• Connect with us
    • Information
      • About Us
      • Contact Us
      • Careers
      • Partnerships
      • Advertise With Us
      • Authors
      • Browse Topics
      • Events
      • Disclaimer
      • Privacy Policy
    • Australia
      North America
      World
    Login
    Investing News NetworkYour trusted source for investing success
    • North America
      Australia
      World
    • My INN
    Videos
    Companies
    Press Releases
    Private Placements
    SUBSCRIBE
    • Reports & Guides
      • Market Outlook Reports
      • Investing Guides
    • Button
    Resource
    • Precious Metals
    • Battery Metals
    • Base Metals
    • Energy
    • Critical Metals
    Tech
    Life Science
    Biotech Market
    Biotech News
    Biotech Stocks
    • Biotech Market
    • Biotech News
    • Biotech Stocks

    Celgene Announces Long-Term Safety Data for Oral OTEZLA®

    Chelsea Pratt
    Sep. 28, 2016 01:22AM PST
    Biotech Investing

    Celgene International, a wholly owned subsidiary of Celgene Corporation, today announced that long-term safety findings from ongoing clinical trials.

    Celgene International Sàrl, a wholly owned subsidiary of Celgene Corporation (NASDAQ: CELG), today announced that long-term safety findings from ongoing clinical trials of apremilast, the Company’s oral, selective inhibitor of phosphodiesterase 4 (PDE4), were presented at the European Academy of Dermatology and Venereology (EADV) Annual Congress in Vienna, Austria.
    Analyses of pooled 156-week (3-year) safety data from the ESTEEM 1 and 2
    and PALACE 1-3 trials were presented, which included patients with
    moderate to severe plaque psoriasis (ESTEEM) and active psoriatic
    arthritis (PALACE) who were treated with apremilast 30 mg twice-daily.
    Patients with psoriatic arthritis were treated with OTEZLA®
    alone or in combination with concomitant disease-modifying
    anti-rheumatic drugs (DMARDs), including methotrexate.
    Volker Koscielny MD, Head of Medical Affairs for Celgene in Europe said:
    “Psoriasis is a complex, multi-faceted chronic condition which makes
    treatment challenging. In addition, a significant number of patients
    will go on to develop psoriatic arthritis. Physical symptoms and disease
    impact go beyond the extent of skin involvement and therefore several
    factors, including individual patient needs, should be taken into
    account when assessing appropriate treatment options. With over 100,000
    patients globally already treated with OTEZLA® since approval3,
    it is important to note the efficacy and safety profile of OTEZLA®
    in this combined analysis of psoriasis and psoriatic arthritis
    three-year data.”
    2,242 patients were included in the pooled safety analysis up to 16
    weeks (placebo n=913; APR30 n=1,329), with 1,905 patients (3,527.5
    patient years) receiving apremilast in the APR-exposure period up to 156
    weeks.1
    Across both trial programmes up to 16 weeks, the most common adverse
    events (AEs) (≥5 percent of patients) among patients on apremilast were
    diarrhoea, nausea, headache, upper respiratory tract infection, and
    nasopharyngitis. Most cases of diarrhoea/nausea were mild to moderate in
    severity, occurred during the first 2 weeks of apremilast dosing and
    generally resolved in one month.1
    Discontinuation rates of apremilast due to diarrhoea and nausea occurred
    at rates of 1.3 percent and 1.7 percent, respectively, during the 0 to
    ≤52 week apremilast exposure period and 0.0 percent for both AEs during
    the >104 to ≤156 week apremilast exposure period.4
    The exposure-adjusted incidence rates (EAIR/100 patient years) for AEs,
    serious AEs and discontinuations due to AEs did not increase with
    increasing cumulative exposure during the apremilast-exposure period (0
    to ≥156 weeks; 3,527.5 patient-years); this was confirmed by assessment
    of rates on a year-by-year exposure basis.1
    The incidences (EAIR/100 patient years) of major adverse cardiovascular
    events (MACE), malignancies, and serious infections for patients on
    apremilast were comparable to placebo up to 16 weeks and remained low
    with prolonged exposure. No serious opportunistic infections or
    clinically meaningful effects on laboratory measurements were reported. 1
    Rates for depression or suicidality did not increase with increasing
    cumulative long-term apremilast exposure. Most patients taking
    apremilast maintained body weight within 5 percent of baseline; with
    21.1 percent experienced >5 percent weight loss over the 156 week
    apremilast-exposure periods. The rate of treatment discontinuation due
    to weight loss was low.4
    In addition, a retrospective analysis of results from ESTEEM 1 and 2
    trials examined the potential of an alternative tool to measure
    psoriasis disease severity. Improvement in Psoriasis Area and Severity
    Index (PASI) score remains the most commonly used severity assessment in
    clinical development and in practice, however its limitations –
    including scoring complexity and insensitivity to changes – mean that
    there may be opportunities to improve how psoriasis patients are
    assessed.2
    The combination of the Physician’s Global Assessment (PGA) and Body
    Surface Area (BSA) – the PGAxBSA composite tool – is a simple assessment
    which was shown to measure meaningful clinical responses of psoriasis
    patients in the ESTEEM trials including minimal disease activity and is
    sensitive to change in disease severity.2

