FDA Approves OTEZLA® (apremilast) for the Treatment of Oral Ulcers Associated with Behçet’s Disease
Celgene Corporation (NASDAQ:CELG) today announced that the U.S. Food and Drug Administration (FDA) has approved OTEZLA® (apremilast) 30 mg twice daily (BID) for the treatment of adult patients with oral ulcers associated with Behçet’s Disease. OTEZLA, an oral, selective inhibitor of phosphodiesterase 4 (PDE4), is the first and only approved treatment option for oral ulcers associated with Behçet’s Disease, a rare, chronic, multisystem inflammatory disease that is difficult to treat.
“Oral ulcers are a recurring and debilitating manifestation that affects nearly everyone living with Behçet’s Disease, and have an important negative impact on the quality of life for these patients,” said Yusuf Yazici, M.D., Clinical Associate Professor, Department of Medicine, New York University Langone Health. “In the clinical trial, OTEZLA demonstrated improvements in measures of oral ulcers at week 12. OTEZLA has the potential to be a needed treatment option for U.S. patients and their physicians, who previously had limited options available.”
Behçet’s Disease, also known as Behçet’s Syndrome, affects approximately 5 in 100,000 people in the U.S.1,2 Oral ulcers, the most common manifestation of Behçet’s Disease occurring in more than 98% of patients, can be painful, disabling and negatively affect quality of life.3
“We are excited to provide the first and only FDA-approved treatment for oral ulcers associated with Behçet’s Disease,” said Terrie Curran, President, Celgene Inflammation & Immunology. “This approval is a reflection of Celgene’s commitment to research in areas of high unmet need, including rare diseases such as Behçet’s Disease. We remain dedicated to further studying OTEZLA and its role in inflammatory conditions.”
The FDA approval was based on efficacy and safety results from the randomized, placebo-controlled, double-blind Phase 3 RELIEF™ study evaluating OTEZLA in 207 adult patients with Behçet’s Disease with active oral ulcers who were previously treated with at least one nonbiologic medication and were candidates for systemic therapy. Results showed OTEZLA 30 mg BID resulted in a 42.7 point reduction from baseline in the pain of oral ulcers as measured by the visual analog scale (VAS) at week 12, compared with an 18.7 point reduction with placebo. The proportion of patients achieving an oral ulcer complete response (oral ulcer-free) at week 12 was 52.9% in the OTEZLA arm and 22.3% in the placebo arm. The proportion of patients achieving oral ulcer complete response by week 6 and who remained oral ulcer-free for at least six additional weeks during the 12-week treatment phase was 29.8% in the OTEZLA arm and 4.9% in the placebo arm. The daily average number of oral ulcers during the 12-week treatment phase was 1.5 in the OTEZLA arm and 2.6 in the placebo arm (based on oral ulcer counts measured at baseline and at weeks 1, 2, 4, 6, 8, 10 and 12).
“Behçet’s Disease is a chronic inflammatory disease in which patients present with symptoms such as oral ulcers that can have a significant impact on daily life,” said Mirta Avila Santos, M.D., Executive Director, American Behçet’s Disease Association. “Today’s approval for OTEZLA marks an important milestone for people with Behçet’s Disease who have been eagerly waiting for treatment options for their oral ulcers.”
The most common adverse events observed occurring in ≥10% of patients in the RELIEF trial were diarrhea (41.3% with OTEZLA; 20.4% for placebo), nausea (19.2% with OTEZLA; 10.7% for placebo), headache (14.4% with OTEZLA; 10.7% for placebo) and upper respiratory tract infection (11.5% with OTEZLA; 4.9% for placebo). The safety profile was consistent with the known safety profile of OTEZLA.
OTEZLA is now approved for three indications in the U.S., including the treatment of 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.4
OTEZLA is available in the U.S. and is dispensed through a comprehensive network of specialty pharmacies. For more information about accessing OTEZLA and patient support services (including reimbursement assistance and 24/7 nurse support), doctors and patients can contact OTEZLA® SupportPlus™ at 1-844-4OTEZLA (1-844-468-3952) or visit www.OTEZLA.com for more information.
Celgene anticipates a regulatory decision for OTEZLA in oral ulcers associated with Behçet’s Disease from the Pharmaceuticals and Medical Devices Agency in Japan in the second half of 2019. The Company also submitted a Type II Variation to the Marketing Authorization Application earlier this year seeking approval in the European Union.
