Amgen Submits sNDA to Expand Otezla (apremilast) Indication to Mild-to-Moderate Plaque Psoriasis in Adults

Compiled by Fan Dongdong

Recently, Amgen announced the submission of a supplemental New Drug Application (sNDA) for its oral medication Otezla (apremilast). The company seeks to expand the indications for Otezla to include the treatment of adult patients with mild-to-moderate plaque psoriasis who are candidates for phototherapy or systemic therapy.

As early as 2014, Otezla received FDA approval for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for phototherapy and systemic therapy. This time, the supplemental New Drug Application (sNDA) submitted by Amgen to the U.S. FDA is primarily based on data from the Phase III ADVANCE trial.

The ADVANCE (PSOR-022) trial was a Phase 3, multicenter, randomized, placebo-controlled, double-blind study primarily evaluating the efficacy and safety of Otezla in patients with mild-to-moderate plaque psoriasis (body surface area [BSA] involvement of 2% to 15%, Psoriasis Area and Severity Index [PASI] score of 2 to 15, and static Physician’s Global Assessment [sPGA] score of 2 to 3). A total of 595 patients were randomized in a 1:1 ratio to receive either Otezla 30 mg twice daily (n=297) or placebo (n=298) during the initial 16 weeks. Subsequently, all patients received open-label Otezla treatment through Week 32 during the open-label extension period.

The trial results demonstrated that, compared with placebo, twice-daily administration of 30 mg Otezla achieved a statistically significant improvement in the static Physician’s Global Assessment (sPGA) skin clearance score at Week 16, thereby meeting the primary endpoint. Furthermore, Otezla also achieved statistically significant improvements in key secondary endpoints. Compared with placebo, patients in the Otezla group showed at least a 75% improvement from baseline in body surface area (BSA) affected at Week 16, along with improvements in total BSA scores and Psoriasis Area and Severity Index (PASI) scores relative to baseline. In the ADVANCE trial, the observed adverse events were consistent with the known safety profile of Otezla.

Otezla is an oral, selective phosphodiesterase 4 (PDE4) inhibitor. It is the first and only PDE4 inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of plaque psoriasis. PDE4 is a cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase. Inhibition of PDE4 leads to increased intracellular cAMP levels in patients’ cells, which is believed to indirectly modulate the production of inflammatory mediators, thereby producing therapeutic effects. Psoriasis is a severe chronic inflammatory disease that causes raised, red, scaly plaques on the skin, commonly affecting the elbows, knees, or scalp. There are approximately 125 million psoriasis patients worldwide, including about 14 million in Europe and 7.5 million in the United States, with 80% of these patients having plaque psoriasis.

Otezla was initially developed as a blockbuster drug by Celgene. In 2019, Amgen announced a collaboration agreement with Celgene to acquire the global rights to Otezla, a new medication for psoriasis, for $13.4 billion in cash. According to Amgen’s latest financial report for 2020, Otezla generated nearly $2.2 billion in sales revenue for the company that year. Currently, Otezla is the only approved oral, non-biologic innovative therapy for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Market analysts predict that Otezla’s sales revenue will continue to grow, potentially exceeding $3 billion by 2023.

Otezla is currently approved in the United States for three indications: the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for phototherapy or systemic therapy, adult patients with active psoriatic arthritis, and adult patients with oral ulcers associated with Behçet’s disease. Additionally, Otezla has been approved in more than 50 countries outside the United States, including those in the European Union and Japan. The greatest advantages of Otezla are its convenience and safety profile; however, this position may be challenged by Bristol Myers Squibb’s deucravacitinib.

Last November, in the Phase 3 POETYK PSO-1 pivotal clinical trial involving patients with moderate-to-severe plaque psoriasis, Bristol Myers Squibb’s TYK2 inhibitor deucravacitinib demonstrated superior efficacy compared to Otezla. The study results confirmed that, compared with placebo, a greater proportion of patients treated with once-daily 6 mg deucravacitinib for 16 weeks achieved at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) and attained static Physician’s Global Assessment (sPGA) scores of 0 or 1, indicating clear or almost clear skin. Evaluation of secondary endpoints showed that at Week 16, the proportions of patients achieving PASI 75 and sPGA 0/1 with deucravacitinib were superior to those observed with Otezla. In this study, the overall safety profile of deucravacitinib was consistent with previously reported Phase II study results.

Reference Sources:

1.Amgen Submits SNDA For Otezla For Adults With Mild-To-Moderate Plaque Psoriasis

2.Amgen Submits Supplemental New Drug Application for Otezla® (apremilast) for Adults with Mild-To-Moderate Plaque Psoriasis