Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ:CELG), today announced results from a long-term (52-week) phase III trial of OTEZLA, the Company’s oral, selective inhibitor of phosphodiesterase 4 (PDE4), in psoriatic arthritis patients who have not had prior treatment with systemic or biologic disease-modifying antirheumatic drugs (DMARDs). The data were presented at the European League Against Rheumatism Annual Congress (EULAR 2014) in Paris, France. “Physicians need a variety of options to treat psoriatic arthritis, as treatment is highly individualized and some patients may not be appropriate candidates for biologics or certain systemic therapies,” said Alvin Wells, M.D., Ph.D., director, Rheumatology and Immunology Center, Franklin, MN. “These efficacy and safety results suggest that OTEZLA monotherapy has the potential to be used for adults with active psoriatic arthritis in the first-line setting, prior to the initiation of DMARD therapy, and possibly as a long-term treatment option.” PALACE 4: 52-week Enthesitis and Dactylitis Results demonstrated that treatment with OTEZLA monotherapy in patients with pre-existing enthesitis (inflammation at sites where tendons or ligaments insert into bone) or dactylitis (a count of fingers and toes with inflammation), two key manifestations of psoriatic arthritis, resulted in long-term improvements. Results were sustained over 52 weeks in patients initially randomized to OTEZLA monotherapy and completing 52 weeks of the study. At week 52, median Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) decreased by 75.0 percent and 45.9 percent of patients receiving OTEZLA 30 mg BID achieved a score of 0, indicating no pain at any of the enthesitis sites assessed. OTEZLA 30 mg BID also resulted in a median 100 percent decrease in dactylitis count. A dactylitis count of 0, indicating no signs of dactylitis, was achieved in 68.8 percent of patients. PALACE 4: 52-week Physical Function The results of a physical function analysis from PALACE 4 demonstrated that 52 weeks of treatment with OTEZLA monotherapy resulted in sustained improvements for up to 52 weeks, as measured by validated assessment tools.
In patients who were treated with OTEZLA monotherapy continuously through 52 weeks, clinically meaningful improvements were seen at week 16 in the Health Assessment Questionnaire-Disability Index (HAQ-DI), a key instrument measuring physical function, and improvements were sustained for up to 52 weeks. HAQ-DI measures the difficulty patients have performing activities of daily life such as difficulty dressing, walking and eating.The HAQ-DI results were further supported by improvements in the short form health survey version 2 Physical Functioning (SF-36 v2 PF) seen in patients who were treated with OTEZLA monotherapy continuously through 52 weeks. PALACE 4: 52-week Safety and Tolerability Long-term (52 week) safety results from PALACE 4 identified no new safety findings for OTEZLA compared with the previously reported 24-week safety results. Safety results were consistent with previously reported results from the phase III PALACE 1, 2 and 3 clinical trials. The majority of adverse events (AEs) were mild or moderate in severity and led to a low rate of discontinuation (5.2 percent in all patients exposed to OTEZLA). The most commonly reported AEs were nausea, diarrhea, headache and upper respiratory tract infection. Nausea and diarrhea were predominantly mild in severity, occurred most frequently in the first two weeks of treatment, and often resolved within a month despite continued treatment and no medical intervention. Serious AEs occurred at low rates, were comparable across treatment groups (0.6 percent OTEZLA 30 mg BID vs. 2.8 percent placebo) and did not increase with long-term OTEZLA exposure. The mean weight loss at the end of the 52 week OTEZLA-exposure period was 1.19 kg in OTEZLA 30 mg BID and 0.91 kg in OTEZLA 20 mg BID. Similar to other OTEZLA data reported from PALACE 1, 2 and 3, these data do not indicate a need for laboratory monitoring. About PALACE 4 PALACE 4 is a phase III multi-center, double-blind, placebo-controlled, parallel-group studies with two active-treatment groups. More than 500 DMARD-naïve patients were randomized 1:1:1 to receive either OTEZLA 20 mg BID, 30 mg BID, or identically appearing placebo, for 24 weeks, with a subsequent active treatment phase up to 52 weeks, followed by a long-term safety phase in which all patients are treated with OTEZLA.
The primary endpoint was the modified American College of Rheumatology criteria for 20 percent improvement (ACR20) at week 16. Secondary endpoints included other measures of signs and symptoms of psoriatic arthritis, physical functioning, and patient-reported outcomes.OTEZLA was approved on March 21, 2014 by the U.S. Food and Drug Administration (FDA) for the treatment of adults with active psoriatic arthritis. A combined psoriatic arthritis/psoriasis Marketing Authorization Application (MAA) in Europe was submitted to health authorities in the fourth quarter of 2013. To learn more about OTEZLA visit www.otezla.com. About OTEZLA OTEZLA is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels. Important Safety Information INDICATION OTEZLA® (apremilast) is indicated for the treatment of adult patients with active psoriatic arthritis. 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 Depression: Treatment with OTEZLA is associated with an increase in adverse reactions of depression. During clinical trials, 1.0% (10/998) of patients treated with OTEZLA reported depression or depressed mood compared to 0.8% (4/495) treated with placebo; 0.3% (4/1441) of patients treated with OTEZLA discontinued treatment due to depression or depressed mood compared with none in placebo treated patients (0/495). Depression was reported as serious in 0.2% (3/1441) of patients exposed to OTEZLA, compared to none in placebo treated patients (0/495). Suicidal ideation and behavior were observed in 0.2% (3/1441) of patients on OTEZLA, compared to none on placebo (0/495). Two patients who received placebo committed suicide compared to none on OTEZLA. 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.
Weight Decrease: Body weight loss of 5-10% was reported in 10% of patients taking OTEZLA and in 3.3% of patients taking placebo. Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of OTEZLA.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 (eg, rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended. Adverse Reactions 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). Use in Specific Populations Pregnancy and Nursing Mothers: OTEZLA is Pregnancy Category C; it has not been studied in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether apremilast or its metabolites are present in human milk. Caution should be exercised when OTEZLA is administered to a nursing woman. 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 Full Prescribing Information. About Psoriatic Arthritis Psoriatic arthritis is a painful, chronic inflammatory disease characterized by pain, stiffness, swelling and tenderness of the joints, inflammation of specific ligaments and tendons, and decrease in physical functioning. It is estimated that nearly 38 million people worldwide have psoriatic arthritis. Psoriatic arthritis can impact day-to-day activities and has been reported to increase work disability. Common signs and symptoms of psoriatic arthritis include pain, stiffness, and swelling in joints. To learn more about psoriatic arthritis, go to www.discoverpsa.com. To learn more about the role of PDE4 in inflammatory diseases, go to www.discoverpde4.com. About Celgene Celgene International Sàrl, located in Boudry, Switzerland, is a wholly-owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit www.celgene.com. Forward-Looking Statements This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates,” “plans,” “will,” “outlook” and similar expressions. Forward-looking statements are based on management’s current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and other reports filed with the Securities and Exchange Commission.