Biologics in Plaque Psoriasis

Abstract


 Health Canada has approved 11 biologics for the treatment of adults with moderate-to-severe plaque psoriasis (PsO). These biologics can be divided into 2 groups based on mechanisms of action and market authorization dates:
 
 Old-generation biologics (5): include anti–tumour necrosis factor (TNF) agents (etanercept, adalimumab, infliximab, and certolizumab pegol) and an anti-interleukin (IL)-12/IL-23 inhibitor (ustekinumab) which were approved in Canada before 2010.
 New-generation biologics (6): include anti-IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) and anti-IL-23 inhibitors (guselkumab, tildrakizumab, and risankizumab) which were approved in Canada in 2015 or later.
 
 
 Patent protection has expired for infliximab, certolizumab, and ustekinumab. There is no valid data protection status for all 5 older generation biologics. However, only 3 of the old-generation biologics have biosimilar versions (adalimumab, etanercept, and infliximab) that are available in the Canadian market.
 
 Biosimilar versions for adalimumab and etanercept were marketed for PsO approximately 3 years to 4 years after their initial Notice of Compliance was issued, respectively. This delay can be attributed to various factors, including litigation and global agreements between manufacturers.
 Despite the expiry of data and patent protection for both ustekinumab and certolizumab, no biosimilar versions are available in Canada. Data protection for both biologics expired more than 4 years ago, and the patents have expired in 2021. A lack of a biosimilar entrant in Canada could be attributed to various factors, including clinical trial development based on exclusivity timelines in the US, where data protection is 4 years longer for biologics versus Canada.
 
 
 CADTH has reviewed 3 of 5 of the old-generation biologics and all 6 of the new-generation biologics; all drugs received similar CADTH Canadian Drug Expert Committee (CDEC) recommendations. The clinical programs of most of the new-generation biologics included direct evidence demonstrating superiority or statistically significantly higher efficacy outcomes compared with the active comparator of the old-generation biologics. The clinical trials for new-generation biologics also incorporated more stringent primary outcome measures.
 The old-generation biologics predated the pan-Canadian Pharmaceutical Alliance (pCPA) process (except for certolizumab), which could imply disparate product listing agreements across public drug plans for these drugs. The only biologics not included on any public formularies are certolizumab, guselkumab, and tildrakizumab (although tildrakizumab has yet to begin pCPA negotiations). Listing status for biologics fell under restricted benefit, but differed in terms of active (e.g., review through special authorization forms) versus passive (e.g., Limited Use codes in Ontario) procedures across public drug plans. Moreover, 3 public drug plans employed 2-tiered formularies (i.e., Alberta, Manitoba, and Correctional Services Canada) which required a trial of new-generation biologics or old-generation biosimilars before reimbursement of old-generation originators.
 Utilization patterns of old- versus new-generation biologics within the Ontario Public Drug Programs demonstrated that a significant proportion of new patients were treated with old-generation biologics (54% in 2019 and 37% in 2020) despite the availability of multiple new-generation biologics.
 In conclusion, formulary management is warranted for biologics for PsO given the significant utilization of old-generation originators in the current context of delayed marketing of their biosimilar versions for PsO and their reimbursement predating the pCPA process. New-generation biologics underwent pCPA negotiations and direct evidence was submitted that demonstrated superiority versus old-generation biologic active comparators, which may ultimately prove to be a greater value for patients and payers.

Formulary Management of Biologics in Plaque Psoriasis

“…In Canada, patent protection is a 20-year period offered to innovative drugs from the date of filing that can be applied in various manners (e.g., chemical, change in use). 24 Data protection regulations in Canada are governed by the Food and Drug Regulations published in 2006. 25,26 These regulations provide data protection for an 8-year term with a possibility of adding 6 more months for submissions that include pediatric studies.…”

“…At the time of the completion of the Environmental Scan (November 2021), Health Canada had approved 11 biologics for the treatment of moderate to severe PsO in adults. 24 Five of these drugs are old-generation biologics (adalimumab, certolizumab pegol, etanercept, infliximab, and ustekinumab) and the remaining 6 drugs (brodalumab, guselkumab, ixekizumab, risankizumab, tildrakizumab, and secukinumab) are new-generation biologics.…”

The Effectiveness of Risankizumab Following Guselkumab Failure in Moderate-to-Severe Psoriasis Patients: A Retrospective Study

“…2,3 Currently, many biologic options are available and approved for the treatment of plaque psoriasis including tumor necrosis factor alpha (TNF-α) inhibitors, interleukin (IL)12/23 inhibitors, IL-17 inhibitors, and IL-23p19 inhibitors. 4 Guselkumab, a human IgG1 monoclonal antibody approved for treatment of moderate-to-severe psoriasis in 2017 and psoriatic arthritis in 2020, selectively targets the p19 subunit of IL-23, leading to the disruption of the type 17 helper-T-cell/IL-17 pathway. 5,6 This pathway is an important regulator of innate and adaptive immunity which is thought to be disrupted in the pathogenesis of plaque psoriasis.…”