    ——-ENDS——-

    About apremilast
    Apremilast is an oral inhibitor of phosphodiesterase 4 (PDE4) specific
    for cyclic AMP (cAMP). PDE4 inhibition results in increased
    intracellular cAMP levels which is thought to indirectly modulate the
    production of inflammatory mediators.5
    About the ESTEEM programme6
    ESTEEM 1 and 2 are two large pivotal Phase III randomized,
    placebo-controlled studies evaluating apremilast 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 apremilast 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 apremilast 30 mg twice daily through week 32. The trial also
    consisted of a randomized withdrawal phase for responders from week 32
    to week 52 based on their initial apremilast randomization and Psoriasis
    Area and Severity Index (PASI) response. Approximately 30 percent of all
    patients had received prior phototherapy and 54 percent had received
    prior conventional systemic and/or biologic therapy.
    About the PALACE programme6
    PALACE 1, 2 and 3 are three pivotal Phase III multi-center,
    double-blind, placebo-controlled, parallel-group studies with two
    active-treatment groups. Across these studies, approximately 1,500
    patients were randomized 1:1:1 to receive either apremilast 20 mg twice
    daily, apremilast 30 mg twice daily or identically-appearing placebo,
    for 16 weeks. At week 16, some placebo-treated patients were randomized
    to one of the two apremilast groups, while others remained on placebo
    through week 24. After week 24, patients began a subsequent long term,
    open-label, active treatment phase. The PALACE 1, 2 and 3 studies
    included a wide spectrum of patients with active psoriatic arthritis,
    who had been previously treated with oral disease-modifying anti
    rheumatic drugs (DMARDs), and/or biologics, with some patients who had
    previously failed a tumour necrosis factor (TNF) blocker. At baseline,
    64.2 percent of patients receiving apremilast in PALACE 1, 2, and 3 were
    receiving concomitant DMARDs, including methotrexate.
    Taken together, the PALACE program is the largest psoriatic arthritis
    program to date intended for regulatory submission.
    ADDITIONAL IMPORTANT SAFETY INFORMATION based on EU label
    Therapeutic indications
    OTEZLA® is approved for the treatment of moderate-to-severe
    chronic plaque psoriasis in adult patients who failed to respond to or
    who have a contraindication to, or are intolerant to other systemic
    therapy including cyclosporine, methotrexate or psoralen and
    ultraviolet-A light (PUVA).
    OTEZLA®, alone or in combination with DMARDs, is also
    indicated for the treatment of active psoriatic arthritis in adult
    patients who have had an inadequate response or who have been intolerant
    to a prior DMARD therapy.
    Contraindications
    OTEZLA® (apremilast) is contraindicated in patients
    with known hypersensitivity to the active substance or to any of the
    excipients in the formulation.
    OTEZLA® is contraindicated during pregnancy.
    Warnings and precautions
    Patients with rare hereditary problems of galactose intolerance, lapp
    lactase deficiency or glucose-galactose malabsorption should not take
    this medicinal product.
    The safety of apremilast was not evaluated in psoriatic arthritis or
    psoriasis patients with moderate or severe renal impairment in the
    clinical studies. OTEZLA® should be dose reduced to 30 mg
    once daily in patients with severe renal impairment.
    Weight decrease: The mean observed weight loss in patients treated for
    up to 52 weeks with apremilast was 1.99 kg. A total of 14.3% of patients
    receiving apremilast had observed weight loss between 5-10% while 5.7%
    of the patients receiving apremilast had observed weight loss greater
    than 10%. None of these patients had overt clinical consequences
    resulting from weight loss. A total of 0.1% of patients treated with
    apremilast discontinued due to adverse reaction of weight decreased.
    Patients who are underweight at the start of treatment should have their
    body weight monitored regularly. In the event of unexplained and
    clinically significant weight loss, these patients should be evaluated
    by a medical practitioner and discontinuation of treatment should be
    considered.
    Pregnancy: Pregnancy should be excluded before treatment can be
    initiated. Women of childbearing potential should use an effective
    method of contraception to prevent pregnancy during treatment.
    Summary of the safety profile
    The most commonly reported adverse reactions in Phase III clinical
    studies have been gastrointestinal (GI) disorders including diarrhoea
    (15.7%) and nausea (13.9%). These GI adverse reactions were mostly mild
    to moderate in severity, with 0.3% of diarrhoea and 0.3% of nausea
    reported as being severe. These adverse reactions generally occurred
    within the first 2 weeks of treatment and usually resolved within 4
    weeks. The other most commonly reported adverse reactions included upper
    respiratory tract infections (8.4%), headache (7.9%), and tension
    headache (7.2%). Overall, most adverse reactions were considered to be
    mild or moderate in severity.
    The most common adverse reactions leading to discontinuation during the
    first 16 weeks of treatment were diarrhoea (1.7%), and nausea (1.5%).
    The overall incidence of serious adverse reactions was low and did not
    indicate any specific system organ involvement. Hypersensitivity
    reactions were uncommonly observed in apremilast clinical studies.
    During the placebo-controlled period of the phase III clinical trials in
    psoriasis, 1.2% (14/1184) of patients treated with apremilast reported
    depression compared to 0.5% (2/418) treated with placebo. None of these
    reports of depression was serious or led to study discontinuation.
    Special populations
    No overall differences were observed in the safety profile of elderly
    patients ≥ 65 years of age and younger adult patients < 65 years of age
    in the clinical studies.
    The safety of apremilast was not evaluated in psoriatic arthritis or
    psoriasis patients with hepatic impairment.
    The safety and efficacy of apremilast in children aged 0 to 17 years
    have not been established. There is no data available.
    Please click here
    for Full Prescribing Information (EU Label)
    ADDITIONAL IMPORTANT SAFETY INFORMATION based on US labeling
    Therapeutic indications
    OTEZLA is approved in the U.S.:

