UCB Announces Positive CHMP Opinion for CIMZIA® (certolizumab pegol) in Patients with Moderate-to-Severe Plaque Psoriasis

Brussels (ots/PRNewswire) – Strictly not for UK/Irish media

* CIMZIA® (certolizumab pegol) Phase 3 psoriasis data demonstrated significant and clinically meaningful improvements in biologic-naïve and previously treated patients, with clinical benefit maintained up to one year[1]

* This milestone represents UCB’s entry into immuno-dermatology,
where there is significant unmet patient need

* This follows a recent European Medicines Agency (EMA) label update for CIMZIA in pregnancy and breastfeeding, making CIMZIA the first anti-TNF for potential use in women during both pregnancy and lactation in its approved indications[2]

UCB today announced that the European Committee for Medicinal Products for Human Use (CHMP) has recommended approval of a label extension for CIMZIA® (certolizumab pegol), to include a new indication in adult patients with moderate-to-severe plaque psoriasis.[3] CIMZIA is the first Fc-free, PEGylated anti-TNF to receive a positive CHMP opinion for use in moderate-to-severe plaque psoriasis.[3] The European Commission’s (EC) endorsement of the CHMP positive opinion for psoriasis is expected in the second quarter of 2018 and would further broaden the clinical value of CIMZIA.

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“The Phase 3 clinical development program for CIMZIA in plaque psoriasis demonstrated clinically meaningful improvements in primary efficacy endpoints over a 48-week period, as well as improvements in important patient quality of life measures. The data established the durable clinical benefit of CIMZIA, with all three studies showing that the clinical benefit with CIMZIA was maintained for up to one year. Psoriasis has a significant emotional and physical impact on patients, and there is still a need for new therapies that effectively control skin symptoms over time. The availability of CIMZIA in psoriasis would provide healthcare professionals with an effective, broad spectrum anti-TNF with 10 years of clinical experience to help manage this debilitating condition and improve the quality of patients’ lives through durable disease control,” said Diamant Thaçi, Professor, MD, Director of the Institute for Inflammatory Medicine, University Hospital Schleswig-Holstein, Campus Lübeck.

“CIMZIA is the first anti-TNF of its kind to receive a CHMP positive opinion for this challenging disease. We look forward to offering patients and their dermatologists a new treatment option, with best-in-class efficacy and two different doses to maximize disease control, achieve clear skin and face the serious quality-of-life challenges that often accompany plaque psoriasis. This new indication is particularly relevant following the CIMZIA label update for pregnancy and breastfeeding, as a significant proportion of patients with moderate to severe plaque psoriasis are women, making CIMZIA an optimal treatment for women of childbearing age,” said Emmanuel Caeymaex, Head of Immunology and Executive Vice President, Immunology Patient Value Unit, UCB.

The CHMP positive opinion is based on data from a Phase 3 clinical development program consisting of CIMPASI-1, CIMPASI-2 and CIMPACT. The trials, which enrolled over 1,000 patients, with and without prior treatment experience with biologic products, confirmed the efficacy and safety of CIMZIA in the treatment of adult patients with moderate-to-severe plaque psoriasis.[1] Each of the three studies included an assessment of the percentage of patients who achieved at least 75% or greater disease improvement from baseline as measured by the Psoriasis Area and Severity Index (PASI 75) compared to placebo; within 16 weeks in CIMPASI-1 and CIMPASI-2, and within 12 weeks in CIMPACT. CIMPASI-1 and CIMPASI-2 also assessed the percentage of patients who achieved at least a two-point improvement on a five-point Physician’s Global Assessment (PGA) scale to a final score representing clear or almost clear skin, each compared with placebo, at week 16 as a co-primary endpoint. In all three trials, CIMZIA demonstrated statistically significant improvements for all primary and co-primary endpoints compared to placebo at all treatment doses, and the clinical benefit was maintained through to week 48.[1]

According to the updated label, the recommended starting dose of CIMZIA for adult patients is 400 mg at weeks 0, 2 and 4. After the starting dose, the maintenance dose of CIMZIA for adult patients with plaque psoriasis is 200 mg every 2 weeks. A dose of 400 mg every 2 weeks can be considered in patients with insufficient response.[3]

