Tremfya (Guselkumab), a Novel One-Press Patient-Controlled Injection, Approved for Moderate-to-Severe Plaque Psoriasis

2019 Payers' Guide Mid-Year Addendum - Select Drug Profiles
Loretta Fala
Medical Writer

Psoriasis, a chronic skin disease associated with overactive inflammatory and immune responses, affects more than 8 million people in the United States.1,2 Plaque psoriasis, the most common form of psoriasis, affects between 80% and 90% of people with the condition and is characterized by thick, raised, scaly patches of skin (plaques) that are often painful and itchy.3 Psoriatic plaques can develop anywhere on the skin and appear most often on the elbows, knees, lower back, torso, scalp, and nails.2,3

Psoriatic arthritis affects between 1.3% and 34.7% of patients with psoriasis. In addition, individuals with psoriasis are at an increased risk for comorbidities, including type 2 diabetes, hypertension, cardiovascular disease, kidney disease, eye disorders, and certain autoimmune disorders.4

Psoriasis can have a profound impact on the patient’s social, emotional, and psychological well-being, including depression and suicidal ideation.4 Overall, nearly 60% of patients with psoriasis report that the disease is very problematic in their everyday life, and those with moderate-to-severe disease report the greatest negative impact on their quality of life.1

Current treatments for plaque psoriasis include topical therapies, phototherapy, conventional systemic therapies (acitretin, cyclosporine, and methotrexate), other systemic therapies (an oral phosphodiesterase-4 inhibitor), and biologic therapies (tumor necrosis factor blockers, interleukin [IL]-17A antagonists, IL-23 antagonists, and an IL-12/IL-23 antagonist).4,5 Biosimilar agents—drugs that are very similar to existing biologic therapies approved by the US Food and Drug Administration (FDA), with no clinically meaningful differences—are also available for the treatment of psoriasis.6

Guselkumab One-Press Injector Is Approved

On February 27, 2019, the FDA approved guselkumab (Tremfya; Janssen Biotech), a novel one-press patient-controlled injector for subcutaneous injection, for the treatment of patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.7 Guselkumab, an IL-23 blocker, was initially approved by the FDA in 2017 as a single-dose prefilled syringe, becoming the first IL-23 inhibitor approved for moderate-to-severe plaque psoriasis.8

“The results of the ORION study showed the administration of Tremfya with One-Press was safe and effective, providing patients with a new, more convenient way to inject their treatment,”7 said Laura Ferris, MD, PhD, Associate Professor, Department of Dermatology, University of Pittsburgh Medical Center, and investigator for guselkumab.

Mechanism of Action

Guselkumab is a human immunoglobulin G1 lambda monoclonal antibody that selectively binds to a subunit of IL-23 (a proinflammatory cytokine), thereby inhibiting its interaction with the IL-23 receptor. By blocking IL-23, guselkumab inhibits the release of proinflammatory cytokines and chemokines that are implicated in the pathogenesis of plaque psoriasis.9

Dosing and Administration

Guselkumab is available as a 100-mg/mL injection in a single-dose prefilled syringe or in a single-dose one-press patient-controlled injector.9

The recommended dose of guselkumab is 100 mg, administered by subcutaneous injection at weeks 0 and 4, and every 8 weeks thereafter. Each one-press injector is intended for single-dose only. Patients should be instructed to inject the full amount (1 mL), which provides 100 mg of guselkumab.9

Guselkumab one-press should be administered under the guidance and supervision of a physician. After appropriate training, patients may self-inject with the guselkumab one-press patient-controlled injector.7

Pivotal Clinical Trials

The initial FDA approval of guselkumab in 2017 was based on results from 3 randomized, double-blind, phase 3 clinical trials—VOYAGE 1, VOYAGE 2, and NAVIGATE.9-12 The efficacy and safety of one-press guselku­mab approved in 2019 was demonstrated in the ORION clinical trial, a double-blind, placebo-­controlled phase 3 clinical trial.9,13 All 4 studies included patients aged ≥18 years with moderate-to-severe plaque psoriasis who were eligible for systemic therapy or phototherapy.8-12

The VOYAGE 1 and VOYAGE 2 studies included 1443 patients combined. Guselkumab treatment demonstrated significant improvement at week 16 versus placebo (P <.001).9-11

The NAVIGATE study included 268 patients who did not have an adequate response by week 16 with ustekinumab (Stelara), an IL-12/IL-23 antagonist.9,12 Patients with an inadequate response to ustekinumab were then randomized to guselkumab 100 mg or to continued treatment with ustekinumab.9 Among patients who did not respond to ustekinumab at week 16, by week 28, 31% of those who received guselkumab achieved an Investigator’s Global Assessment (IGA) score of 0 or 1, with a ≥2 grade improvement, versus 14% of patients who received ustekinumab.9,12

The phase 3 ORION study evaluated the efficacy, safety, and pharmacokinetics of guselkumab one-press injector in 78 patients who were randomized to guselkumab or to placebo. Significantly more patients who received treatment with guselkumab one-press achieved an IGA score of 0 or 1 (81%) or a Psoriasis Area and Severity Index (PASI) 90 response (75%) at week 16 compared with those who received placebo (0% for both end points; Table).9,13

Table

In addition, a greater proportion of patients who received guselkumab one-press achieved an IGA score of 0 versus those who received placebo (56% vs 0%, respectively; P <.001) and a PASI 100 response versus placebo (50% vs 0%, respectively) at week 16.9,13

