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The current dermatology pipeline includes a wide range of medication classes, from Janus kinase (JAK) inhibitors to tumor necrosis factor inhibitors, to phototherapeutics. At the 2023 American Society of Health-System Pharmacists (ASHP) Summer Meetings and Exhibition,¹ Courtney Queen, PharmD, CSP, of the University of Kentucky Specialty Pharmacy and Infusion Services in Lexington, Kentucky, shared a quick snapshot of some of that pipeline. Although only 4 conditions were covered—chosen due to the high number of agents in the pipeline—Queen noted that “there are so many more [drugs] we could talk about.”

Alopecia Areata

Characterized by circular bald patches on the scalp and body, alopecia areata is a common autoimmune condition. “Several of the drugs in the pipeline to treat [alopecia areata] are JAK inhibitors,” said Queen, a class of medication where the benefits need to be clearly balanced with concerns around the therapies’ black box warnings for heart-related events such as heart attack, blood clots, and stroke. “Many of these new therapies…are more selective JAK inhibitors, and so we are hopeful that some of those [warnings] wouldn’t carry forward,” Queen said. “But I do think the majority of our products will continue to carry that same black box warning and concern.”

Ritlecitinib

This JAK3 and tyrosine kinase inhibitor is under FDA review for adults and adolescents aged 12 years and older living with alopecia areata with 50% or greater scalp hair loss. Ritlecitinib would be a once-daily therapy available in 30 mg and 50 mg doses.

Results of the randomized, placebo-controlled ALLEGRO 2b/3 clinical trial (NCT03732807) demonstrated significantly higher proportions of patients in the treatment group who achieved a Severity of Alopecia Tool (SALT) score ≤20 response by week 20. The drug also met secondary endpoints, including a change from baseline in Depression Subscale Score and Hospital Anxiety and Depression Scale. “This is important for alopecia patients because they also carry a lot of comorbid conditions—sometimes anxiety, sometimes depression—because of their disease state,” Queen explained.

One of the advantages of ritlecitinib is the “diversity in indication,” said Queen; the drug’s indication includes use in children as young as 12 years of age. The drug will primarily be a competitor to baricitinib (Olumiant), an oral JAK 1/2 inhibitor currently only approved for use in adults. However, Queen noted, research is underway evaluating baricitnib in a younger patient population.

If approved, ritlecitinib may come with some challenges around prior authorization. Queen anticipates that payers will require health care providers to trial less expensive medications—"even if those are off label,” she explained, such as oral corticosteroids or topical immunotherapies. She also expects that coverage will be limited to patients with disease involvement of at least 50% of the scalp who are currently experiencing a disease flare of 6 months or longer.

It is anticipated that ritlecitinb will carry the same boxed warning as other medications in the JAK inhibitor class.

Other Notable Pipeline Products

Queen highlighted 3 additional products in the alopecia areata pipeline. CTP-543 (deuruxolitinib), a deuterium-modified form of ruxolitinib, an oral JAK 1/2 inhibitor, is currently in phase 3 clinical research. Anticipated approval is 2024, although this may be delayed after a partial hold was put in place following the development of a pulmonary embolism in 1 patient.

APD334 (etrasimod) is a sphingosine 1-phosphate (S1P) receptor modulator in Phase 2 research, with possible indications for alopecia areata, ulcerative colitis, Crohn’s disease, atopic dermatitis, and eosinophilic esophagitis.

SHR0302 (ivarmacitinib) is a selective JAK 1 inhibitor with possible indications for alopecia areata, ulcerative colitis, and Crohn’s disease, with approval anticipated in 2025.

Atopic Dermatitis

Pharmacists should be familiar with atopic dermatitis, a chronic inflammatory skin condition associated with patches of dry skin, itching, rash, and skin pain, as well as thickening of the skin over time. First-line treatments for mild atopic dermatitis include topical corticosteroids, available in cost-effective generic forms; second-line topical treatments are newer and only available as brand-name products.

For patients with moderate to severe atopic dermatitis, phototherapy is recommended with systemic treatment such as dupilumab. However, competition is on the horizon, as more than a dozen therapies are currently in the pipeline.

Recent Atopic Dermatitis Approvals

One of the most recent approvals for atopic dermatitis is abrocitinib (Cibinqo), an oral JAK-1 inhibitor for moderate to severe atopic dermatitis. In early 2023, abrocitinib received an expanded approval to include patients aged 12 years and older.

Label expansions were recently granted to upadacitinib (Rinvoq), JAK-1 inhibitor; dupilumab (Dupixent), an IL-4 receptor a-antagonist; and tralokinumab (Adbry), an IL-13 antagonist.

Lebrikizumab

Lebrikizumab is another IL-13 antagonist with a target indication for adults and adolescents aged 12 years and up with moderate to severe atopic dermatitis. There are 5 ongoing clinical trials: monotherapy studies ADvocate 1 and ADvocate 2 (NCT04146363 and NCT04178967); combination therapy ADhere (NCT04250337) evaluating lebrikizumab plus topical corticosteroids; adolescent open-label safety study ADore (NCT04250350); and long-term extension study ADjoin (NCT04392154).