Additionally, the recent European Medicines Agency (EMA) label update for CIMZIA in pregnancy and breastfeeding, makes CIMZIA the first anti-TNF for potential use in women during both pregnancy and lactation in its approved indications.[2] The update included specific pregnancy and lactation information, based on findings from two first-of-their-kind studies, CRIB and CRADLE, together with pregnancy outcomes data.[2],[4],[5] Results from the UCB-sponsored CRIB study, a prospective pharmacokinetic study, demonstrated no to minimal placental transfer of CIMZIA from mother to child during pregnancy.[4] Data from CRADLE, a prospective pharmacokinetic study, found minimal transfer of CIMZIA into breast milk during lactation.[5] Both studies included a safety evaluation.[4],[5] CIMZIA is also approved for the treatment of psoriatic arthritis (PsA), a frequent co-morbidity of psoriasis patients.[2],[6]

About Psoriasis

Psoriasis is a common, chronic inflammatory disease with primary involvement of the skin. The skin condition affects men and women of all ages and ethnicities. Psoriasis signs and symptoms can vary, but may include red patches of skin covered with silvery scales, dry, cracked skin that may bleed and thickened, pitted or ridged nails.[7]

Psoriasis affects nearly three per cent of the population, or approximately 125 million people worldwide.[7] Symptoms vary from person to person, but for those who are more severely affected, psoriasis can have a major impact on their quality of life.[7] As many as 42% of patients with psoriasis will develop PsA,[8],[9] 33% will develop metabolic syndrome[10] and approximately 46% are often or always depressed because of their psoriasis.[11] Despite drug development advances in the past decade, patient survey data suggest that moderate-to-severe psoriasis is being undertreated.[12]

In pregnancy, psoriasis can present a number of challenges, with 23% of women experiencing a worsening of symptoms during pregnancy.[13] Multiple studies have shown that psoriasis can contribute to an increased risk of adverse pregnancy outcomes including preterm delivery, low birth weight, spontaneous abortion, caesarean delivery, and babies that are large for gestational age and of higher than average birth weight.[14],[15],[16] In addition, up to 65% of women with psoriasis experience a worsening of psoriasis symptoms postpartum.[13] Controlling psoriasis before, during and after pregnancy is important for the health of both mother and baby.[17]

About the CIMPASI-1, CIMPASI-2 and CIMPACT Studies[1]

CIMPASI-1, CIMPASI-2 and CIMPACT Phase 3 trials each evaluated the efficacy and safety of CIMZIA (certolizumab pegol, CZP) in adult patients with moderate-to-severe plaque psoriasis. The three trials enrolled approximately 1,000 patients, including patients with and without prior treatment experience with biologic products.

In CIMPASI-1 and CIMPASI-2, at week 16, the response rate for patients who achieved a PASI 75 response was 66.5% and 81.4% for patients receiving CZP 200 mg every two weeks (Q2W), and 75.8% and 82.6% for patients receiving CZP 400 mg every two weeks (Q2W), compared to 6.5% and 11.6% for patients receiving placebo, respectively. In addition, the response rate for patients achieving at least a two-point improvement to a final score of clear or almost clear skin on the PGA scale (PGA 0/1) at week 16 was 47.0% and 66.8% for CZP 200 mg Q2W dose-treated patients, and 57.9% and 71.6% for CZP 400 mg Q2W dose-treated patients, compared to 4.2% and 2.0% for patients receiving placebo, respectively. Responder rates for maintenance of a PASI 75 response to week 48 were 67.2% and 78.7% for patients receiving CZP 200 mg Q2W, and 87.1% and 81.3% for patients receiving CZP 400 mg Q2W, respectively. Responder rates for maintenance of a PGA 0/1 score through to week 48, were 52.7% and 72.6% for patients receiving CZP 200 mg Q2W, and 69.5% and 66.6% for patients receiving CZP 400 mg Q2W, respectively.

In CIMPACT, the response rate for patients who achieved a PASI 75 response at week 12, was 61.3% and 66.7% and among patients receiving CZP 200 mg Q2W and CZP 400 mg Q2W, compared to 5.0% for patients receiving placebo, respectively. In patients who received CZP 200 mg Q2W and were PASI 75 responders at week 16, 80.0% of patients who remained on CZP 200 mg Q2W maintained their response at week 48, and 98.0% of patients who then received CZP 400 mg Q2W from week 16 maintained their response at week 48.

In response to the recognized impact of psoriasis on patient experience, improvements in Dermatology Life Quality Index (DLQI) were also observed in all three trials at week 16, and maintained through to week 48. DLQI is a widely used and recognized quality of life measurement instrument used across several dermatological diseases.

