Brussels, Belgium – 28th May, 07:00 CEST – UCB announced today that the U.S. Food and Drug Administration (FDA) has approved extending the label for CIMZIA® (certolizumab pegol) to include a new indication in adults with moderate-to-severe plaque psoriasis. CIMZIA is indicated for the treatment of adults with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy. The approval makes CIMZIA the first Fc-free, PEGylated anti-TNF treatment option for this indication and marks the entry of UCB into immuno-dermatology, where significant unmet need currently exists. The approval also follows a recent FDA label update for CIMZIA in pregnancy and breastfeeding that provides essential information to healthcare professionals and women.
“The Phase 3 clinical development program for CIMZIA in plaque psoriasis demonstrated statistically significant improvements in efficacy endpoints at week 16. A clinically meaningful response was maintained up to week 48. This compelling body of evidence is especially significant for a disease like psoriasis, which often has significant emotional and social burdens in addition to the more widely recognized physical symptoms,” Alice Gottlieb, M.D., Ph.D., Professor of Dermatology at New York Medical College and lead investigator. “Today’s approval provides patients and their healthcare professionals with a robust new biologic option that provides durable disease control. The two dose regimens of CIMZIA also allow for patient-tailored treatment. CIMZIA also demonstrated similar efficacy in both biologic-naïve patients and those previously treated with other biologics.”
“CIMZIA is the first Fc-free biologic of its kind approved by the FDA to treat this challenging skin condition, building on 10 years of market experience with demonstrated efficacy and established safety across multiple inflammatory diseases. This approval reflects our heritage of making a difference for specific patient populations with unmet needs, and we are especially gratified to welcome immuno-dermatology patients for the first time to our community of support,” said Emmanuel Caeymaex, Head of Immunology and Executive Vice President, Immunology Patient Value Unit, UCB. “The approval of CIMZIA for psoriasis and the recent CIMZIA label update regarding pregnancy and breastfeeding in women with chronic inflammatory diseases are important treatment advances.UCB is committed to improving care for psoriasis patients and is also investigating bimekizumab, a therapy with significant potential for psoriasis patients.”
This FDA approval is based on data from a Phase 3 clinical development program consisting of CIMPASI-1, CIMPASI-2 and CIMPACT. The trials enrolled over 1,000 patients, of whom nearly one third had prior biologic exposure, and confirmed the durable efficacy up to 48 weeks and safety of CIMZIA in the treatment of adults 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% and 90% or greater disease improvement from baseline, as measured by the Psoriasis Area and Severity Index (PASI 75 and PASI 90, respectively) compared to placebo; within 16 weeks in CIMPASI-1 and CIMPASI-2, and within 12 weeks in CIMPACT. CIMPASI-1, CIMPASI-2 and CIMPACT 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. In all three trials, CIMZIA demonstrated statistically significant improvements for all primary and co-primary endpoints compared to placebo at all tested doses, and the clinical benefit was maintained through to week 48.1 These findings and the new approval in psoriasis that they support are significant because they build on four years of efficacy and safety data in psoriatic arthritis (PsA).2
According to the updated label, the recommended dose of CIMZIA for adults with moderate-to-severe plaque psoriasis is 400 mg (given as two subcutaneous injections of 200 mg each) every other week. For some patients (with body weight ≤ 90 kg), CIMZIA 400 mg (given as two subcutaneous injections of 200 mg each) initially and at Weeks 2 and 4, followed by 200 mg every other week can be considered.
“Due to the unique nature of psoriasis, it is critical for dermatologists to have as many options as possible to find the right treatment for each patient, said Michael Siegel, Ph.D., Senior Vice President of Research and Clinical Affairs, National Psoriasis Foundation. “It’s a great day when new psoriasis treatments come to market, as both dermatologists and patients are given hope that this could be the treatment that will work for them.”
