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Home Uncategorized Amgen Announces Positive Top-Line Results From Otezla® (apremilast) Phase 3 ADVANCE Study

Amgen Announces Positive Top-Line Results From Otezla® (apremilast) Phase 3 ADVANCE Study

May 06, 2020: “Amgen announced positive top-line results from the ADVANCE trial, a Phase 3, multicenter, randomized, placebo-controlled, double-blind study to assess the efficacy of Otezla® (apremilast) in adults with mild-to-moderate plaque psoriasis.

The study showed that oral Otezla 30 mg twice daily achieved a statistically significant improvement, compared with placebo, in 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.

In addition, the week 16 secondary endpoints of achieving at least 75% improvement from baseline in the percent of affected body surface area (BSA); change in BSA total score from baseline; and change in Psoriasis Area and Severity Index (PASI) total score from baseline were each also statistically significant for the treatment effect of Otezla compared with placebo.

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“Many patients with mild-to-moderate plaque psoriasis who use topical therapies still have challenges managing their psoriasis,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen.

“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.”

The adverse events observed in this trial were consistent with the known safety profile of Otezla. The most commonly reported adverse events that occurred in at least 5% of patients in either treatment group were diarrhea, headache, nausea, nasopharyngitis and upper respiratory tract infection.

Detailed results will be submitted for presentation at an upcoming medical meeting.

In the U.S., Otezla is approved for 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 for adult patients with oral ulcers associated with Behçet’s Disease.

Since its initial FDA approval in 2014, Otezla has been prescribed to more than 250,000 patients with moderate-to-severe plaque psoriasis or active psoriatic arthritis in the U.S.[1] 

ADVANCE (PSOR-022) is a Phase 3, multicenter, randomized, placebo-controlled, double-blind study evaluating the efficacy and safety of Otezla in patients with mild-to-moderate plaque psoriasis (defined as BSA involvement of 2% to 15%, PASI score of 2 to 15, sPGA score of 2 to 3).

The study randomized 595 patients 1:1 to receive Otezla 30 mg twice daily or placebo for the first 16 weeks. All patients then received Otezla during an open-label extension phase through week 32.

The primary endpoint was the percentage of patients with sPGA response [defined as a sPGA score of clear (0) or almost clear (1) with at least a 2-point reduction from baseline] at week 16.

Psoriasis is a serious, chronic inflammatory disease that causes raised, red, scaly patches to appear on the skin, typically affecting the outside of the elbows, knees or scalp, though it can appear on any location.

 Approximately 125 million people worldwide have psoriasis, including around 14 million people in Europe and more than 7.5 million people in the United States.

 About 80% of those patients have plaque psoriasis.

Otezla® (apremilast) 30 mg tablets is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels, which is thought to indirectly modulate the production of inflammatory mediators.

The specific mechanism(s) by which Otezla exerts its therapeutic action in patients is not well defined.

Otezla® (apremilast) U.S. INDICATIONS

Otezla® (apremilast) is indicated for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

Otezla is indicated for the treatment of adult patients with active psoriatic arthritis.

Otezla is indicated for the treatment of adult patients with oral ulcers associated with Behçet’s Disease.

Otezla® (apremilast) U.S. IMPORTANT SAFETY INFORMATION

Contraindications

  • Otezla® (apremilast) is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation

Warnings and Precautions

  • Diarrhea, Nausea, and Vomiting: Cases of severe diarrhea, nausea, and vomiting were associated with the use of Otezla. Most events occurred within the first few weeks of treatment.

    In some cases patients were hospitalized. Patients 65 years of age or older and patients taking medications that can lead to volume depletion or hypotension may be at a higher risk of complications from severe diarrhea, nausea, or vomiting.

    Monitor patients who are more susceptible to complications of diarrhea or vomiting; advise patients to contact their healthcare provider. Consider Otezla dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting

  • Depression: Carefully weigh the risks and benefits of treatment with Otezla for patients with a history of depression and/or suicidal thoughts/behavior, or in patients who develop such symptoms while on Otezla.

    Patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes, and they should contact their healthcare provider if such changes occur
    • Psoriasis: Treatment with Otezla is associated with an increase in depression. During clinical trials, 1.3% (12/920) of patients reported depression compared to 0.4% (2/506) on placebo.

      Depression was reported as serious in 0.1% (1/1308) of patients exposed to Otezla, compared to none in placebo-treated patients (0/506).

      Suicidal behavior was observed in 0.1% (1/1308) of patients on Otezla, compared to 0.2% (1/506) on placebo. One patient treated with Otezla attempted suicide; one patient on placebo committed suicide

    • Psoriatic Arthritis: Treatment with Otezla is associated with an increase in depression.

      During clinical trials, 1.0% (10/998) reported depression or depressed mood compared to 0.8% (4/495) treated with placebo.

      Suicidal ideation and behavior was observed in 0.2% (3/1441) of patients on Otezla, compared to none in placebo-treated patients.

      Depression was reported as serious in 0.2% (3/1441) of patients exposed to Otezla, compared to none in placebo-treated patients (0/495).

      Two patients who received placebo committed suicide compared to none on Otezla
    • Behcet’s Disease: Treatment with Otezla is associated with an increase in depression. During the clinical trial, 1% (1/104) reported depression or depressed mood compared to 1% (1/103) treated with placebo.

      No instances of suicidal ideation or behavior were reported in patients treated with Otezla or treated with placebo

      Weight Decrease: Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla
    • Psoriasis: Body weight loss of 5-10% occurred in 12% (96/784) of patients treated with Otezla and in 5% (19/382) of patients treated with placebo.

      Body weight loss of ≥10% occurred in 2% (16/784) of patients treated with Otezla compared to 1% (3/382) of patients treated with placebo
    • Psoriatic Arthritis: Body weight loss of 5-10% was reported in 10% (49/497) of patients taking Otezla and in 3.3% (16/495) of patients taking placebo
    • Behçet’s Disease: Body weight loss of >5% was reported in 4.9% (5/103) of patients taking Otezla and in 3.9% (4/102) of patients taking placebo
  • Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rifampin, a strong CYP450 enzyme inducer; loss of Otezla efficacy may occur.

    Concomitant use of Otezla with CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended

Use in Specific Populations

  • Pregnancy: Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of fetal loss. Consider pregnancy planning and prevention for females of reproductive potential.

    There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Otezla during pregnancy. Information about the registry can be obtained by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/otezla/
  • Lactation: There are no data on the presence of apremilast or its metabolites in human milk, the effects of apremilast on the breastfed infant, or the effects of the drug on milk production.

    The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Otezla and any potential adverse effects on the breastfed child from Otezla or from the underlying maternal condition

  • Renal Impairment: Otezla dosage should be reduced in patients with severe renal impairment (creatinine clearance less than 30 mL/min) for details, see Dosage and Administration, Section 2, in the Full Prescribing Information.”

Amgen Completes Acquisition Of Otezla® (apremilast) for the treatment of moderate-to-severe plaque psoriasis, psoriatic arthritis

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