In all three trials, CIMZIA demonstrated statistically significant improvements for all primary or co-primary endpoints compared to placebo at all treatment doses, and the clinical benefit was maintained through to 48 weeks. The adverse event profile across all three trials appears consistent with the known safety profile of anti-TNF therapy and no new safety signals were observed with CIMZIA at any dose over 48 weeks.

About the CRIB Study[4]

CRIB was a pharmacokinetic study assessing the potential level of placental transfer of CZP from pregnant women to their infants. The study followed sixteen women (>= 30 weeks gestation) who were already receiving CZP 200 mg Q2W or 400 mg Q4W for locally approved indications, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondylitis (axSpA) or Crohn’s Disease (CD). CRIB did not include any patients suffering from psoriasis nor patients treated with a CZP 400 mg Q2W dose. In the EU, CIMZIA is not indicated in CD.

The study found that CZP levels were below the lower limit of quantification in 13 out of 14 infant blood samples at birth, and in all samples at weeks four and eight. One infant had a minimal CZP level of 0.042µg/mL (infant/mother plasma ratio 0.0009%). No anti-CZP antibodies were detected in mothers, umbilical cords, or infants. These data indicate no to minimal placental transfer of CZP from mothers to infants, suggesting lack of in utero fetal exposure during the third trimester.

In CRIB, adverse events experienced by the infants did not show any patterns or clusters of events suggesting a specific safety signal in children. Safety data in the mothers were in line with the known safety profile of CZP and pregnancy profile of these underlying diseases.

About the CRADLE Study[5]

The primary objectives of the CRADLE pharmacokinetic study were to determine the concentration of CZP in human breast milk and the average daily infant dose, an estimation of the daily dose of maternal CZP ingested by the infant over the dosing interval.

The study followed 17 lactating women who were already receiving CZP 200 mg Q2W or 400 mg Q4W suffering from RA, PsA, axSpA or CD. CRADLE did not include any patients suffering from psoriasis nor patients treated with a CZP 400 mg Q2W dose.

Among 137 breast milk samples from 17 mothers, all samples had CZP concentrations that were minimal, less than 3 times the lower limit of quantification and less than 1% of the plasma concentration expected with a therapeutic dose. A post-hoc analysis of the relative infant dose (RID) of CZP in breast milk was calculated and ranged from 0.04% to 0.30%. The RID is a useful parameter for assessing drug safety in breastfeeding and experts consider a RID that is less than 10% to be unlikely of concern to infant wellbeing.

In CRADLE, adverse events in the infants of mothers exposed to CZP were consistent with those occurring in unexposed infants of similar age. Adverse events in mothers exposed to CZP were consistent with the known safety profile of CZP.

About CIMZIA® in the EU/EEA

In the EU, CIMZIA® in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active RA in adult patients inadequately responsive to disease-modifying anti-rheumatic drugs (DMARDs) including MTX.

CIMZIA can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. CIMZIA in combination with MTX is also indicated for the treatment of severe, active and progressive RA in adults not previously treated with MTX or other DMARDs.

CIMZIA has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with MTX.

CIMZIA, in combination with MTX, is also indicated for the treatment of active psoriatic arthritis in adults when the response to previous DMARD therapy has been inadequate. CIMZIA can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate.

CIMZIA is also indicated in the EU for the treatment of adult patients with severe active axial spondyloarthritis (axSpA), comprising:

* Ankylosing spondylitis (AS) – adults with severe active AS who have had an inadequate response to, or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs).

* Axial spondyloarthritis (axSpA) without radiographic evidence of AS

* adults with severe active axSpA without radiographic evidence of
AS but with objective signs of inflammation by elevated C-reactive protein (CRP) and/or Magnetic Resonance Imaging (MRI) who have had an inadequate response to, or are intolerant to NSAIDs.

About CIMZIA® in Fertility, Pregnancy and Lactation in the EU/EEA

Women of childbearing potential

The use of adequate contraception should be considered for women of childbearing potential. For women planning pregnancy, continued contraception may be considered for 5 months after the last CIMZIA dose due to its elimination rate, but the need for treatment of the woman should also be taken into account (see below).

Pregnancy

Data from more than 500 prospectively collected pregnancies exposed to CIMZIA with known pregnancy outcomes, including more than 400 pregnancies exposed during the first trimester, does not indicate a malformative effect of CIMZIA. However, the available clinical experience is too limited to, with a reasonable certainty, conclude that there is no increased risk associated with CIMZIA administration during pregnancy.

Animal studies using a rodent anti

, UCB:
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