Health Canada Approves CIMZIA® (certolizumab pegol) for Moderate-to-Severe Psoriasis

Health Canada also approves Label Updates in Pregnancy and Breastfeeding

OAKVILLE, ON, March 25, 2019 /CNW/ - UCB Canada Inc. announced today that Health Canada has approved a new indication for CIMZIA® (certolizumab pegol) for the treatment of adult patients with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy.ⁱ The approval makes CIMZIA the first Fc-free, PEGylated anti-TNF option available for the treatment of the disease where significant unmet need currently exists. UCB Canada Inc. also announced that Health Canada has approved label updates in pregnancy and breastfeeding based on two pivotal pharmacokinetic studies.^ii,iii This marks a major advance for Canadian women of all ages living with plaque psoriasis and other autoimmune diseases.

"The approval of a new and effective treatment option in plaque psoriasis with demonstrated durable and flexible disease control is welcome news for Canadian patients and physicians," said Dr. Wayne Gulliver, B.Sc., B.Med.Sc., M.D., FRCPC, dermatologist and Professor of Medicine (Dermatology) at Memorial University in St. John's, Newfoundland. "CIMZIA's similar efficacy in both biologic-naïve patients and those previously treated with other biologics also helps meet an unmet need in this area."

Psoriasis is a common chronic inflammatory skin condition that impacts more than one million Canadians^iv of all ages and about 125 million people worldwide.^v There is currently no cure for psoriasis and patients may experience recurrence of symptoms throughout their life. The disease affects both men and women, with about 75 per cent of psoriasis cases in women occurring before the age of 40.^vi Therefore, psoriasis may impact women during a critical time when many are planning for families.^vii

"For people living with plaque psoriasis, this is a welcome new treatment option to help them manage their disease," said Kathryn Andrews-Clay, Executive Director, Canadian Association of Psoriasis Patients. "Living with psoriasis can be isolating and, at times, stressful. Combine this with balancing treatment and planning for a family, or caring for a newborn, and it can be overwhelming. We are thrilled that with CIMZIA women now have an option to control their disease at any stage of their lives – including before, during and after pregnancy."

"The approval of CIMZIA for psoriasis, and label update regarding pregnancy and breastfeeding in women with autoimmune diseases, are important treatment advances which build on more than 10 years of market experience and proven efficacy and safety," said Lionel Houle, Head of Immunology, UCB Canada Inc."Today's announcement reflects our heritage of making a difference for specific patient populations with unmet needs. Many women living with autoimmune diseases would benefit from a clearer understanding of the impact treatment can have on their baby, flare management during pregnancy and breastfeeding, and whether to restart treatment after pregnancy."

Health Canada's approval for the treatment of adult patients with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy is based on data from a Phase 3 clinical development program consisting of CIMPASI-1, CIMPASI-2 and CIMPACT. The trials enrolled a total of 1,020 patients, ≥ 18 years of age 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.^viii 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 coprimary endpoints compared to placebo at all tested doses, and the clinical benefit was maintained through to week 48. 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).

According to the updated label, the recommended dose of CIMZIA for adults with moderate-to-severe plaque psoriasis is 400 mg every other week (given as two subcutaneous injections of 200 mg each). A dose of 400 mg initially (week 0) and at Weeks 2 and 4 followed by 200 mg every 2 weeks may be considered.

About Psoriasis
Psoriasis is a common chronic inflammatory skin condition. 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.^ix

Psoriasis affects nearly three percent of the population, or approximately 125 million people worldwide.^x 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.^xi

As many as 42% of patients with psoriasis will develop psoriatic arthritis,^xii,xiii 33% will develop metabolic syndrome,[xiv] and approximately 46% are often or always depressed because of their psoriasis.^xv Despite drug development advances in the past decade, patient survey data suggest that moderate-to-severe psoriasis is being undertreated.^xvi

About the CIMPASI-1, CIMPASI-2 and CIMPACT Studies^xvii
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, compared 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 pro􀁾le 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 Study^xviii
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.

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 Study^xix
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 Canada^xx
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 TNFalpha.

CIMZIA in combination methotrexate (MTX) is indicated for reducing signs and symptoms, inducing major clinical response, and reducing the progression of joint damage as assessed by X-ray, in adult patients with moderately-to-severely active rheumatoid arthritis (RA). CIMZIA may be used alone for reducing signs and symptoms in adult patients with moderately- to -severely active rheumatoid arthritis (RA) who do not tolerate MTX.

