Tremfya (Guselkumab), First-in-Class IL-23 Blocker, Approved for the Treatment of Patients with Moderate-to-Severe Plaque Psoriasis

March 2018, Vol 11, Ninth Annual Payers' Guide - FDA Approvals, News & Updates
Loretta Fala
Medical Writer

Psoriasis affects approximately 7.5 million people in the United States.1,2 Plaque psoriasis is the most common form of psoriasis, affecting 80% to 90% of patients.1 Patients with plaque psoriasis typically have raised red patches that are covered with a silvery white accumulation of dead skin cells.3 Closely monitored medical care is often required to treat the pruritus, pain, and, in some cases, bleeding of psoriatic patches.4

Severe cases of psoriasis can lead to disfigurement and disability.4 Furthermore, patients with psoriasis are at increased risk for psoriatic arthritis, cardiovascular disease, stroke, hypertension, type 2 diabetes, metabolic syndrome, eye disorders, and obesity,4,5 as well as for other autoimmune diseases (ie, celiac disease and Crohn’s disease); Parkinson’s disease; kidney disease; and some types of cancer, including lymphoma and nonmelanoma skin cancer.5,6 Psoriasis can also affect patients’ self-esteem and lead to depression and social isolation.5,6

Treatments for plaque psoriasis include topical therapies; phototherapy; and systemic medications, including retinoids, methotrexate, cyclosporine, biologic therapies, and other agents.5 The interleukin (IL)-23 cytokines play a role in the inflammatory and immune responses in the pathogenesis of psoriasis.7,8

Tremfya First Biologic IL-23 Blocker Approved for Plaque Psoriasis

On July 13, 2017, guselkumab (Tremfya; Janssen), an IL-23 blocker, received US Food and Drug Administration (FDA) approval for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.7,9

The FDA granted guselkumab an expedited regulatory review for this indication.9 Guselkumab is the first FDA-approved biologic therapy that inhibits IL-23.9

Mechanism of Action

Guselkumab is a human G1 lambda monoclonal antibody that selectively binds to a subunit of IL-23, thereby inhibiting its interaction with the IL-23 receptor. By blocking IL-23, guselkumab inhibits the release of pro­inflammatory cytokines and chemokines that play a role in plaque psoriasis.7

Dosing and Administration

The recommended dosage of guselkumab is 100 mg administered by subcutaneous injection at week 0, week 4, and every 8 weeks thereafter. It is available as a 100-mg/mL injection in a single-dose prefilled syringe.7

Key Clinical Trials

The FDA approval of guselkumab was based on results from 3 randomized, double-blind, phase 3 clinical trials—VOYAGE 1, VOYAGE 2, and NAVIGATE.7-11 All 3 studies included patients aged ≥18 years with moderate-to-severe plaque psoriasis who were eligible to receive systemic therapy or phototherapy.7

VOYAGE 1 and 2 randomized 1443 patients with moderate-to-severe plaque psoriasis to receive guselku­mab (100 mg at weeks 0 and 4 and every 8 weeks thereafter), placebo, or adalimumab (Humira; 80 mg at week 0 and 40 mg at week 1, followed by 40 mg every other week thereafter).7

Both studies evaluated the responses at week 16 compared with placebo for the 2 co-primary end points: the proportion of patients who achieved an Investigator’s Global Assessment (IGA) score of 0 (cleared) or 1 (minimal), and those who achieved at least a 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI) composite score (PASI 90).7,8,10 In both studies, guselkumab demonstrated significant superiority over placebo at week 16 (Table 1).7,8,10

Table 1

In addition, a comparison of guselkumab and adalimumab based on the proportion of patients who achieved an IGA score of 0 or 1 at week 16 and at week 24 showed that guselkumab was superior to adalimumab (Table 2).7

Table 2

Other outcome measures included improvement in psoriasis symptoms (eg, itch, pain, stinging, burning, and skin tightness), and improvements in psoriasis of the scalp at week 16.7 In both studies, improvement in psoriasis symptoms at week 16 was greater with guselkumab than with placebo, and more patients who received guselkumab achieved a Psoriasis Symptoms and Signs Diary symptom score of 0 (symptom-free) at week 24 than patients receiving adalimumab.7

The NAVIGATE study evaluated guselkumab efficacy at 24 weeks in 268 patients who did not respond adequately to ustekinumab (Stelara), defined as an IGA score of ≥2 at week 16 after initial treatment. Of these 268 patients, 31% of patients achieved an IGA score of 0 or 1 after guselkumab treatment, with a ≥2 grade improvement at week 28 compared with 14% of patients using ustekinumab, 12 weeks after randomization.7,11