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.3
Psoriasis affects nearly three percent of the population, or approximately 125 million people worldwide.3 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.4 As many as 42% of patients with psoriasis will develop psoriatic arthritis,5,6 33% will develop metabolic syndrome,7 and approximately 46% are often or always depressed because of their psoriasis.8 Despite drug development advances in the past decade, patient survey data suggest that moderate-to-severe psoriasis is being undertreated.9
About the CIMPASI-1, CIMPASI-2 and CIMPACT Studies1
CIMPASI-1, CIMPASI-2 and CIMPACT Phase 3 trials each evaluated the efficacy and safety of CIMZIA (certolizumab pegol, CZP) in adults 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 75% and 82% for patients receiving CZP 400 mg every two weeks (Q2W) and 65% and 81% for patients receiving CZP 200 mg every two weeks (Q2W), compared to 7% and 13% for patients receiving placebo, respectively. The response rate for patients who achieved a PASI 90 response was 44% and 52% for patients receiving CZP 400 mg every Q2W and 36% and 50% for patients receiving CZP 200 mg Q2W, comparted to 0% and 5% for patients receiving placebo, respectively. In addition, the response rates 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 55% and 65% for CZP 400 Q2W dose-treated subjects, and 45% and 61% for CZP 200 mg Q2W dose-treated patients, compared to 4% and 3% for subjects receiving placebo, respectively. Week 16 PASI 75 responders maintained a PASI 75 response to week 48 in 94% and 81% of patients receiving CZP 400mg Q2W, and 81% and 74% for patients receiving CZP 200 mg Q2W, respectively.
In CIMPACT, the response rate for patients who achieved a PASI 75 response at week 16 was 69% and 75% among patients receiving CZP 400 mg Q2W and CZP 200 mg Q2W, compared to 4% for patients receiving placebo, respectively. The response rate for patients who achieved a PASI 90 at week 16 was 49% and 40% among patients receiving CZP 400 mg Q2W and CZP 200 mg Q2W, compared to 0% for patients receiving placebo. In patients who received CZP 400 mg Q2W and were PASI 75 responders at week 16, 98% maintained their response at week 48. In addition, 80% of patients who received CZP 200 mg Q2W from week 16 maintained their response at week 48.
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 safety profile for CIMZIA in other approved indications. In the placebo-controlled portions of the clinical trials in psoriasis patients, elevated liver enzymes were reported more frequently in the CIMZIA-treated patients than in placebo-treated patients, 4.3% in the 200mg group, 2.3% in the 400mg group, and 2.5% in placebo. Additionally, cases of other psoriasis subtypes were reported (including erythrodermic, pustular, and guttate) in <1% of CIMZIA-treated patients.
About the CRIB Study10
CRIB was a pharmacokinetic study assessing the potential level of placental transfer of certolizumab pegol (CZP) from pregnant women to their infants. The study followed 16 women (≥ 30 weeks gestation) who were already receiving CZP at approved doses. In the US, CIMZIA is not indicated for axial spondylitis (axSpA).
The study found that CZP levels were below the lower limit of quantification (LLOQ = 0.032 micrograms/ML) in 13 out of 15 infant blood samples at birth, and in all samples at weeks four and eight. One infant had a minimal CZP level of 0.042ug/ML, which was 0.09% of the mother’s plasma concentration at birth. In a second infant, delivered by emergency Caesarean section, the concentration was 0.485 mcg/mL, which was 4.49% of the mother’s plasma concentration at birth. At Week 4 and Week 8, all 15 infants had no measurable concentrations. No anti-CZP antibodies were detected in mothers, umbilical cords, or infants. Among 16 exposed infants, one serious adverse reaction was reported in a neonate who was treated empirically with intravenous antibiotics due to an increased white blood cell count; blood cultures were negative. These data indicate negligible to low placental transfer of CZP from mothers to infants, suggesting minimal in-utero fetal exposure during the third trimester.
About the CRADLE Study4
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 breastfeeding infant.
Among 137 breast milk samples from 17 mothers, 56% had no measurable CZP; the remaining samples showed minimal levels of CZP. The median of the estimated average daily infant doses was 0.0035 mg/kg/day (range: 0 to 0.01 mg/kg/day). The percentage of the maternal dose (200 mg CIMZIA dosed once every 2 weeks), that reaches an infant ranged from 0.56% to 4.25% based on samples with measurable certolizumab pegol concentration.
In CRADLE, no serious adverse reactions were noted in the 17 infants in the study. Adverse events in mothers exposed to CZP were consistent with the known safety profile of CZP.
About CIMZIA® in the US
CIMZIA® is the only Fc-free, PEGylated anti-TNF (Tumor Necrosis Factor). CIMZIA® has a high affinity for human TNF-alpha, selectively neutralizing the pathophysiological effects of TNF-alpha.
CIMZIA® is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis, adults with active psoriatic arthritis (PsA), and adults with active ankylosing spondylitis (AS).
In addition, it is indicated for reducing signs and symptoms of Crohn’s disease (CD) and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy. See important safety information including risk of serious bacterial, viral and fungal infections and tuberculosis below.
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.