    • For the treatment of adults with active psoriatic arthritis
    • For the treatment of patients with moderate to severe plaque psoriasis
      who are candidates for phototherapy or systemic therapy

    Contraindications
    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: Carefully weigh the risks and benefits of treatment with
    Otezla for patients with a history of depression and/or suicidal
    thoughts/behaviour, 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 Otezlais
      associated with an increase in adverse reactions of depression. During
      clinical trials, 1.3% (12/920) of patients treated with Otezla
      reported depression compared to 0.4% (2/506) on placebo; 0.1% (1/1308)
      of Otezla patients discontinued treatment due to depression compared
      with none on placebo (0/506). 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: 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.

    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% 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

    • 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 ≥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 Special 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 (US Label)
    ABOUT PSORIASIS AND PSORIATIC ARTHRITIS
    Psoriasis is known to affect around 14 million people in Europe. It is a
    chronic and systemic inflammatory skin disorder, and is immune-mediated,
    meaning it is caused by an immune reaction in the body.7
    Psoriasis lesions can often be found on areas close to the joints such
    as the elbows and knees but can also appear on the scalp.7
    Nail psoriasis affects up to 50% of people with psoriasis and up to 90%
    of people living with psoriatic arthritis.8,9 Up to
    84% of people with psoriasis experience itching, and over a third of
    patients actually cite itch as the most important factor contributing to
    their disease.10,11
    75% of people living with psoriasis believe it has a negative impact on
    their quality of life and 83% of patients with psoriasis actively
    conceal the visible signs of their disease.12,13
    Around a third of people living with psoriasis may go on to develop
    psoriatic arthritis, which affects the body in different ways to
    psoriasis and often causes pain, as well as swelling and tenderness
    particularly around the joints. It is clear that the two
    conditions are closely connected, and if left untreated, psoriatic
    arthritis can have a severe impact on mobility and physical function.14
    Two distinct physical symptoms of psoriatic arthritis are dactylitis
    (enlargement of the fingers, commonly referred to as “sausage fingers”)
    and enthesitis (inflammation at sites where tendons or ligaments insert
    into bone). A substantial number – 41% – of people living with
    psoriatic arthritis suffer from dactylitis in the fingers and also the
    toes, and enthesitis is known to affect up to 71% of patients.15
    People with psoriatic arthritis can often experience skin symptoms
    for up to 10 years before the onset of joint symptoms.16
    Diagnosing psoriatic arthritis can be a tricky process because its
    symptoms frequently mimic those of other forms of inflammatory
    arthritis, such as rheumatoid arthritis (RA) and gout. It can also be
    confused with osteoarthritis (OA), the most common form of arthritis.17
    ABOUT CELGENE
    Celgene International Sàrl, located in Boudry, in the Canton of
    Neuchâtel, Switzerland, is a wholly-owned subsidiary and International
    Headquarter 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 the Company’s website at www.celgene.com.
    Follow Celgene on Social Media: @Celgene,
    Pinterest,
    LinkedIn,
    FaceBook
    and YouTube.
    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.

