New options are being developed for conditions including psoriatic arthritis, ulcerative colitis, and asthma.
Immunology drugs represent a significant portion of the current new drug pipeline and are forecasted as a key area of growth for specialty pharmacy. At the 2022 American Society of Health-System Pharmacists Summer Meetings & Exhibition,1 held in Phoenix, Arizona, Caitlyn Anne Young, PharmD, a PGY-2 Investigational Drugs and Research Pharmacy Resident at Michigan Medicine in Ann Arbor, shared the latest updates in immunology therapies with a. specific focus on dermatology, gastrointestinal, and respiratory conditions.
Check out our coverage of the 2022 ASHP Summer Meetings and Exhibition to learn more about the latest in the specialty drug pipeline.
Click through for the latest dermatology updates in atomic dermatitis, plaque psoriasis, and psoriatic arthritis.
Abrocitinib (Cibinqo) was FDA approved in January 2022 for the treatment of moderate to severe atopic dermatitis (AD), with a recommendation for use in cases refractory to treatment after biologic therapies and other disease-modifying antirheumatic drugs (DMARDs) have been trialed—making abrocitinib a second-line therapy for the disease.
Data from the JADE clinical trials (NCT03349050, NCT03575871, and NCT03720470), which compared abrocitinib vs placebo and dupilumab (Dupixent). Most notably, Young said, abrocitinib demonstrated rapid control over itch response, a secondary endpoint that is particularly important for patients’ quality of life. Some dose-dependent adverse events were observed, including thrombocytopenia with increased dose levels, she added.
Prior authorization requirements vary, but typically, patients must have tried and failed at least 1 high potency, topical corticosteroid and at least 1 systemic therapy before abrocitinib approval will be granted.
Abrocitinib is available as a once daily 100 mg oral tablet, with a maximum daily dose of 200 mg.
Deucravacitinib is a novel, first-in-class selective oral tyrosine kinase 2 inhibitor for moderate to severe plaque psoriasis with an anticipated FDA approval date of September 2022. The drug inhibits signaling of interleukin (IL)-23, IL-12, and Type 1 interferons, without inhibiting Janus kinase (JAK) 1, 2, or 3.
In clinical the POETYK-PSO1 and POETYK-PSO2 clinical trials (NCT03624127 and NCT03611751, respectively), investigators compared deucravacitinib with placebo and apremilast (Otezla) 30 mg twice daily, which is the current standard of care dosing for moderate to severe plaque psoriasis.
“In terms of its primary and secondary endpoints, [deucravacitinib] performed really, really well,” said Young. “There are really promising outcomes here with no really alarming safety signals.”
Deucfravacitinib is formulated as an oral, once-daily 6 mg tablet.
Bimekizumab (Bimzelx) is another drug aimed at treating moderate to severe plaque psoriasis, with “a little bit of a different mechanism of action compared to the other IL-17 monoclonal antibodies,” said Young. “IL-17 is thought to be pro-inflammatory and heavily involved in in inflammation…compared with [tumor necrosis factor alpha (TNF-a)]. However, IL-17F is also expressed specifically in psoriatic skin lesions.”
Three clinical trials—BE VIVID (NCT03370133), BE SURE (NCT03412747), and BE RADIANT (NCT03536884)—compared bimekizumab with ustekinumab, adalimumab, secukinumab, and, respectively; in all trials, bimekizumab demonstrated superiority in all primary clinical endpoints. However, Young added, “One thing to note is that [bimekizumab] does show much higher rates of oral candidiasis when compared to all different treatment options, so patients will need to be counseled on the potential development of thrush while on this medication.”
In May 2022, the FDA issued a complete response letter indicating that the approval process will be halted until certain preapproval indication criteria are addressed. “Although it was anticipated for possible approval later this year, we may be looking moreso to 2023,” Young added.
Bimekizumab is formulated as a subcutaneous injection and dosed at 320 mg every 4 weeks, with maintenance dosing every 4 to 8 weeks.
“We’re seeing a lot of label expansions happening for currently marketed drugs,” said Young. Two drugs on that list are being investigated for potential label expansions to treat both ulcerative colitis (UC) and Crohn disease: risankizumab (Skyrizi), an IL-23 immunoglobulin 1 (IgG1) monoclonal antibody indicated for moderate to severe plaque psoriasis and psoriatic arthritis (PsA), with a projected 2022 third quarter approval; and guselkumab (Tremfya), another IL-23 IgG1 monoclonal antibody approved for plaque psoriasis and PsA projected to be approved in 2023. Upadacitinib (Rinvoq), a JAK-STAT inhibitor currently also approved for AD, rheumatoid arthritis (RA), and PsA received FDA approval of the label expansion in March 2022.
Other drugs seeking label expansion for GI conditions include golimumab (Simponi), an anti- TNF-a monoclonal antibody for RA, PsA, ankylosing spondylitis, and UC in adults. Approval is being sought for the treatment of UC in children and adolescents aged 2 to 17 and is projected for 2023. Vedolizumab (Entyvio) is an a4b7 integrin inhibitor already approved for UC and Crohn disease; the proposed indication is a subcutaneous formulation for UC therapy slated for 2023.
Ozanimod (Zeposia), a sphingosine 1-phosphate (S1P) receptor modulator for UC and multiple sclerosis, is currently under investigation as a therapy for Crohn disease. This drug rounded out the list, with an projected approval date of 2024.
Young also highlighted 4 GI therapies in the pipeline with projected approval dates in 2023 or 2024: fligotinib (Jyseleca), a JAK1 inhibitor with proposed indications for UC and Crohn disease; etrasimod, a S1P receptor modulator with proposed indications for UC, Crohn disease, and eosinophilic esophagitis; and a4b7 integrin inhibitor etrolizumab and anti-IL-23p19 IgG4 monoclonal antibody mirikizumab, both with proposed indications for UC and Crohn disease.
Of note, said Young: “Etrasimod projected to be the first FDA approved treatment for eosinophilic esophagitis, but just a few weeks ago, dupilumab was granted that indication by the FDA,” which may lead to some delays in the drug’s approval for that particular indication.
“[Respiratory therapies] have been a little bit slower in terms of pipeline development, with only 1 really notable medication that [was] approved late last year,” said Young.
That drug was tezepelumab (Tezpire), an add-on maintenance treatment for asthma in patients age 12 and older, which Young described as “a broad indication compared with other biologic medications in this class.” Rather than using other therapies off-label, first-in-class tezepelumab offers patients an on-label monoclonal antibody option with a novel mechanism of action: it is a thymic stromal lymphopoietin (TSLP) blocker immunoglobulin 2l monoclonal antibody that binds to human TSLP and blocks interaction with the TSLP receptor.
The pivotal NAVIGATOR and PATHWAY trials (NCT03347279 and NCT03054130)demonstrated strong efficacy and safety, with minimal adverse events noted.
Tezepelumab was approved by the FDA in December 2021 and is dosed as a 210 mg subcutaneous injection every 4 weeks; compared with other monoclonal antibodies on the market, it must be administered in a clinic by a health care provider.