Top-Line Results Positive for New Plaque Psoriasis Treatment

David M. Reese, MD

Amgen announced the positive top-line results testing apremilast (Otezla) in plaque psoriasis patients.

In the phase 3, multicenter, randomized, placebo-controlled, double-blind trial dubbed ADVANCE, investigators tested apremilast in 595 adults with mild-to-moderate plaque psoriasis.

During the first 16 weeks of the trial, patients received either placebo or 30 mg of apremilast twice daily. All patients then received the treatment during an open-label extension phase through week 32.

The investigators found that 30 mg of treatment twice daily could achieve statistically significant improvement when compared to placebo.

Overall, patients met the primary endpoint of the static Physician's Global Assessment (sPGA) response (defined as an sPGA score of clear (0) or almost clear (1) with at least a 2-point reduction from baseline) at week 16.

Patients often achieved the week 16 secondary endpoints of at least a 75% improvement from baseline in the percent of affected body surface area (BSA), the change in BSA total score from baseline, and the change in Psoriasis Area and Severity Index (PASI) total score from baseline.

Each of these secondary endpoints were statistically significant for the treatment effect of apremilast compared to placebo.

There were some adverse events observed in the trial, which were consistent with the known safety profile of apremilast and occurred in at least 5% of patients in either treatment arm of the study.

The common reported adverse events included diarrhea, headache, nausea, nasopharyngitis, and upper respiratory tract infections.

“Many patients with mild-to-moderate plaque psoriasis who use topical therapies still have challenges managing their psoriasis," David M. Reese, MD, executive vice president of Research and Development at Amgen, said in a statement. "We look forward to discussions with the FDA about the potential to bring Otezla, which has already been prescribed to hundreds of thousands of patients with moderate-to-severe psoriasis, to more patients who may need additional therapeutic options."

Apremilast currently has approval from the US Food and Drug Administration (FDA) for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for phototherapy or systemic therapy, as well as for adult patients with active psoriatic arthritis and adult patients with oral ulcers associated with Bechet’s Disease.

Since it was initially approved in 2014, the treatment has been prescribed to more than 250,000 patients with moderate-to-severe plaque psoriasis or active psoriatic arthritis in the US.

There are approximately 125 million people worldwide suffering from psoriasis, including around 14 million people in Europe and more than 7.5 million people in the US. About 80% of these patients have plaque psoriasis.

Apremilast is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition causes increased intracellular cAMP levels, which is believed to indirectly modulate the production of inflammatory mediators.

However, the specific mechanisms the apremilast exerts its therapeutic action in patients is not yet well-defined.