Cimzia Total Product Profile

Cimzia Total Product Profile

Product Category & MOA

• Cimzia, is a TNF (tumor necrosis factor) blocker -- the same class of drugs as Enbrel, Remicade, and Humira.

• CIMZIA is composed of the Fab' antigen-binding domain of a humanized anti-TNF antibody, site-specifically bound to PEG so that it does not interfere with TNF binding.1,5 In studies, CIMZIA was shown to bind to and neutralize both membrane-bound and soluble human TNF-alpha in a dose-dependent manner.5

• Because it lacks the Fc portion of the antibody, CIMZIA does not fix complement or induce antibody-dependent cell-mediated cytotoxicity in vitro.5 The clinical relevance of in vitro findings is unknown. CIMZIA also does not induce apoptosis or neutrophil degranulation.

medical need for target disease

• Need & Disease fit

http://www.cdc.gov/arthritis/basics.htm

Safety/Efficacy

• Endpoints; Data from Publications; Other Indications)

• Safety (Data from publications) • Pharmacokinetics / Drug Interactions (Data

from pubs)

RAPID 1 (52-week study) and RAPID 2 (24-week study) evaluated 2 doses of CIMZIA (200 mg and 400 mg) every 2 weeks in combination with weekly methotrexate (MTX) in adult patients with active rheumatoid arthritis (RA) and an incomplete response to MTX alone.1,2 ACR response data for the CIMZIA 200 mg plus MTX treatment group of RAPID 1 are summarized below.

In pivotal studies evaluating CIMZIA for treatment of moderately to severely active rheumatoid arthritis (RA), patients treated with CIMZIA experienced significant improvement in all ACR core measures of disease activity, including reduction in the total number of swollen and tender joint counts.1-3 These improvements were both rapid and sustained.1-

3

In pivotal studies evaluating CIMZIA for treatment of moderately to severely active rheumatoid arthritis (RA), patients treated with CIMZIA experienced significant improvement in all ACR core measures of disease activity, including reduction in the total number of swollen and tender joint counts.1-3 These improvements were both rapid and sustained.1-

3

Joint count data for the CIMZIA 200 mg every 2 weeks plus methotrexate (MTX) treatment group of RAPID 1 (52-week study) and for the CIMZIA 400 mg every 4 weeks group of FAST4WARD (24-week monotherapy study) are summarized below.

• FAST4WARD: Significant, sustained reduction of swollen and tender joints3

• CIMZIA also produced significant improvement in the total number of swollen and tender joints in the FAST4WARD (monotherapy) trial.3 As in RAPID 1, these improvements were seen as early as week 1 and were sustained through week 24 (study conclusion).3

• At week 1, swollen joint counts had decreased by 28% from baseline (vs 14% for placebo), and tender joint counts had decreased 33% (vs 16%)3,4

• At week 12, swollen joint counts had decreased by 54% from baseline (vs 32% placebo), and tender joint counts had decreased 51% (vs 25%)4

• At week 24, swollen joint counts were 55% lower than at baseline (vs 32% for placebo), and tender joint counts had decreased 54% (vs 26%)3,4

• CIMZIA pivotal studies: Patient-reported outcomes (PROs) • One of the secondary objectives of the pivotal studies of CIMZIA was to assess the impact of CIMZIA on

health-related outcomes of importance to patients with active rheumatoid arthritis (RA). 2,4,5 Validated patient self-report instruments were used to assess patient outcomes at baseline and at multiple intervals until study completion or patient withdrawal.1,2,6

• Pain, fatigue, disability, and health-related quality of life. PROs assessed in RAPID 1, RAPID 2, and FAST4WARD included physical function/disability (HAQ-DI), fatigue (FAS), arthritis pain (VAS), and health-related quality of life (SF-36). Published analyses of data from these assessments show that treatment with CIMZIA plus MTX (RAPID 1) and CIMZIA monotherapy (FAST4WARD) resulted in significant improvements in pain, fatigue, and disability as early as week 1.1,2,4

Learn more• Productivity. RAPID 1 and RAPID 2 used the validated RA-specific Work Productivity Survey (WPS-RA) to

assess the impact of CIMZIA plus methotrexate (MTX) on productivity outside and within the home. Published analysis of data from these assessments shows that CIMZIA plus MTX resulted in significant improvement over placebo plus MTX on all assessed measures of productivity.3

Side Effects• What is the most important information I should know about CIMZIA?

CIMZIA is a medicine that affects your immune system. CIMZIA can lower the ability of the immune system to fight infections. Serious infections have happened in patients taking CIMZIA. These infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients have died from these infections.

• Your doctor should test you for TB before starting CIMZIA • Your doctor should monitor you closely for signs and symptoms of TB during treatment with CIMZIA• Certain Types of Cancer

There have been cases of unusual cancers in children and teenage patients using TNF-blocking agents. CIMZIA is not approved for use in pediatric patients. For people taking TNF-blocker medicines, including CIMZIA, the chances for getting lymphoma or other cancers may increase. People with RA, especially more serious RA, may have a higher chance for getting a kind of cancer called lymphoma.

