AMGEN PRESENTS NEW RESEARCH ON OTEZLA® (APREMILAST) IN PSORIATIC ARTHRITIS AT EULAR 2023

MOSAIC Study is First to use MRI to Assess Inflammation in Peripheral Joints and Entheses in Psoriatic Arthritis Patients

Exploratory Analysis Examines Effects of Otezla on Cardiometabolic Parameters

THOUSAND OAKS, Calif., May 30, 2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced new research examining the use of Otezla^® (apremilast) in psoriatic arthritis, including the Phase 4 MOSAIC study and an exploratory analysis of cardiometabolic risk factors, which are commonly elevated in patients with psoriatic disease. The findings will be presented at the 2023 European Congress of Rheumatology (EULAR), taking place May 31-June 3 in Milan, Italy.

"Research presented at EULAR sheds new light on psoriatic arthritis and the role of our oral medication Otezla," said Ponda Motsepe-Ditshego, vice president, Global Medical at Amgen. "Using MRI, the MOSAIC study visually captured an improvement in inflammation and no significant change in structural progression, with the effects being greater in patients with moderate as opposed to high disease activity."

MOSAIC Phase 4 Study
Unlike X-ray imaging – commonly used to assess joint damage caused by psoriatic arthritis – MOSAIC used magnetic resonance imaging (MRI), a more sensitive tool for imaging inflammation, which begins early and continues throughout the disease course in joints and entheses (sites where tendons or ligaments attach to bones). MOSAIC evaluated Otezla's effect on joint inflammation and structural progression of psoriatic arthritis measured by MRI.

"MOSAIC is the first study to use MRI to assess inflammation in peripheral joints and entheses in a clinical trial, and shows MRI offers a promising way to measure inflammatory disease activity in patients with this condition," said Professor Mikkel Østergaard, M.D., Ph.D., DMSc, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, University of Copenhagen in Copenhagen, Denmark. "The results of this study are encouraging, as they provide important insights about Otezla treatment and its efficacy on both clinical and inflammatory manifestations of psoriatic arthritis."

In MOSAIC, a multicenter, single-arm, open-label study, patients with active psoriatic arthritis who were treated with Otezla for 48 weeks had MRI of the hand (contrast-enhanced) performed at baseline, week 24 and week 48. The study evaluated change from baseline in the composite score of hand bone marrow edema (BME), synovitis and tenosynovitis in fingers 2-5, assessed by the psoriatic arthritis MRI score (PsAMRIS) at week 24 (the primary endpoint). Total inflammation score, comprised of BME, synovitis, tenosynovitis and periarticular inflammation in fingers, as well as structural progression, were also assessed.

Patients treated with Otezla had improvements in both clinical and MRI measures of inflammation up to week 48. Detailed findings include:

• Inflammation improved, reflected in the mean change from baseline in the composite inflammation score of BME, synovitis, and tenosynovitis as assessed by PsAMRIS for the full analysis set (n=98), which was -2.32 (-4.73, 0.09) at week 24 and -2.91 (-5.45, -0.37) at week 48. Significant improvements at week 24 and 48 in the per protocol population (n=94) were also observed.
• No significant structural progression was observed with Otezla. Total damage score – a measure of disease progression – including bone erosion, showed no significant change at weeks 24 and 48.
• In addition, patients with moderate disease activity as measured by Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) experienced greater reductions in inflammation with Otezla as compared to those with high disease activity.
• Common treatment-emergent adverse events were diarrhea (33.6%), nausea (12.3%), headache (10.7%), nasopharyngitis (7.4%) and dyspepsia (6.6%).

Findings will be presented Friday, June 2 at 12:10 p.m. CEST: POS0226, Poster Tour Session: Apremilast Reduces Inflammation as Measured by MRI of the Hand in Patients with Psoriatic Arthritis: Primary Results from the Phase 4 MOSAIC Study.