Adverse Reactions

The most common (≥1%) adverse reactions associated with guselkumab therapy in VOYAGE 1 and 2 included upper respiratory infections (14.3%), headache (4.6%), injection-site reactions (4.5%), arthralgia (2.7%), diarrhea (1.6%), gastroenteritis (1.3%), tinea infections (1.1%), and herpes simplex infections (1.1%).7

Elevated liver enzyme levels were more common in patients receiving guselkumab (2.6%) than in those receiving placebo (1.9%).7

Similar to other therapeutic proteins, guselkumab has the potential for immunogenicity. Approximately 6% of patients who received guselkumab had antidrug antibodies up to week 52.7

Guselkumab has no contraindications.7

Drug Interactions

Patients who receive guselkumab and concomitant cytochrome P450 substrates, particularly substrates with a narrow therapeutic index, may need to be monitored for therapeutic effect or drug concentration, and dosage adjustments may be required.7

Use in Specific Populations

Data are not available on the presence of guselkumab in human milk or its effects on the breastfed infant or on milk production. The mother’s clinical need for guselkumab and the health benefits of breastfeeding should be weighed against the potential adverse effects on the breastfed infant from guselkumab or from the mother’s underlying condition.7

In clinical trials, the number of patients aged ≥65 years was insufficient to establish whether their response to guselkumab is different from that of younger patients. Of the 1748 patients who received guselkumab, 93 patients were aged ≥65 years and 4 patients were aged ≥75 years; of these patients, no overall differences were reported between patients aged >65 years and younger patients.7

Warnings and Precautions

Guselkumab is associated with an increased risk for infection. Patients should get medical help if they have signs or symptoms of infection.

If a patient has a serious infection, the patient should be monitored closely, and guselkumab should be discontinued until the infection resolves.7

Patients should be evaluated for tuberculosis before starting guselkumab treatment; guselkumab should not be used in patients with active tuberculosis. For patients with a history of active or latent tuberculosis, antituberculosis therapy should be considered before initiating guselkumab therapy.7

Before patients begin treatment with guselkumab, consideration should be given to completing age-appropriate, guideline-recommended immunizations. Live vaccines should be avoided in patients who receive guselkumab.7

Conclusion

The FDA approval of guselkumab introduced the first IL-23 blocker for the treatment of adults with moderate-­to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Guselkumab selectively inhibits IL-23, a cytokine that plays a role in the inflammation associated with plaque psoriasis. In clinical trials, treatment with guselkumab demonstrated significantly superior efficacy compared with adalimumab in patients with moderate-to-severe plaque psoriasis. In addition, in patients who did not achieve an adequate response with ustekinumab showed significant improvement after receiving guselkumab.

References
1. American Academy of Dermatology. Psoriasis. www.aad.org/media/stats/conditions/psoriasis. Accessed September 6, 2017.
2. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70:512-516.
3. National Psoriasis Foundation. Plaque psoriasis. www.psoriasis.org/about-psoriasis/types/plaque. Accessed September 5, 2017.
4. National Psoriasis Foundation. Psoriasis and comorbid conditions issue brief. www.psoriasis.org/sites/default/files/advocacy/PsoriasisandComorbidConditionsIssueBriefonepager20140225.pdf. Accessed September 6, 2017.
5. Mayo Clinic staff. Psoriasis. www.mayoclinic.org/diseases-conditions/psoriasis/­symptoms-causes/dxc-20317579. Accessed September 5, 2017.
6. National Psoriasis Foundation. Comorbidities associated with psoriatic disease. www.psoriasis.org/about-psoriasis/related-conditions. Accessed September 5, 2017.
7. Tremfya (guselkumab) injection [prescribing information]. Horsham, PA: Janssen Biotech; July 2017.
8. Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76:418-431.
9. Johnson & Johnson. Janssen announces U.S. FDA approval of TREMFYA (guselkumab) for the treatment of moderate to severe plaque psoriasis. Press release. July 13, 2017. www.jnj.com/media-center/press-releases/janssen-announces-­us-fda-approval-of-tremfya-guselkumab-for-the-treatment-of-moderate-to-severe-­plaque-psoriasis. Accessed August 10, 2017.
10. Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76:405-417.
11. Langley RG, Tsai TF, Flavin S, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial. Br J Dermatol. 2018;178:114-123.

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