Adverse Reactions

The most common adverse reactions associated with guselkumab include 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%).9

Serious adverse reactions were reported in 1.9% of patients in the guselkumab group compared with 1.4% of patients in the placebo group. Elevated liver enzymes were more common among patients receiving guselku­mab (2.6%) than those receiving placebo (1.9%).9

As is the case with other therapeutic proteins, guselkumab has the potential for immunogenicity. Up to week 52, approximately 6% of patients who received guselkumab had antidrug antibodies.9

Contraindications

Guselkumab is contraindicated in patients with serious hypersensitivity reactions to guselkumab or to any of its excipients.9

Drug Interactions

The use of live vaccines should be avoided in patients who receive treatment with guselkumab.9

Patients initiating treatment with guselkumab who are receiving concomitant treatment with cytochrome P450 substrates—particularly substrates with a narrow therapeutic index—may need to be monitored for therapeutic effect or for drug concentration and may require dosage adjustments.9

Use in Specific Populations

Data about the use of guselkumab in pregnant wo­men are not available to determine the potential risk for the fetus.9

Data are not available on the effects of guselkumab on breastfed infants 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 or from the mother’s underlying condition.9

Of 1823 patients with plaque psoriasis who received treatment with guselkumab, 98 were aged ≥65 years, and 6 patients were aged ≥75 years; among these patients, no overall differences were reported between older and younger patients. However, the number of patients aged ≥65 years was insufficient to establish potential differences in response.9

Warnings and Precautions

Guselkumab treatment is associated with an increased risk for infection. Patients should be advised to seek medical help if they have signs of chronic or acute infection. If a serious infection develops, guselkumab should be discontinued until the infection resolves, and the patient should be monitored closely.9

Before beginning treatment with guselkumab, patients should be evaluated for tuberculosis (TB): guselkumab should not be administered to patients with active TB infections. Before initiating treatment with guselkumab, anti-TB therapy should be considered in patients with a history of active or latent TB. During and after guselkumab treatment, patients should be monitored for TB.9

Serious hypersensitivity reactions have occurred with guselkumab, including some that required hospitalization. If a serious hypersensitivity reaction occurs, guselkumab should be discontinued and appropriate therapy should be initiated.9

Before initiating guselkumab treatment, completion of age-appropriate, guideline-recommended immunizations should be considered. The use of live vaccines should be avoided in patients who receive guselkumab.9

Conclusion

The recent FDA approval of guselkumab one-press injector provides a novel, patient-controlled treatment option for appropriate patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. In the phase 3 clinical trial ORION, the majority of patients who received guselkumab treatment with the novel one-press injector in the ORION study had positive responses, resulting in an IGA of 0 or 1 (81%) and a PASI 90 response (76%) at week 16 versus no responses on both end points among those who received a placebo. This new IL-23 blocker initially received accelerated approval in 2017 and has demonstrated significant clinical benefits for patients with moderate-to-­severe psoriasis in 4 clinical trials.

References

  1. National Psoriasis Foundation. Statistics. www.psoriasis.org/content/statistics. Accessed May 20, 2019.
  2. Centers for Disease Control and Prevention. Psoriasis. www.cdc.gov/psoriasis/index.htm. Accessed May 23, 2019.
  3. American Academy of Dermatology. What is psoriasis? www.aad.org/public/diseases/scaly-skin/psoriasis/what-is-psoriasis. Accessed May 20, 2019.
  4. World Health Organization. Global report on psoriasis. Geneva, Switzerland; 2016. https://apps.who.int/iris/bitstream/handle/10665/204417/9789241565189_eng.pdf?sequence=1&isAllowed=y. Accessed May 21, 2019.
  5. American Academy of Dermatology. Psoriasis treatment: biologics. www.aad.org/public/diseases/scaly-skin/psoriasis/diagnosis-and-treatment-of-psoriasis/biologics. Accessed May 23, 2019.
  6. National Psoriasis Foundation. NPF professional fact sheets—psoriasis treatments. www.psoriasis.org/publications/patient-education/fact-sheets. Accessed May 20, 2019.
  7. Johnson & Johnson. Janssen announces U.S. FDA approval of novel Tremfya (guselkumab) one-press patient-controlled injector for adults with moderate-to­severe plaque psoriasis. February 27, 2019. www.jnj.com/janssen-announces-u-s-­fda-approval-of-novel-tremfya-guselkumab-one-press-patient-controlled-injector-for-adults-with-moderate-to-severe-plaque-psoriasis. Accessed May 17, 2019.
  8. Johnson & Johnson. Janssen announces U.S. FDA approval of Tremfya (guselkumab) for the treatment of moderate to severe plaque psoriasis. 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 May 17, 2019.
  9. Tremfya (guselkumab) injection, for subcutaneous use [prescribing information]. Horsham, PA: Janssen Biotech; April 2019.
  10. Blauvelt A, Papp KA, Griffiths CEM, 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. Erratum in: J Am Acad Dermatol. 2017;76:1226.
  11. 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. Erratum in: J Am Acad Dermatol. 2017;76:1226.
  12. 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.
  13. Ferris LK, Ott E, Jiang J, et al. Efficacy and safety of guselkumab, administered with a novel patient-controlled injector (One-Press), for moderate-to-­severe psoriasis: results from the phase 3 ORION study. J Dermatolog Treat. 2019 Mar 19. Epub ahead of print.
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