CIMZIA alone or in combination with MTX is indicated for reducing signs and symptoms and inhibiting the progression of structural damage as assessed by X-ray, in adult patients with moderately-to-severely active psoriatic arthritis (PsA) who have failed one or more disease-modifying anti-rheumatic drugs (DMARDs).

CIMZIA is also indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis (AS) who have had an inadequate response to conventional therapy.

CIMZIA is approved for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy.

Important and complete safety information about CIMZIA can be found by accessing the product monograph at: https://www.ucb-canada.ca/_up/ucbpharma_ca_en/documents/Cimzia-PM-WOCBA-approved-en-08feb2019.pdf

About UCB Canada Inc.
Inspired by patients and driven by science, UCB Canada Inc. is a biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe autoimmune and central nervous system diseases. For more information, please consult https://www.ucb-canada.ca/

References

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ⁱ CIMZIA Product Monograph. February 8, 2019

ⁱⁱ Mariette X, Förger F, Abraham B, et al. Lack of Placental Transfer of Certolizumab Pegol During Pregnancy: Results from CRIB, a Prospective, Postmarketing, Multicentre, Pharmacokinetic Study. Ann Rheum Dis. 2018:77(2):228-233

ⁱⁱⁱ Clowse ME, Förger F, Hawng C, et al. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a Prospective, Postmarketing, Multicentre, Pharmacokinetic study. Ann Rheum Dis. 2017;76: 1890-1896

^iv Canadian Association of Psoriasis Patients. Pso Serious 2018: A Report on Access to Care and Treatment for Psoriasis Patients in Canada http://psoserious.ca/wp-content/uploads/2018/10/CAPP_2018_Report_Final.pdf. Last accessed on February 20, 2019

^v International Federation of Psoriasis Associations https://ifpa-pso.com/our-cause/ Last accessed on February 20, 2019

^vi Tauscher AE, Fleischer AB Jr, Phelps KC, et al. Psoriasis and pregnancyJ Cutan Med Surg. 2002;6(6):561-570

^vii Tauscher AE, Fleischer AB Jr, Phelps KC, et al. Psoriasis and pregnancyJ Cutan Med Surg. 2002;6(6):561-570

^viii UCB data on file

^ix Canadian Association of Psoriasis Patients. Psoriasis Symptoms http://www.canadianpsoriasis.ca/index.php/en/psoriasis/81-english/psoriasis/94-symptoms. Last accessed on February 20, 2019

^x International Federation of Psoriasis Associations https://ifpa-pso.com/our-cause/ Last accessed on February 20, 2019

^xi National Psoriasis Foundation. How Severe Is My Psoriasis? https://www.psoriasis.org/about-psoriasis Last accessed on February 20, 2019

^xii Mease PJ and Armstrong AW. Managing Patients with Psoriatic Disease: The Diagnosis and Pharmacologic Treatment of Psoriatic Arthritis in Patients with Psoriasis. Drugs. 2014;74(4):423-41

^xiii Gladman DD, Antoni C, Mease P, et al. Psoriatic arthritis: epidemiology, clinical features,course, and outcome. Ann Rheum Dis. 2005;64 Suppl 2:ii14-7

^xiv Danielsen K, Wilsgaard T, Olsen AO, et al. Elevated odds of metabolic syndrome in psoriasis: a population-based study of age and sex differences*. British Journal of Dermatology. 2015;172:419–427

^xv Weiss SC, Kimball AB, Liewehr DJ, et al. Quantifying the harmful effect of psoriasis on health-related quality of life. J Am Acad Dermatol. 2002;47:512-518

^xvi Lebwohl MG, Bachelez H, Barker J, 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(5):871-881

^xvii UCB data on file

^xviii Mariette X, Förger F, Abraham B, et al. Lack of Placental Transfer of Certolizumab Pegol During Pregnancy: Results from CRIB, a Prospective, Postmarketing, Multicentre, Pharmacokinetic Study. Ann Rheum Dis. 2018:77(2):228-233

^xix Clowse ME, Förger F, Hawng C, et al. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a Prospective, Postmarketing, Multicentre, Pharmacokinetic study. Ann Rheum Dis. 2017;76:1890–1896

^xx CIMZIA Product Monograph. February 8, 2019

SOURCE UCB Canada Inc.

Ben Faienza, UCB Canada Inc., Tel: [phone], [email protected]