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FDA Decisions to Watch in Rheumatology in Second Half of 2022

The approval and implementation of new drugs can vastly improve quality of life and reduce signs and symptoms of disease burden in patients with rheumatic and dermatologic diseases.

FDA Decisions to Watch in Rheumatology


July 7: Pegloticase (KRYSTEXXA) plus Methotrexate

The US Food and Drug Administration (FDA) granted priority review of the supplemental Biologics License Application (sBLA) that would expand the pegloticase label to include the co-treatment of pegloticase plus methotrexate in patients with uncontrolled gout. The decision was based on results from the phase 4, randomized, placebo-controlled MIRROR trial, which showed that 71% of patients receiving pegloticase combination therapy achieved a complete response when compared with patients receiving pegloticase plus placebo. Pegloticase is a recombinant uricase enzyme that converts urate into allantoin that is more easily excreted from the body.

“I think this is going to show much better promise for patients in the long run,” Jeff Peterson, MD, President of Washington Rheumatology Alliance, Director at Northwest Rheumatism Society, Western Washington Medical Group Arthritis Clinic's clinical research department, hypothesized. “Prior to using immunomodulation with pegloticase, we were getting about a 40% success rate of getting patients all the way through the treatment protocols. Fifty-eight percent of the patients were failing, having infusion reactions, and exhibiting a lack of efficacy from the drug. Since we have been using immunomodulation, that number has essentially doubled.”

July 29: Roflumilast Cream for Plaque Psoriasis

If approved, roflumilast cream 0.3% (ARQ-151), a once-daily topical formulation of roflumilast, would be the first and only topical phosphodiesterase type 4 (PDE4) inhibitor for treating the symptoms of psoriasis in adults and adolescents. The FDA acceptance for review of the new drug application (NDA) is supported by positive efficacy data from the phase 3, randomized, parallel, double-blind, vehicle-controlled, multi-national, multicenter DERMIS 1 and DERMIS 2 trials as well as a long-term phase 2b safety study. Results from DERMIS 1 and DERMIS 2 showed roflumilast met its primary endpoint and had an Investigator Global Assessment (IGA) success rate of 42.4% and 37.5%, respectively. The cream also reduced itch (Worst Itch-Numerical Rating Scale), and improved patient perceptions of symptoms (Psoriasis Symptoms Diary) and Psoriasis Area Severity Index-75 (PASI-75). Durable efficacy of roflumilast cream was observed through 52 and 64 weeks in the long-term safety study.

“Topical treatments are the standard therapies for the majority of psoriasis patients, but they often come with compromises between efficacy, tolerability and long-term use,” Patrick Burnett, MD, PhD, FAAD, Chief Medical Officer, Arcutis, stated. “With these challenges in mind, we developed roflumilast cream as a formulation for chronic use anywhere on the body, including the face and sensitive intertriginous areas.”

September 10: Deucravacitinib

The FDA accepted the NDA, with a Prescription Drug User Fee Act (PDUFA) goal date of September 10, 2022, and the European Medicines Agency (EMA) has authorized the Marketing Authorization Application (MAA) for deucravacitinib for the treatment of adults with moderate-to-severe plaque psoriasis. The drug, a first-in-class, oral, selective tyrosine kinase 2 (TYK2) inhibitor, selectively targets and inhibits interleukin-23 (IL-23), IL-12 and Type 1 interferon (IFN).

Applications are based on positive results from the global, multicenter, randomized, double-blind, phase 3 POETYK PSO-1 and POETYK PSO-2 studies, presented at the American Academy of Dermatology Virtual Meeting Experience and the European Academy of Dermatology and Venerology 30th Anniversary Congress, which showed that deucravacitinib (6 mg daily) exhibited significant and clinically meaningful improvements in skin clearance, quality of life, and symptom burden when compared with both placebo and apremilast (30 mg twice daily). Primary endpoints were the percentage of patients who achieved PASI75 response and the static Physician’s Global Assessment (sPGA) score of 0 or 1 at week 16 when compared with placebo. Secondary endpoints were the percentage of patients who achieved PASI75 and sPGA 0/1 at week 16 compared with apremilast. The drug was well-tolerated, and few patients discontinued treatment due to adverse events.

“There is a strong need for more effective and well-tolerated oral therapies for people living with moderate to severe plaque psoriasis, as many remain undertreated or even untreated,” Jonathan Sadeh, MD, MSc, senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb, stated. “Findings from the pivotal POETYK-PSO trials demonstrate the potential of deucravacitinib to elevate the oral standard of care for individuals who are candidates for systemic therapy. We look forward to continuing to work with the FDA and EMA with the goal of bringing deucravacitinib to patients and physicians as quickly as possible.”

September 30: Dupilumab for Prurigo Nodularis

The FDA has granted priority review of the sBLA for dupilumab, a fully human monoclonal antibody that inhibits IL-4 and IL-13 pathways, key drivers of type 2 inflammation, for the treatment of adults with prurigo nodularis based on 2 phase 3 trials, PRIME and PRIME2, that evaluated the safety and efficacy of the drug. The trials met primary and secondary endpoints and showed significant improvement in disease signs and symptoms when compared with placebo, including a reduction in itch and skin lesions. The safety profile was consistent with previously known profile of dupilumab in the treatment of atopic dermatitis, with conjunctivitis reported as the most common adverse event.

Prurigo nodularis, which affects approximately 75,000 patients in the US, is an inflammatory skin condition that causes intense and persistent itch along with thick skin lesions (nodules). Patients also commonly report painful burning, stinging, and tingling of the skin. Uncontrolled prurigo nodularis can negatively impact a patient’s mental health, quality of life, and social interactions. As the safety risks of long-term, high-potency topical steroids are well known, alternate treatment options, such as dupilumab, are critically important.