New UCB Data Provide Clinical Insights Into the Use of Cimzia® (certolizumab pegol) in Treating Crohn's Disease

ATLANTA, Oct. 19, 2015 /PRNewswire/ -- UCB, a global biopharmaceutical company focusing on immunology and neurology treatment and research, is sponsoring several data presentations on Cimzia^® (certolizumab pegol) in Crohn's disease at the American College of Gastroenterology (ACG) 2015 Annual Scientific Meeting, taking place in Honolulu, HI from October 16-21. The posters present pooled analyses of safety studies as well as new data examining the impact of anti-drug antibodies among patients exposed up to seven years in the PRECiSE 3 open-label extension trial evaluating Cimzia^® in Crohn's disease.

"UCB continues to support research that deepens our understanding of the role of Cimzia^® in treating Crohn's disease seven years after its U.S. approval," said Emmanuel Caeymaex, Head, Immunology Patient Value Unit, UCB. "These new data provide important clinical insights that will help physicians make the most informed and individualized treatment decisions for their Crohn's patients."

In the U.S., Cimzia^® is indicated for reducing signs and symptoms of Crohn's disease 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.

Posters on Cimzia for Crohn's Disease at ACG

• Transient Anti-Drug Antibodies and Their Impact on Markers of Inflammation: Longitudinal Data from a 7-Year Study of Certolizumab Pegol in Crohn's Disease Patients
  • Presentation Number: P1071
  • Presentation Date: Monday, October 19
  • Presentation Time: 10:00 a.m. – 3:30 p.m.
• Long-term Safety and Efficacy of Certolizumab Pegol Therapy in Patients with Moderate to Severe Crohn's Disease: 5-year Results
  • Presentation Number: P1745
  • Presentation Date: Tuesday, October 20
  • Presentation Time: 9:30 a.m. – 3:30 p.m
• Comparison of Cardiovascular Events in Older and Younger Crohn's Disease Patients Treated with Certolizumab Pegol: Results from a Pooled Safety Analysis
  • Presentation Number: P1043
  • Presentation Date: Monday, October 19
  • Presentation Time: 10:00 a.m. – 3:30 p.m
• Incidence of Benign and Malignant Neoplasms in Crohn's Disease Patients Aged ≤30 years versus 30-64 Years Treated with Certolizumab Pegol: Results from a Pooled Safety Analysis of 15 Studies
  • Presentation Number: P1052
  • Presentation Date: Monday, October 19
  • Presentation Time: 10:00 a.m. – 3:30 p.m
• Safety Profile of Extraintestinal Manifestations of Crohn's Disease During Treatment with Certolizumab Pegol
  • Presentation Number: P1053
  • Presentation Date: Monday, October 19
  • o   Presentation Time: 10:00 a.m. – 3:30 p.m

About the PRECiSE Clinical Trial Program^{1,2,3,4,5,6,7}
PRECiSE (PEGylated antibody fragment evaluation in Crohn's disease: safety and efficacy), one of the largest, most comprehensive clinical programs for an anti-TNF for moderate to severe Crohn's disease, is composed of two placebo-controlled studies (PRECiSE 1 and 2) and two open-label safety follow-up studies.  In the PRECiSE 1 and 2 clinical trials, which served as the basis for FDA approval of CIMZIA^®  for Crohn's disease, the primary efficacy endpoints of clinical response were evaluated using the Crohn's Disease Activity Index (CDAI) and defined as a decrease in CDAI score of ≥ 100 points.  CDAI is a weighted, composite index of eight items, which requires daily completion of a diary card and calculation of various weighting factors for one week.  In 2007, the two former studies were published in the New England Journal of Medicine (NEJM).  The studies demonstrated that more adult patients with moderate to severe Crohn's disease achieved and maintained clinical response with CIMZIA^® for up to 6 months, compared to placebo.  In a follow-up open-label extension safety study (PRECiSE 3), patients continued to receive CIMZIA^® 400 mg every 4 weeks for up to 7 years.  The Harvey-Bradshaw Index (HBI), which only requires scoring from the day before the study visit and involves a lower number of components, was used to evaluate Crohn's disease activity in PRECiSE 3. In a second follow-up open-label extension safety study (PRECiSE 4), the long-term outcomes of a re-induction regimen with CIMZIA^® were evaluated in patients who had experienced Crohn's disease exacerbation while receiving CIMZIA^® treatment during PRECiSE 1 and 2 studies.

