FDA Accepts Amgen's Supplemental New Drug Application For Otezla® (apremilast) For Adults With Mild-To-Moderate Plaque Psoriasis

THOUSAND OAKS, Calif., May 5, 2021 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental New Drug Application (sNDA) for Otezla^® (apremilast) for the treatment of adults with mild-to-moderate plaque psoriasis who are candidates for phototherapy or systemic therapy. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of December 19, 2021.

"Otezla has been prescribed to hundreds of thousands of patients with moderate-to-severe plaque psoriasis. Based on the positive Phase 3 ADVANCE data, we believe it could play an important role in addressing the unmet need for adults affected by mild-to-moderate plaque psoriasis who have had challenges managing their disease with existing topical therapies alone," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "The FDA's acceptance of this sNDA for Otezla is a significant milestone toward achieving our goal of potentially providing the first and only oral treatment option for the underserved mild-to-moderate patient population."

The sNDA, submitted on February 19, 2021, is based on data from the Phase 3 ADVANCE trial, a multicenter, randomized, placebo-controlled, double-blind study to assess the efficacy of Otezla^® (apremilast) in adults with mild-to-moderate plaque psoriasis, which demonstrated that oral Otezla 30 mg twice daily achieved a statistically significant improvement in the primary endpoint of the static Physician's Global Assessment (sPGA) response at week 16 compared to placebo. Otezla also demonstrated statistically significant improvements in key secondary endpoints compared to placebo, including achieving at least a 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 at week 16. These clinical improvements were maintained through week 32.

The safety profile of Otezla in the ADVANCE trial was consistent with previously reported data from Otezla clinical trial programs. 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 were recently presented at the American Academy of Dermatology Virtual Meeting Experience 2021.

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 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

About ADVANCE (PSOR-022)
ADVANCE (NCT03721172) 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%, Psoriasis Area and Severity Index (PASI) score of 2 to 15, sPGA score of 2 to 3). The study randomized 595 patients 1:1 to receive Otezla (n=297) 30 mg twice daily or placebo (n=298) 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.

About Psoriasis
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.² Approximately 125 million people worldwide have psoriasis, including around 14 million people in Europe and more than 8 million people in the United States.^3,4 About 80% of those patients have plaque psoriasis.⁵

About Otezla^® (apremilast)
OTEZLA^® (apremilast) 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 phase 3 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: During clinical trials, 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: During clinical trials, 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: During the phase 3 clinical trial, 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

Adverse Reactions

• Psoriasis: Adverse reactions reported in ?5% of patients were (Otezla%, placebo%): diarrhea (17, 6), nausea (17, 7), upper respiratory tract infection (9, 6), tension headache (8, 4), and headache (6, 4)
• Psoriatic Arthritis: Adverse reactions reported in at least 2% of patients taking Otezla, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 16 weeks (after the initial 5-day titration), were (Otezla%, placebo%): diarrhea (7.7, 1.6); nausea (8.9, 3.1); headache (5.9, 2.2); upper respiratory tract infection (3.9, 1.8); vomiting (3.2, 0.4); nasopharyngitis (2.6, 1.6); upper abdominal pain (2.0, 0.2)
• Behçet's Disease: Adverse reactions reported in at least ?5% of patients taking Otezla, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 12 weeks, were (Otezla%, placebo%): diarrhea (41.3, 20.4); nausea (19.2, 10.7); headache (14.4, 10.7); upper respiratory tract infection (11.5, 4.9); upper abdominal pain (8.7, 1.9); vomiting (8.7, 1.9); back pain (7.7, 5.8); viral upper respiratory tract infection (6.7, 4.9); arthralgia (5.8, 2.9)

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

Please click here for Otezla^® Full Prescribing Information.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

Forward-Looking Statements

This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or any collaboration to manufacture therapeutic antibodies against COVID-19), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), or the Five Prime Therapeutics, Inc. acquisition, as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems such as the ongoing COVID-19 pandemic on our business, outcomes, progress, or effects relating to studies of Otezla as a potential treatment for COVID-19, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

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CONTACT: Amgen, Thousand Oaks 
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¹ Data on File at Amgen Inc.
² National Psoriasis Foundation. About Psoriasis. Available at: https://www.psoriasis.org/about-psoriasis. Accessed September 22, 2020.
³ National Psoriasis Foundation. Statistics. Available at: https://www.psoriasis.org/content/statistics. Accessed October 8, 2020.
⁴ Ortonne JP, Prinz JC. Alefacept: a novel and selective biologic agent for the treatment of chronic plaque psoriasis. Eur J Dermatol. 2004;14(1):41?45.
⁵ National Psoriasis Foundation. Plaque Psoriasis. Available at: https://www.psoriasis.org/about-psoriasis/types/plaque. Accessed September 22, 2020.

SOURCE Amgen