About the RELIEF™ Study
The RELIEF™ study is a Phase 3 randomized, placebo-controlled, double-blind study evaluating OTEZLA 30 mg BID in 207 adult patients with Behçet’s Disease with active oral ulcers who were previously treated with at least one nonbiologic medication and were candidates for systemic therapy. This 64-week study was conducted at 53 sites across 10 countries.
In the study, 207 adult patients were randomized 1:1 to receive either OTEZLA 30 mg BID (n=104) or placebo (n=103) for the 12-week placebo-controlled treatment phase. Upon completion of week 12, all patients received OTEZLA for the 52-week active treatment phase. Efficacy was assessed based on the number and pain of oral ulcers, including the daily average number of oral ulcers during the 12-week placebo-controlled treatment phase.
About Behçet’s Disease
Behçet’s Disease is associated with abnormalities of the immune system and inflammation of the blood vessels. Behçet’s Disease is characterized by recurrent oral and genital ulcers, skin lesions, uveitis, arthritis, vascular, central nervous system and gastrointestinal involvement. Oral ulcers are present in more than 98% of Behçet’s Disease patients.
Behçet’s Disease has been classified in the U.S. as a rare or “orphan” disease by the National Institutes of Health. At this time, there are limited approved therapies to treat Behçet’s Disease in the U.S. Prevalence of Behçet’s Disease is highest in the Middle East, Asia and Japan.
About OTEZLA® (apremilast)
OTEZLA® (apremilast) 30 mg tablets 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.
U.S. PRESCRIBING INFORMATION
Otezla® (apremilast) is indicated for the treatment of 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.
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
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.
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
Psoriasis: 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: 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
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 Full Prescribing Information.
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 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. 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 our other reports filed with the U.S. Securities and Exchange Commission, including factors related to the proposed transaction between Bristol-Myers Squibb and Celgene, such as, but not limited to, the risks that: management’s time and attention is diverted on transaction related issues; disruption from the transaction make it more difficult to maintain business, contractual and operational relationships; legal proceedings are instituted against Bristol-Myers Squibb, Celgene or the combined company that could delay or prevent the proposed transaction; and Bristol-Myers Squibb, Celgene or the combined company is unable to retain key personnel.
Hyperlinks are provided as a convenience and for informational purposes only. Celgene bears no responsibility for the security or content of external websites.
All trademarks are the property of their respective owners.
1 Zeidan MJ, Saadoun D, Garrido M , Klatzmann D, Six A, Cacoub P. Behçet’s disease physiopathology: a contemporary review. Autoimmun Highlights. 2016;7(1):4.
2 Leonardo NM, McNeil J. Behçet’s disease: is there geographical variation? A review far from the Silk Road. Int J Rheumatol. 2015;2015:945262.
3 Medscape EMedicine. Dermatological Aspects of Behcet Disease Clinical Presentation. https://emedicine.medscape.com/article/1122381-clinical. Accessed February 2019.
4 Symphony Health Solution PrescriberSource PatientFocus, Includes all prescriptions from April 2014 through April 2019.
For inquiries, please contact:
Executive Director, Investor Relations
Senior Director, Corporate Communications
About Business Wire
For more than 50 years, Business Wire has been the global leader in press release distribution and regulatory disclosure.
Subscribe to releases from Business Wire
Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from Business Wire
Gilead and Galapagos Complete Closing of Their Transformative Research and Development Collaboration23.8.2019 23:01:00 EEST | Press release
Gilead Sciences, Inc. (NASDAQ: GILD) and Galapagos NV (Euronext & NASDAQ: GLPG) today announced the closing of the global research and development collaboration agreement signed on July 14, 2019. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190823005335/en/ This agreement has received clearance from the U.S. Federal Trade Commission under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 and merger control approval from the Austrian Federal Competition Authority. Under the terms of the agreement, the closing of this transaction triggers an upfront license fee payment of $3.95 billion by Gilead to Galapagos. In addition, Gilead has made an equity investment in Galapagos of approximately $1.1 billion (or approximately €960 million) by subscribing for new shares at a price of €140.59 per share, including issuance premium. As a result, Gilead now owns 13,589,686 ordinary shares of Galapagos, representing approximately 2
32 Leading Global Fashion and Textile Companies Make Commitments on Climate, Biodiversity and Oceans23.8.2019 10:47:00 EEST | Press release