About Crohn's Disease⁸
Crohn's disease is a type of inflammatory bowel disease (IBD), which is chronic, progressive, and often destructive. It causes inflammation of the gastrointestinal (GI) tract, most commonly affecting the end of the small intestine (the ileum) and the beginning of the large intestine (the colon). Crohn's disease has been estimated to affect as many as 700,000 Americans. Symptoms of Crohn's disease often include diarrhea, abdominal pain, and weight loss. People with Crohn's can experience an ongoing cycle of flare-up and remission throughout their lives. If not effectively treated, ongoing disease activity may result in the need for surgery and hospitalization.

About CIMZIA^®
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 reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy. In addition, it is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis, for the treatment of adults with active psoriatic arthritis (PsA) and for adults with active ankylosing spondylitis (AS). See important safety information including risk of serious bacterial, viral and fungal infections and tuberculosis below.

Important Safety Information about CIMZIA^® in the US⁹

Risk of Serious Infections and Malignancy

Patients treated with CIMZIA^® are at an increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. CIMZIA^® should be discontinued if a patient develops a serious infection or sepsis. Reported infections include:

• Active tuberculosis, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent tuberculosis before CIMZIA^® use and during therapy. Treatment for latent infection should be initiated prior to CIMZIA^® use.
• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
• Bacterial, viral and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with CIMZIA^® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIMZIA^®, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA^® is a member. CIMZIA^® is not indicated for use in pediatric patients.

Patients treated with CIMZIA^® are at an increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease.

Treatment with CIMZIA^® should not be initiated in patients with an active infection, including clinically important localized infections. CIMZIA^® should be discontinued if a patient develops a serious infection or sepsis. Patients greater than 65 years of age, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants (e.g., corticosteroids or methotrexate) may be at a greater risk of infection. Patients who develop a new infection during treatment with CIMZIA^® should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for immunocompromised patients, and appropriate antimicrobial therapy should be initiated. Appropriate empiric antifungal therapy should also be considered while a diagnostic workup is performed for patients who develop a serious systemic illness and reside or travel in regions where mycoses are endemic.

Malignancies

During controlled and open-labeled portions of CIMZIA^® studies of Crohn's disease and other diseases, malignancies (excluding non-melanoma skin cancer) were observed at a rate of 0.5 per 100 patient-years among 4,650 CIMZIA^®-treated patients versus a rate of 0.6 per 100 patient-years among 1,319 placebo-treated patients. In studies of CIMZIA^® for Crohn's disease and other investigational uses, there was one case of lymphoma among 2,657 CIMZIA^®-treated patients and one case of Hodgkin lymphoma among 1,319 placebo-treated patients. In CIMZIA^® RA clinical trials (placebo-controlled and open label), a total of three cases of lymphoma were observed among 2,367 patients. This is approximately 2-fold higher than expected in the general population. Patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of TNF blocker therapy in the development of malignancies is not known.

Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy ≤18 years of age), of which CIMZIA^® is a member. Approximately half of the cases were lymphoma (including Hodgkin's and non-Hodgkin's lymphoma), while the other cases represented a variety of different malignancies and included rare malignancies associated with immunosuppression and malignancies not usually observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants.

Cases of acute and chronic leukemia have been reported with TNF-blocker use. Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for developing leukemia.

Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma that has a very aggressive disease course and is usually fatal, have been reported in patients treated with TNF blockers, including CIMZIA^®.  The majority of reported TNF blocker cases occurred in adolescent and young adult males with Crohn's disease or ulcerative colitis.  Almost all of these patients had received treatment with the immunosuppressants azathioprine and/or 6-mercaptopurine (6-MP) concomitantly with a TNF blocker at or prior to diagnosis.  Carefully assess the risks and benefits of treatment with CIMZIA^®, especially in these patient types.

Periodic skin examinations are recommended for all patients, particularly those with risk factors for skin cancer.

Heart Failure

Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. CIMZIA^® has not been formally studied in patients with CHF. Exercise caution when using CIMZIA^® in patients who have heart failure and monitor them carefully.

Hypersensitivity

Symptoms compatible with hypersensitivity reactions, including angioedema, dyspnea, hypotension, rash, serum sickness, and urticaria, have been reported rarely following CIMZIA^® administration.  Some of these reactions occurred after the first administration of CIMZIA^®.  If such reactions occur, discontinue further administration of CIMZIA^® and institute appropriate therapy.

Hepatitis B Reactivation

Use of TNF blockers, including CIMZIA^®, has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. Some cases have been fatal. Test patients for HBV infection before initiating treatment with CIMZIA^®. Exercise caution in prescribing CIMZIA^® for patients identified as carriers of HBV, with careful evaluation and monitoring prior to and during treatment. In patients who develop HBV reactivation, discontinue CIMZIA^® and initiate effective anti-viral therapy with appropriate supportive treatment.

Neurologic Reactions

Use of TNF blockers, including CIMZIA^®, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis, and with peripheral demyelinating disease, including Guillain-Barré syndrome. Rare cases of neurological disorders, including seizure disorder, optic neuritis, and peripheral neuropathy have been reported in patients treated with CIMZIA^®. Exercise caution in considering the use of CIMZIA^® in patients with these disorders.

Hematologic Reactions

Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia (e.g., leukopenia, pancytopenia, thrombocytopenia) has been infrequently reported with CIMZIA^®. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on CIMZIA^®. Consider discontinuation of CIMZIA^® therapy in patients with confirmed significant hematologic abnormalities.

Drug Interactions

An increased risk of serious infections has been seen in clinical trials of other TNF blocking agents used in combination with anakinra or abatacept. Formal drug interaction studies have not been performed with rituximab or natalizumab; however, because of the nature of the adverse events seen with these combinations with TNF blocker therapy, similar toxicities may also result from the use of CIMZIA^® in these combinations. Therefore, the combination of CIMZIA^® with anakinra, abatacept, rituximab, or natalizumab is not recommended. Interference with certain coagulation assays has been detected in patients treated with CIMZIA^®. There is no evidence that CIMZIA^® therapy has an effect on in vivo coagulation. CIMZIA^® may cause erroneously elevated aPTT assay results in patients without coagulation abnormalities.

Autoimmunity

Treatment with CIMZIA^® may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. Discontinue treatment if symptoms of lupus-like syndrome develop.

Immunizations

Do not administer live vaccines or live-attenuated vaccines concurrently with CIMZIA^®.

Adverse Reactions

In controlled Crohn's clinical trials, the most common adverse events that occurred in ≥5% of CIMZIA^® patients (n=620) and more frequently than with placebo (n=614) were upper respiratory infection (20% CIMZIA^®, 13% placebo), urinary tract infection (7% CIMZIA^®, 6% placebo), and arthralgia (6% CIMZIA^®, 4% placebo). The proportion of patients who discontinued treatment due to adverse reactions in the controlled clinical studies was 8% for CIMZIA^® and 7% for placebo.

