Amgen's Otezla Demonstrates Strong Phase 3 Efficacy in Mild-to-Moderate Plaque Psoriasis, Significantly Improving Disease Severity

April 26, 2021 News /BioValleyBIOON/ -- Amgen recently at the 2021 American Academy of Dermatology virtualConferenceAnnounced the oral anti-inflammatory drug Otezla (apremilast) at the Experience (AAD VMX)Treatment of Mild to Moderate Plaque Psoriasispositive results from the placebo-controlled Phase 3 ADVANCE trial. The data show that,Compared with placebo, Otezla significantly improved disease severity regardless of the body surface area (BSA) affected by the disease.

In February 2021, based on data from the ADVANCE study, Amgen submitted to the U.S.FDAA supplemental New Drug Application (sNDA) was submitted to expand the indication of Otezla for the treatment of adult patients with mild-to-moderate plaque psoriasis who are candidates for phototherapy or systemic therapy.

Otezla is an oral anti-inflammatory drug from Celgene, which was acquired by Amgen for $13.4 billion in August 2019. In January 2019,Bristol-Myers Squibb (BMS) Acquires Celgene for $74 Billion, and as the U.S. Federal Trade Commission (FTC)Antitrust Reviewa part of,Otezla was forced to be sold and subsequently acquired by Amgen。

Otezla is an oral, selective small-molecule inhibitor of phosphodiesterase 4 (PDE4) approved for three indications: moderate-to-severe plaque psoriasis, active psoriatic arthritis, and oral ulcers associated with Behçet’s disease. At the time of acquisition, Otezla was the only oral, non-biologic therapy for psoriasis and psoriatic arthritis, and the only medication indicated for oral ulcers associated with Behçet’s disease. According to Amgen’s 2020 performance report, Otezla generated $2.195 billion in sales, making it Amgen’s third best-selling drug.

“Many patients with mild-to-moderate plaque psoriasis continue to report challenges in controlling disease symptoms, despite the availability of current topical treatments, which can significantly impact their daily lives,” said Linda Stein Gold, M.D., principal investigator of the ADVANCE study and Director of Dermatologic Clinical Research at Henry Ford Health System in Detroit. “The results of the ADVANCE study demonstrate that oral Otezla significantly improved clinical measures of disease severity, such as body surface area and scalp involvement.”

David M. Reese, M.D., Executive Vice President of Research and Development at Amgen, stated, “The positive results from the ADVANCE study add to the growing body of evidence supporting the potential benefits of Otezla for patients with mild-to-moderate plaque psoriasis. We look forward to continuing to work withFDAcollaboration to expand the use of oral Otezla to adult patients with mild-to-moderate disease.”

Mild-to-Moderate Plaque Psoriasis (Image Source: dermatologyadvisor.com)

ADVANCE (PSOR-022, NCT03721172) was a multicenter, randomized, placebo-controlled, double-blind Phase 3 study evaluating the efficacy and safety of Otezla in the treatment of mild-to-moderate plaque psoriasis. Mild-to-moderate plaque psoriasis was defined as body surface area (BSA) involvement of 2%–15%, a Psoriasis Area and Severity Index (PASI) score of 2–15, and a static Physician’s Global Assessment (sPGA) score of 2–3. In this study, 595 patients were randomized in a 1:1 ratio to two groups: one group received oral Otezla 30 mg twice daily (n=297), and the other group received placebo (n=298), for a treatment period of 16 weeks. Upon completion of the 16-week treatment, all patients received Otezla in an open-label extension phase through Week 32. The primary endpoint was the percentage of patients achieving an sPGA response at Week 16. An sPGA response was defined as an sPGA score of clear (0) or almost clear (1), with a reduction of at least 2 points from baseline.

The results showed that the study met its primary endpoint: at Week 16 of treatment, a significantly higher proportion of patients in the Otezla group achieved an sPGA 0/1 response compared with the placebo group (21.6% vs. 4.1%, p < 0.0001). These clinical improvements were sustained through Week 32.

Furthermore, at Week 16 of treatment, the Otezla group demonstrated statistically significant improvements across all secondary endpoints compared with the placebo group, including: a higher proportion of patients achieving BSA ≤3% among those with baseline BSA ≤5% (71.7% vs. 35.8%), ≥75% improvement in BSA (29.0% vs. 6.1%), and Scalp Physician Global Assessment (ScPGA) response rates of clear or almost clear skin (ScPGA 0/1: 35.6% vs. 12.9%).

Consistent improvements in disease severity were also observed in adult patients with BSA > 5%. At Week 16 of treatment, a higher proportion of patients with BSA > 5% in the Otezla group achieved BSA ≤ 3% (54.6% vs. 14.9%), at least 75% improvement in BSA (36.8% vs. 8.6%), and a ScPGA response score of 0/1 (50.6% vs. 19.2%) compared to the placebo group.

In this trial, the observed adverse events were consistent with the known safety profile of Otezla. In the Otezla treatment group, the most commonly reported (≥5%) treatment-emergent adverse events (TEAEs) were diarrhea (14.3%), headache (12.9%), nausea (12.7%), upper respiratory tract infection (8.5%), and nasopharyngitis (6.8%).

Psoriasis is a severe chronic inflammatory disease that causes raised, red, scaly patches to appear on the skin. It typically affects the outer aspects of the elbows, knees, or scalp, but can occur anywhere on the body. Approximately 125 million people worldwide have psoriasis, including about 14 million in Europe and more than 7.5 million in the United States. About 80% of these patients have plaque psoriasis.

Otezla (apremilast) is an oral, selective small-molecule inhibitor of phosphodiesterase 4 (PDE4) that modulates the network of pro-inflammatory and anti-inflammatory mediators intracellularly. PDE4 is a cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase and the predominant PDE isoform in inflammatory cells. Inhibition of PDE4 leads to increased intracellular cAMP levels, which is believed to indirectly regulate the production of inflammatory mediators. The precise mechanism by which Otezla exerts its therapeutic effect in patients remains unclear.

Currently, Otezla has been approved for three therapeutic indications: (1) treatment of adult patients with moderate-to-severe plaque psoriasis; (2) treatment of adult patients with active psoriatic arthritis; and (3) treatment of oral ulcers associated with Behçet’s disease in adult patients. Since its initial approval by the U.S.FDASince its approval for marketing, more than 250,000 patients in the United States with moderate-to-severe plaque psoriasis or active psoriatic arthritis have received treatment with Otezla. (Bioon.com)

Original Source: OTEZLA (apremilast) Significantly Improved Measures Of Disease Severity In Adults With Mild-To-Moderate Plaque Psoriasis