Ahead of the G7 meeting at Biarritz from August 24-26, French President Emmanuel Macron, accompanied by Economy and Finance Minister Bruno Le Maire, Minister of Labour Muriel Pénicaud, and Deputy Minister of Ecological and Solidary Transition Brune Poirson, has invited to the Elysée Palace representatives of the 32 fashion and textile companies who have launched the Fashion Pact by his side. In April 2019, ahead of the G7 meeting, Emmanuel Macron had given François-Henri Pinault, Chairman and Chief Executive Officer of Kering (Paris:KER), a mission to bring together the leading players in fashion and textile, with the aim of setting practical objectives for reducing the environmental impact of their industry. In a historic move, given the scale and importance of the coalition that has been created, 32 leading companies from the fashion and textile industry have given themselves a set of shared objectives in the form of a Fashion Pact. The coalition includes groups and brands in Luxury,
Ethereum (ETH) Now Available on bitFlyer Buy/Sell23.8.2019 08:00:00 EEST | Press release
Cryptocurrency exchange bitFlyer has announced it is adding Ethereum (ETH) to its Buy/Sell trading platform. From today, bitFlyer Buy/Sell users across Europe and the US can send and receive ETH while ensuring they adhere to the same robust regulatory standards as bitFlyer guarantees for Bitcoin (BTC) transactions. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190822005486/en/ Ethereum (ETH) Now Available on bitFlyer Buy/Sell (Graphic: Business Wire) Andy Bryant, Co-head and COO, bitFlyer Europe, said, “At bitFlyer, we want to offer not just the most popular coins, but the most respected ones too, which makes ETH a logical choice to expand our service offering. Not only has ETH proved itself as a useful altcoin, particularly in relation to smart contracts, it has an incredibly strong community that surrounds it. We’re committed to offering the best customer experience whilst prioritising security and regulatory standards, a
STALICLA Announces Completion of pre-IND Meeting With FDA on STP1 for Subgroup of Patients With Autism Spectrum Disorder (ASD)23.8.2019 03:00:00 EEST | Press release
STALICLA, a Swiss Biotech company, today announced the completion of its pre-IND (Investigational New Drug) meeting with the U.S. Food and Drug Administration (FDA) on the preparation for entry of STP1 into clinical trials. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190822005559/en/ STALICLA at the Food and Drug Administration (FDA) to discuss its investigational precision medicine for Autism Spectrum Disorder (Photo: STALICLA) “We are appreciative of FDA´s technical guidance and strong interest in personalized medicine approaches for patients with Autism Spectrum Disorder. STALICLA is committed to rapidly move forward with the submission of its STP1 IND. STP1 holds the potential to become the first precision medicine for a subgroup of patients with ASD, and herald a new age for this field.” - Lynn Durham, CEO and Founder of STALICLA. ASD is a common neurodevelopmental disorder, with high level of heterogeneity, that aff
San Fang Chemical Switches to Rimini Street Support for its Oracle EBS and Oracle Database Software23.8.2019 01:00:00 EEST | Press release
Rimini Street, Inc. (Nasdaq: RMNI), a global provider of enterprise software products and services, the leading third-party support provider for Oracle and SAP software products and a Salesforce partner, today announced that San Fang Chemical Co., Ltd., a global manufacturer and distributor of artificial leather products headquartered in Taiwan, has switched to Rimini Street support for its Oracle E-Business Suite application and Oracle Database software. In addition to immediately saving 50% of its annual maintenance costs that they were previously paying the vendor, the company can now maintain its core, robust Oracle system for a minimum of 15 years from the time that they switched to Rimini Street support with no forced upgrades. San Fang Chemical has also been able to liberate its IT resources and divert its substantial cost savings to invest in more forward-looking innovation projects to help pave the way for future growth and competitive advantage. This press release features mu
Gravity Unveils its Future Plans During Gamescom 201922.8.2019 18:46:00 EEST | Press release
Gravity Interactive, Inc., a subsidiary of Gravity Co., Ltd. (NASDAQ: GRVY) which is a leading global game company, participated in Gamescom which is one of the three largest game fairs in the world, held in Cologne, Germany from August 20th to 24th. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190822005507/en/ Gravity Interactive, Inc., a subsidiary of Gravity Co., Ltd. (NASDAQ: GRVY) which is a leading global game company, participated in Gamescom which is one of the three largest game fairs in the world, held in Cologne, Germany. At the fair, Gravity announced that it plans to launch ‘Ragnarok M: Eternal Love’ in the European region on September 4th 2019. ‘Ragnarok M: Eternal Love’ will be launched in Russia and Turkey, as well as Europe and it will be serviced in seven languages including English, Portuguese, Spanish, Russian, German, French, and Turkish. (Photo: Business Wire) On August 20th, Gravity held a presentati
In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.Visit our pressroom