    References
    1 Crowley, J. et al. Long-term Safety in Psoriasis and
    Psoriatic Arthritis Patients Treated With Apremilast: Pooled Analysis
    for ≥156 Weeks in the ESTEEM and PALACE 1-3 Phase 3 Trials (Abstract)
    2 Gottlieb, A. et al. Assessing Clinical Response and Minimal
    Disease Activity With the Physician Global Assessment and Body Surface
    Area Composite Tool: an Analysis of Apremilast Phase 3 ESTEEM Data
    (Abstract).
    3 Celgene data on file. 2016.
    4 Crowley, J. et al. Long-term Safety in Psoriasis and
    Psoriatic Arthritis Patients Treated With Apremilast: Pooled Analysis
    for ≥156 Weeks in the ESTEEM and PALACE 1-3 Phase 3 Trials (Poster)
    5 PH Schafer et al. Apremilast, a cAMP phosphodiesterase-4
    inhibitor, demonstrates anti-inflammatory activity in vitro and in a
    model of psoriasis. British Journal of Pharmacology (2010), 159, 842–855.
    6 Apremilast Summary of Product Characteristics, January 2015
    7 Augustin M and The European Expert Working Group for
    Healthcare in Psoriasis. A framework for improving the quality of care
    for people with psoriasis. JEADV 2012, 26 (Suppl. 4), 1–16.
    8 De Vries AC et al. Cochrane Database Syst Rev. 2013;
    1:CD007633
    9 Tan EST et al. Am J Clin Dermatol; 2012;
    13(6):375–388.
    10 Lebwohl MG et al.Patient perspectives in the
    management of psoriasis: Results from the population-based Multinational
    Assessment of Psoriasis and Psoriatic Arthritis Survey J Am Acad
    Dermatol
    2014;70:871−81
    11 Yosipovitch et al. Br J Dermatol. 2000;143:969.
    12 Bhosle M, Kulkarni A, Feldman S, Balkrishnan R. Quality of
    life in patients with psoriasis. Health Qual Life Outcomes. 2006;4(35)
    13 Armstrong et al. PLOS One. 2012;12:e52935.
    14 Gladman, DD et al. Psoriatic arthritis: epidemiology,
    clinical features, course and outcome. Ann Rheum Dis. 2005;64(Suppl
    II):ii14–ii17. doi: 10.1136/ard.2004.032482
    15 Ritchlin C et al. Ann Rheum Dis 2014; 73(6):990–999.
    16 World Psoriasis Day Consortium. Facts about Psoriasis. Accessed
    March 2015. (https://www.worldpsoriasisday.com/web/page.aspx?refid=129)
    17 Arthritis Foundation. Psoriatic Arthritis Diagnosis. https://www.arthritis.org/about-arthritis/types/psoriatic-arthritis/diagnosing.php

    clinical trialsclinical studieschronic plaque psoriasiseurope
    The Conversation (0)

    Latest News

    Outlook Reports

    Resource
    • Precious Metals
      • Gold
      • Silver
    • Battery Metals
      • Lithium
      • Cobalt
      • Graphite
    • Energy
      • Uranium
      • Oil and Gas
    • Base Metals
      • Copper
      • Nickel
      • Zinc
    • Critical Metals
      • Rare Earths
    • Industrial Metals
    • Agriculture
    Tech
      • Artificial Intelligence
      • Cybersecurity
      • Gaming
      • Cleantech
      • Emerging Tech
    Life Science
      • Biotech
      • Cannabis
      • Psychedelics
      • Pharmaceuticals

    Featured Biotech Investing Stocks

    More featured stocks

    Browse Companies

    Resource
    • Precious Metals
    • Battery Metals
    • Energy
    • Base Metals
    • Critical Metals
    Tech
    Life Science
    MARKETS
    COMMODITIES
    CURRENCIES
    ×