|ME Newswire / Business Wire|
SUMMIT, N.J - Monday, March 24th 2014
OTEZLA demonstrated stable improvements in PASI response up to week 52 in ESTEEM 1 OTEZLA significantly improved signs and symptoms of psoriasis, including scalp and nails, compared with placebo in ESTEEM 2 at week 16, consistent with previously-reported ESTEEM 1 data Long term safety and tolerability profile in ESTEEM 1 was consistent with previously-reported long-term data from OTEZLA clinical trial programs No clinically meaningful changes in laboratory measurements compared with placebo observed in ESTEEM 1 or 2
Celgene Corporation (NASDAQ:CELG) today released new research findings on OTEZLA® (apremilast), the Company’s oral, selective inhibitor of phosphodiesterase 4 (PDE4), from the ESTEEM 1 and 2 phase III studies in patients with moderate to severe plaque psoriasis at the 72nd Annual Meeting of the American Academy of Dermatology (AAD) Annual Meeting in Denver, CO.
In ESTEEM 1 and 2 patients received OTEZLA 30 mg twice daily (BID) or placebo for the first 16 weeks, followed by a maintenance phase through week 32 in which patients on placebo for 16 weeks were switched to OTEZLA. Patients initially randomized to OTEZLA 30 mg BID and who were PASI 75 (psoriasis area and severity index) responders at week 32 were re-randomized to either OTEZLA 30 mg BID or placebo.
ESTEEM 1 demonstrated a stable mean PASI improvement of 81 to 88 percent between weeks 32 and 52 for those patients who were treated for 52 weeks with OTEZLA 30 mg BID and who achieved a PASI-75 score at week 32 (n=77). These data are consistent with the mean PASI-75 improvement observed between weeks 16 and 32.
In the same group of patients, OTEZLA 30 mg BID continued to demonstrate improvements in difficult-to-treat areas affected by plaque psoriasis. Among patients who had nail psoriasis at baseline (n=46), the majority showed meaningful improvement in their nails. A mean percent decrease from baseline in the Nail Psoriasis Severity Index (NAPSI) of 60.2 percent was observed at week 52. Of those patients who had scalp psoriasis defined as moderate or greater at baseline (n=49), the majority continued to demonstrate meaningful improvement in their scalp psoriasis with 72.9 percent having reduction of their scalp symptoms to clear or almost clear (ScPGA 0 or 1) at week 52.
In ESTEEM 2, a significantly higher percentage of patients receiving OTEZLA 30 mg BID achieved a PASI-75 response at week 16 (primary endpoint) compared with patients who received placebo (28.8 percent vs. 5.8 percent; p<0.0001). Statistical significance at week 16 was also demonstrated for the major secondary endpoint, static Physician Global Assessment (sPGA) score of clear or almost clear (p<0.0001).
The beneficial effects of OTEZLA on psoriasis in difficult-to-treat areas of scalp, nails, palms and soles were also demonstrated in ESTEEM 2. After 16 weeks of treatment, OTEZLA 30 mg BID demonstrated significantly higher response rates versus placebo for psoriasis affecting the scalp (ScPGA 0-1: 40.9 percent vs. 17.2 percent; p<0.0001), nails (NAPSI-50: 44.6 percent vs. 18.7 percent; p<0.0001), and palm and soles (Palmoplantar Physician Global Assessment (PPPGA) 0-1: 65.4 percent vs. 31.3 percent; nominal p=0.0315).
"Psoriasis of the nails, scalp and palmoplantar regions is very difficult to treat and can be debilitating for individuals dealing with this chronic disease," said Jennifer Cather, MD, Modern Research Associates, Dallas, Texas. "Results from the 52-week analysis of the ESTEEM program suggest that early responses seen with OTEZLA treatment in multiple efficacy endpoints of plaque psoriasis, including difficult to treat areas, are durable over time. Together with the observed long-term consistent safety and tolerability profile, these findings are encouraging.”
A separate analysis of long-term (52-week) safety and tolerability data from ESTEEM 1 identified no new or unexpected adverse events (AEs) for patients treated with OTEZLA compared with results at week 16. The most frequently reported AEs during the placebo-controlled period and the long-term 52-week OTEZLA-exposure period were diarrhea, upper-respiratory tract infection, nausea, nasopharyngitis, tension headache, and headache. Discontinuation rates for diarrhea and nausea were each less than 2 percent in the OTEZLA 30 mg BID group through week 52. No serious AEs of diarrhea and nausea were reported in all groups through 52 weeks. Serious AEs were similar between placebo and OTEZLA in the first 16 weeks, and the rate did not change through the 52-week OTEZLA-exposure period. No clinically meaningful changes in laboratory measurements were identified over the OTEZLA 52-week exposure period.
No new or unexpected AEs were identified for patients treated with OTEZLA in ESTEEM 2.
In a pooled analysis of ESTEEM 1 and 2, exposure-adjusted incidence rates (per 100 patient-years) for major adverse cardiac events, serious infections including systemic opportunistic infection, or malignancies were comparable between placebo and OTEZLA treatment groups.
OTEZLA is not indicated for the treatment of patients with psoriasis in any country.
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 New Drug Submission (NDS) based on the combined data from the PALACE 1, 2 and 3 trials for psoriatic arthritis was submitted to health authorities in Canada in the second quarter of 2013. A New Drug Application (NDA) for psoriasis in the U.S., a NDS for psoriasis in Canada as well as a combined psoriatic arthritis/psoriasis Marketing Authorization Application (MAA) in Europe were all submitted to health authorities in the fourth quarter of 2013.
About ESTEEM 1 and 2
ESTEEM 1 and 2 are two large pivotal phase III randomized, placebo-controlled studies evaluating OTEZLA in patients with a diagnosis of moderate to severe plaque psoriasis for at least 12 months prior to screening, and who were also candidates for phototherapy and/or systemic therapy. Approximately 1,250 patients were randomized 2:1 to receive either OTEZLA 30 mg twice daily or placebo after an initial five-day titration period, for the first 16 weeks, followed by a maintenance phase from weeks 16-32 in which placebo patients were switched to OTEZLA 30 mg twice daily through week 32, and a randomized withdrawal phase for responders from week 32 to week 52 based on their initial OTEZLA randomization and PASI-75 response.
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.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR ADULTS WITH PSORIATIC ARTHRITIS
OTEZLA® (apremilast) is indicated for the treatment of adult patients with active psoriatic arthritis.
IMPORTANT SAFETY INFORMATION
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 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.
Psoriasis is an immune-mediated, non-contagious chronic inflammatory skin disorder of unknown cause. The disorder is a chronic recurring condition which varies in severity from minor localized patches to complete body coverage. Plaque psoriasis is the most common type of psoriasis. About 80 percent of people who develop psoriasis have plaque psoriasis, which appears as patches of raised, reddish skin covered by silvery-white scales. These patches, or plaques, frequently form on the elbows, knees, lower back, and scalp. Psoriasis occurs nearly equally in males and females. Psoriasis is believed to be most common in Caucasians and slightly less common in other ethnic groups. Worldwide, psoriasis is most common in Scandinavia and other parts of northern Europe. An estimated 125 million people worldwide have psoriasis. To learn more about the role of PDE4 in inflammatory diseases, go to www.discoverpde4.com.
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.
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.
Patrick E. Flanigan III, 908-673-9969
Vice President, Investor Relations
Catherine Cantone, 732-564-3592
Director, Corporate Communications