPP. While the pathophysiology of psoriasis is not fully understood, some pro-inflammatory cytokines involved in the innate and adaptive immune systems have been implicated as key mediators of psoriatic disease.
Interleukin (IL)-36 is one of those cytokines whereby unregulated activation and expression of IL-36, often due to IL36RN gene mutations, can result in pathological autoinflammatory responses in pustular psoriasis. IL-36 is expressed in epithelial and immune cells and has three members, IL-36α, IL-36β, and IL-36γ, that bind to a receptor complex to activate pro-inflammatory and pro-fibrotic downstream signalling pathways, such as increased expression and actions of pro-inflammatory cells and factors. The heterodimeric receptor complex IL-36R comprises an IL-1RL2 subunit - to which IL-36 binds - and an IL-1RAcP co-receptor.
Spesolimab is an interleukin-36 receptor antagonist used to treat generalized pustular psoriasis flares in adults. The exact mechanism of action of spesolimab in managing psoriatic flares is unclear; however, it is believed to ameliorate inflammation by inhibiting IL-36 signaling. Spesolimab binds to the IL-36R receptor complex, preventing the binding of IL-36 and the downstream activation of receptor signaling pathways.
At the recent SEC meeting for Dermatology & Allergy held on the expert panel on February 15, 2023, the expert panel reviewed the proposal presented by Boehringer Ingelheim for the import and marketing of Spesolimab concentrate for solution for infusion 450 mg/vial, indicated for generalized pustular psoriasis (GPP).
After detailed deliberation, the committee recommended the grant of permission to import and market Spesolimab concentrate as a solution for infusion at 450 mg per vial for the treatment of flares in adult patients with generalized pustular psoriasis (GPP), subject to the following conditions:
i. The global Phase IV study should include a reasonable number of patients from India.
ii. There should be a screening of patients by the QuantiFERON-TB Gold test for tuberculosis, and positive patients should be excluded from the study.
Accordingly, the expert panel requested the firm to submit the global Phase IV clinical trial protocol within 3 months of obtaining import and marketing permission.