In controlled RA clinical trials, the most common adverse events that occurred in ≥3% of patients taking CIMZIA^® 200 mg every other week with concomitant methotrexate (n=640) and more frequently than with placebo with concomitant methotrexate (n=324) were upper respiratory tract infection (6% CIMZIA^®, 2% placebo), headache (5% CIMZIA^®, 4% placebo), hypertension (5% CIMZIA^®, 2% placebo), nasopharyngitis (5% CIMZIA^®, 1% placebo), back pain (4% CIMZIA^®, 1% placebo), pyrexia (3% CIMZIA^®, 2% placebo), pharyngitis (3% CIMZIA^®, 1% placebo), rash (3% CIMZIA^®, 1% placebo), acute bronchitis (3% CIMZIA^®, 1% placebo), fatigue (3% CIMZIA^®, 2% placebo). Hypertensive adverse reactions were observed more frequently in patients receiving CIMZIA^® than in controls. These adverse reactions occurred more frequently among patients with a baseline history of hypertension and among patients receiving concomitant corticosteroids and non-steroidal anti-inflammatory drugs. Patients receiving CIMZIA^® 400 mg as monotherapy every 4 weeks in RA controlled clinical trials had similar adverse reactions to those patients receiving CIMZIA^® 200 mg every other week. The proportion of patients who discontinued treatment due to adverse reactions in the controlled clinical studies was 5% for CIMZIA^® and 2.5% for placebo.

The safety profile for patients with Psoriatic Arthritis (PsA) treated with CIMZIA^® was similar to the safety profile seen in patients with RA and previous experience with CIMZIA^®.

The safety profile for AS patients treated with CIMZIA^® was similar to the safety profile seen in patients with RA.

For full prescribing information, please visit www.ucb.com

References

1. Sandborn WJ, Lee SD, Randall C, et. al. Long-term safety and efficacy of certolizumab pegol in the treatment of Crohn's disease: 7-year results from the PRECiSE 3 study. Aliment Pharmacol Ther. 2014;40(8):903-916.  
2. Sandborn WJ, Feagan BG, Stoinov S,et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007;357:228-38.
3. Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007;357:239-250.
4. Data on file. UCB, Inc; Smyrna, GA, 2010.
5. Lichtenstein GR, Thomsen OO, Schreiber S, et al. Clin Gastroenterol Hepatol. 2010;8(7):600-609.
6. Vermeire S, Schreiber S, Sandborn WJ, Dubois C, Rutgeerts P. Clin Gastroenterol Hepatol. 2010;8(4):357-363.
7. Harvey RF, Bradshaw JM. Lancet. 1980;1(8167):514.
8. What is Crohn's Disease? Crohn's & Colitis Foundation of America. Accessed 16th March 2015 from http://www.ccfa.org/what-are-crohns-and-colitis/what-is-crohns-disease/  
9. CIMZIA^® U.S. Prescribing Information. Accessed 16th March 2015 from http://www.ucb.com/_up/ucb_com_products/documents/Cimzia_COL_10_2013.pdf   

CIMZIA^® is a registered trademark of the UCB Group of Companies.

For further information

• Andrea Levin Christopher, Communications Lead, Immunology, UCB, Inc.
  T +1 770 970 8352, [email protected]

About UCB
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 8500 people in approximately 40 countries, the company generated revenue of € 3.3 billion in 2014. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news

Forward looking statements- UCB
This press release contains forward-looking statements based on current plans, estimates and beliefs of management. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, political, regulatory or clinical results and other such estimates and results. By their nature, such forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions which could cause actual results to differ materially from those that may be implied by such forward-looking statements contained in this press release.

Important factors that could result in such differences include: changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, product liability claims, challenges to patent protection for products or product candidates, changes in laws or regulations, exchange rate fluctuations,  changes or uncertainties in tax laws or the administration of such laws and hiring and retention of its employees. UCB is providing this information as of the date of this press release and expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report a change in its expectations.

There is no guarantee that new product candidates in the pipeline will progress to product approval or that new indications for existing products will be developed and approved. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences between the partners. Also, UCB or others could discover safety, side effects or manufacturing problems with its products after they are marketed.

Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement.

SOURCE UCB

Related Links

http://www.ucb.com