Otezla's Effect on Cardiometabolic Parameters in Psoriatic Arthritis
A second EULAR presentation includes data evaluating the effects of Otezla on cardiometabolic parameters (low- and high-density lipoprotein [LDL, HDL], body mass index [BMI] and HbA1c levels) in 781 patients with psoriatic arthritis at 52 weeks. The post-hoc exploratory analysis of data from five pooled Phase 3 trials (PALACE 1-4, ACTIVE) showed Otezla treatment was associated with improvement in cardiometabolic parameters across psoriatic disease activity groups. Among the findings reported:

• Mean LDL in the overall population at baseline decreased by 2.0 mg/dL on average at week 52; 52.3% of patients moved from the high LDL category (≥160 mg/dL) at baseline to borderline (>129 – <160 mg/dL) or normal (≤129 mg/dL) at week 52; and 38.3% changed from borderline high to normal LDL levels.
• Mean BMI was 30.3 kg/m² in the overall population at baseline and decreased by 0.5 kg/m² at week 52; 9.0% of patients changed from the obese category (≥30 kg/m²) to the overweight category (25 – <30 kg/m²) and 12.3% of patients changed from the overweight category to the normal category (<25 kg/m²).
• 50.4% of patients who had prediabetes changed to normal HbA1c levels and 40.0% moved from diabetes to prediabetes at week 52.

Findings will be presented Saturday, June 3 at 10:30 a.m. CEST: POS1527, Poster Session: Effects of Apremilast on Changes in Cardiometabolic Parameters by Diabetes and Obesity Status in Patients with Psoriatic Arthritis.

About Psoriatic Arthritis    
Psoriatic arthritis is a chronic, inflammatory form of arthritis, which can cause swelling, stiffness and pain in and around the joints that worsens over time and can decrease physical function. It is estimated that nearly 38 million people worldwide have psoriatic arthritis.¹ Around a third of people living with psoriasis may go on to develop psoriatic arthritis.¹ If left untreated, psoriatic arthritis can cause disability.

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.

Since its initial FDA approval in 2014, Otezla has been prescribed to more than 840,000 patients worldwide.²

Otezla^® (apremilast) U.S. INDICATIONS 

INDICATIONS

Otezla^® (apremilast) is indicated for the treatment of adult patients with 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^® is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation

Warnings and Precautions

• Hypersensitivity: Hypersensitivity reactions, including angioedema and anaphylaxis, have been reported during postmarketing surveillance. If signs or symptoms of serious hypersensitivity reactions occur, discontinue Otezla and institute appropriate therapy
• 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
• Plaque Psoriasis: Treatment with Otezla is associated with an increase in depression. During clinical trials in patients with moderate to severe plaque psoriasis, 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
• Behçet'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
• Plaque Psoriasis: Body weight loss of 5-10% occurred in 12% (96/784) of patients with moderate to severe plaque psoriasis 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

Adverse Reactions

• Plaque Psoriasis: The most common adverse reactions (≥ 5%) are diarrhea, nausea, upper respiratory tract infection, and headache, including tension headache. Overall, the safety profile of Otezla in patients with mild to moderate plaque psoriasis was consistent with the safety profile previously established in adult patients with moderate to severe plaque psoriasis
• Psoriatic Arthritis: The most common adverse reactions (≥ 5%) are diarrhea, nausea, and headache
• Behçet's Disease: The most common adverse reactions (≥ 10%) are diarrhea, nausea, headache, and upper respiratory tract infection.

Use in Specific Populations

• Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of fetal loss.

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.     

Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2022, Amgen was named one of the "World's Best Employers" by Forbes and one of "America's 100 Most Sustainable Companies" by Barron's.

For more information, visit Amgen.com and follow us on Twitter, LinkedIn, Instagram, TikTok and YouTube.

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., Kyowa Kirin Co., 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), the Five Prime Therapeutics, Inc. acquisition, the Teneobio, Inc. acquisition, the ChemoCentryx, Inc. acquisition, or the proposed acquisition of Horizon Therapeutics plc, 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, 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 
Michael Strapazon, 805-313-5553 (media)
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References
¹ National Psoriasis Foundation. Psoriasis Statistics. Available at: https://www.psoriasis.org/psoriasis-statistics/. Accessed May 18, 2023.
² Amgen Data on File. March 2023.

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