SUMMIT, N.J. - Monday, November 14th 2016 [ME NewsWire]
ACTIVE trial in biologic-naïve patients met its primary endpoint, demonstrating significant improvement in ACR20 response rate at week 16 with OTEZLA versus placebo
Improvements in ACR20 and other measures of disease seen as early as week 2
ACR20 response rate increased from 38 percent at week 16 to 67 percent at week 52 for patients who received OTEZLA therapy from baseline
(BUSINESS WIRE)-- Celgene Corporation (NASDAQ: CELG) today announced findings from the ACTIVE phase 3b clinical trial of OTEZLA® (apremilast), the Company's oral, selective inhibitor of phosphodiesterase 4 (PDE4), at the 2016 American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting in Washington, D.C. The trial met its primary endpoint of significant improvement in the proportion of patients achieving an ACR20 response at week 16 with OTEZLA versus placebo in patients with active psoriatic arthritis who have not previously been treated with a biologic therapy.
The ACTIVE trial randomized 219 patients who may have had one prior conventional therapy and were not previously treated with a biologic to either OTEZLA 30 mg twice daily (n=110) or placebo (n=109). An objective of the study was to determine the clinical effects of OTEZLA compared with placebo, by examining efficacy outcomes at earlier time points than in previous studies.
“These findings show a separation from placebo as early as two weeks with oral OTEZLA in patients with psoriatic arthritis who have not been previously treated with biologics,” said Dr. Jacob Aelion, director of the West Tennessee Research Institute and clinical professor of Medicine/Rheumatology at the University of Tennessee in Memphis. “Early responses at week 2 across several measures of disease activity, including morning stiffness and enthesitis, were also seen at week 16.”
A separation between OTEZLA and placebo was seen at week 2, the study’s first efficacy assessment time point, with 16.4 percent of patients in the OTEZLA arm achieving ACR20, compared with 6.4 percent in the placebo arm. Improvements versus placebo were also seen at week 2 in 28-joint count Disease Activity Score (C-reactive protein) [−0.59 vs. −0.31, respectively], health assessment questionnaire disability index (HAQ-DI) [−0.13 vs. −0.05], morning stiffness severity [42.7 percent vs. 21.1 percent], and enthesitis (inflammation at sites where tendons or ligaments insert into bone), as measured by a change in Gladman Enthesitis Index (GEI) [−1.1 vs. −0.4]. A trend to decrease in swollen joint count was also observed in patients receiving OTEZLA compared with those on placebo (−27.7 percent for OTEZLA vs. −17.5 percent for placebo).
At week 16, 38.2 percent of patients in the OTEZLA arm achieved an ACR20 response, compared with 20.2 percent in the placebo arm. Improvements were also seen at week 16 in other measures of disease, including: 28-joint count Disease Activity Score (C-reactive protein) (−1.07 with OTEZLA vs. −0.39 with placebo), swollen joint count (−46.4 percent vs. 4.2 percent, respectively), HAQ-DI (−0.21 vs. −0.06), improvement in morning stiffness severity (46.4 percent vs. 25.7 percent), and enthesitis (−1.5 vs. −0.4).
At week 24, placebo patients crossed over to active treatment with OTEZLA. Responses demonstrated in the placebo-controlled phase were maintained through week 52. For patients who were on OTEZLA from baseline, ACR20, ACR50, and ACR70 response rates at week 52 were 67.1 percent, 36.7 percent and 21.3 percent, respectively, and observed percent change in swollen joint count was −77.5 percent. Among patients who had enthesitis at baseline, GEI of 0 was 69.8 percent.
The most commonly reported adverse events during the placebo-controlled period were nasopharyngitis (8.3 percent with OTEZLA vs. 6.4 percent with placebo), nausea (8.3 percent vs. 1.8 percent, respectively), headache (7.3 percent vs. 3.7 percent), hypertension (6.4 percent vs. 6.4 percent), diarrhea (14.7 percent vs. 11.0 percent) and upper respiratory tract infection (4.6 percent vs. 10.1 percent). Serious adverse events in the OTEZLA and placebo arms were 2.8 percent and 4.6 percent, respectively. No increase in adverse event incidence or severity was seen through week 52.
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 which is thought to indirectly modulate the production of inflammatory mediators. The specific mechanism(s) by which OTEZLA exerts its therapeutic action in patients with psoriasis or psoriatic arthritis is not well defined.
Otezla® (apremilast) is indicated for the treatment of adult patients with active psoriatic arthritis.
Important Safety Information
Otezla® (apremilast) 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 and 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, and of continued treatment with OTEZLA for patients with these symptoms. 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.
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 is decreased when OTEZLA is co-administered with strong CYP450 inducers, such as rifampin, which may result in loss of efficacy of OTEZLA. Concomitant use of OTEZLA with CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended.
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.
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.
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. Celgene undertakes 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 Celgene’s 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 Celgene’s Annual Report on Form 10-K and our other reports filed with the U.S. Securities and Exchange Commission.
Patrick E. Flanigan III, 908-673-9969
Corporate Vice President, Investor Relations
Catherine Cantone, 908-897-4256
Senior Director, Corporate Communications