Efficacy results of ADvocate 1 and 2 demonstrated that 43% and 33% of patients in the treatment group achieved Investigator’s Global Assessment (IGA) 0 or 1 at 16 weeks, vs 13% and 11% in the placebo group; similarly, 59% and 51% of patients in the treatment group in these trials achieved an Eczema Area and Severity Index (EASI)-75 response at 16 weeks (vs 16% and 18% with placebo). Approval for lebrikizumab is anticipated in Q3 of 2023.

Lebrikizumab would represent competition for tralokinumab and dupilumab, potentially offering a less frequent dosing regimen at every 4 weeks. Investigators may also seek label expansions for patients previously treated with dupilumab, and for patients aged 6 months to 18 years of age.

Challenges around prior authorizations may arise, though, potentially requiring patients to trial topical corticosteroids, crisaborole (Eucrisa), or ruxolitinib (Opzelura); dupilumab may remain the preferred agent.

The Atopic Dermatitis Pipeline

Other treatments in the atopic dermatitis pipeline include IL-31 antagonist nemolizumab, a subcutaneous therapy for moderate to severe atopic dermatitis, anticipated for approval in 2024. The next 12 months may also bring approvals for phosphodiesterase-4 (PDE4) inhibitor roflumilast (Zoryve) and aryl hydrocarbon receptor (AhR) agonist tapinarof (Vtama). “[These drugs] both carry a unique benefit in that they don’t contain a corticosteroid, so they do not have limitations on the duration of treatment, or on what area of the body they can be used on,” Queen noted.

Baricitinib was being evaluated for label expansion to moderate to severe atopic dermatitis, but may not be pursued further after manufacturer Eli Lilly/Incyte received a complete response letter from the FDA.

Plaque Psoriasis

Deucravacitinib (Sotyktu), a tyrosine kinase 2 (TYK2) inhibitor is a first-of-its-kind therapy approved for moderate to severe plaque psoriasis in adults. “It was a groundbreaking [approval],” Queen said. “We like when we have a new target, a new way to treat our patients.” As an oral tablet, deucravacitinib “provides an advantage for patients who have concerns with injection medications,” she added.

Two PDE4 inhibitors are also in the pipeline for label expansions: apremliast (Otezla) for expansion to moderate to severe plaque psoriasis in pediatric patients and for genital psoriasis; and roflumilast (Zoryve) for expansion to patients aged 2 to 11 years.

Bimekizumab

Bimekizumab is an IL-17F and IL-17A antagonist for adults with moderate to severe plaque psoriasis. “It’s a little different than the other [therapies] that we currently have approved in the space,” Queen said, citing its ability to target IL-17F. Approval is anticipated in Q2 of 2023 following a slight delay and resubmission due to a complete response letter issued in 2022.

“I think it’s interesting that there are some head-to-head trials for this medication,” Queen said. Three trials—BE VIVID (NCT03370133), BE SURE (NCT03412747), and BE RADIANT (NCT03536884)—are head-to-head trials with ustekinumab (Stelara), adalimumab (Humira), and secukinumab (Cosentyx), respectively. In all 3 of these trials, treatment with bimekizumab demonstrated superiority in Psoriasis Area and Severity Index (PASI)-90 and IGA endpoints vs all 3 currently approved treatment options.

The Plaque Psoriasis Pipeline

Other notable products for psoriasis include ARQ-154 (roflumilast), a PDE-4 inhibitor topical foam for seborrheic dermatitis, and new formulations of IL-17A receptor antagonist secukinumab including intravenous administration and administration via 300 mg autoinjector.

Spesolimab-sbzo (Spevigo) is an IL-36 receptor antagonist for generalized pustular psoriasis flares, and with its approval became the first IL-36 receptor antagonist on the market.

Epidermolysis Bullosa

This rare, inherited connective tissue disorder causes abnormalities in the cohesion of the layers of the epidermis, including blisters, erosions, and nonhealing ulcerations. “Previously, our disease management was mostly supportive,” said Queen, “but there has been a recent gene therapy approved for this indication.”

Beremagene Geperpavec

Approved on May 19, 2023, beremagene geperpavec (B-VEC; Vyjuvek) is herpes-simplex virus type 1 (HSV-1) vector-based gene therapy formulated as a re-dosable topical gel for patients with dystrophic epidermolysis bullosa with mutations in the collagen type VII alpha 1 chain (COL7A1) gene. Results of the randomized controlled, double-blind GEM-3 clinical trial (NCT04491604) evaluating the efficacy of B-VEC in 31 patients aged 6 months and older with recessive or dominant disease showed that 67% of patients with B-VEC treated wounds achieved the primary endpoint of complete wound healing at weeks 22 and 24 or weeks 24 and 26.

As an orphan drug for this rare disease, B-VEC is the first FDA-approved treatment for epidermolysis bullosa. This therapy can only be administered in a clinic setting or at home by a health care professional.

Reference

1. Rim M, Queen C, Huffmyer M. Specialty pharmacy pipeline updates II: Emerging therapies for complex conditions. Presented at: American Society of Health-System Pharmacists Summer Meetings and Exhibition; June 10-14, 2023; Baltimore, MD.

[This article was originally published by our sister publication, Drug Topics.]