• What are the possible side effects of CIMZIA?CIMZIA can cause serious side effects including:

• Heart Failure including new heart failure or worsening of heart failure you already have• Nervous System Problems such as Multiple Sclerosis, seizures, or inflammation of the nerves of the eyes• Allergic Reactions. Signs of an allergic reaction include a skin rash, swollen face, or trouble breathing• Hepatitis B virus reactivation in patients who carry the virus in their blood. In some cases, patients have died as a result of hepatitis B virus being reactivated. Your doctor

should monitor you carefully during treatment with CIMZIA if you carry the hepatitis B virus in your blood.• Blood Problems. Your body may not make enough of the blood cells that help fight infections or help stop bleeding• Immune reactions including a lupus-like syndrome. Symptoms include shortness of breath, joint pain, or a rash on the cheeks or arms that worsens with sun exposure.• Call your doctor right away if you develop any of the above side effects or symptoms.• The most common side effects of CIMZIA are: upper respiratory infections (flu, cold), rash, and urinary tract infections (bladder infections).• Other side effects have happened in some people including new psoriasis or worsening of psoriasis you already have and injection site reactions.• How should I use CIMZIA?

CIMZIA is available as a lyophilized powder for reconstitution or a prefilled syringe. If your doctor prescribes the lyophilized pack, CIMZIA should be injected by a healthcare provider. If your doctor prescribes the prefilled syringe, see the booklet called "Patient Instructions for Use" packaged in your CIMZIA prefilled syringe kit for complete instructions for use. Do not give yourself an injection of CIMZIA unless you have been shown by your doctor or nurse, or they can train someone you know to help you with your injection. CIMZIA is given by an injection under the skin. Your doctor will tell you how much CIMZIA to inject and how often, based on your condition to be treated. Make sure to keep all of your injection and follow-up appointments with your doctor.

• After starting CIMZIA, if you get an infection, any sign of an infection including a fever, cough, flu-like symptoms, or have open cuts or sores on your body, call your doctor right away. CIMZIA can make you more likely to get infections or make any infection that you may have worse. Patients 65 years of age or older, patients with other long term medical conditions, or taking certain other drugs that affect the immune system, such as corticosteroids or methotrexate, may be at a greater risk of infection.

• What are the possible side effects of CIMZIA? CIMZIA can cause serious side effects including:

• Heart Failure including new heart failure or worsening of heart failure you already have. Symptoms may include shortness of breath or swelling of your ankles or feet.• Nervous System Problems such as Multiple Sclerosis, seizures, or inflammation of the nerves of the eyes. Symptoms include dizziness, numbness or tingling, problems with

your vision, and weakness in your arms or legs.• Allergic Reactions. Signs of an allergic reaction include a skin rash, swollen face, or trouble breathing• Hepatitis B virus reactivation in patients who carry the virus in their blood. In some cases, patients have died as a result of hepatitis B virus being reactivated. Your doctor

should monitor you carefully during treatment with CIMZIA if you carry the hepatitis B virus in your blood. Tell your doctor if you have any of the following symptoms: feel unwell, poor appetite, tiredness (fatigue), fever, skin rash, or joint pain.

• Blood Problems. Your body may not make enough of the blood cells that help fight infections or help stop bleeding. Symptoms include a fever that doesn't go away, bruising or bleeding very easily, or looking very pale.

• Immune reactions including a lupus-like syndrome. Symptoms include shortness of breath, joint pain, or a rash on the cheeks or arms that worsens with sun exposure.

Safety• What is the most important information I should know about CIMZIA?

CIMZIA is a medicine that affects your immune system. CIMZIA can lower the ability of the immune system to fight infections. Serious infections have happened in patients taking CIMZIA, including tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients have died from these infections.

• Your doctor should test you for TB before starting CIMZIA• Your doctor should monitor you closely for signs and symptoms of TB during treatment with CIMZIA.• Certain Types of Cancer

There have been cases of unusual cancers in children and teenage patients using TNF-blocking agents. CIMZIA is not approved for use in pediatric patients. For people taking TNF-blocker medicines, including CIMZIA, the chances for getting lymphoma or other cancers may increase. People with RA, especially more serious RA, may have a higher chance for getting a kind of cancer called lymphoma.

• What is CIMZIA?CIMZIA is a medicine called a tumor necrosis factor (TNF)-blocker. CIMZIA is used in adult patients to:

• Lessen the signs and symptoms of moderately to severely active Crohn's disease (CD) in adults who have not been helped enough by usual treatments• Treat moderately to severely active rheumatoid arthritis (RA)• Before starting CIMZIA, tell your doctor about all of your medical conditions, including if you: • Think you have an infection. You should not start taking CIMZIA if you have any kind of infection.• Are being treated for an infection• Have signs of an infection, such as a fever, cough, flu-like symptoms• Have any open cuts or sores on your body• Get a lot of infections or have infections that keep coming back• Have diabetes• Have HIV• Have TB, or have been in close contact with someone with TB• Were born in, lived in, or traveled to countries where there is more risk of getting TB. Ask your doctor if you are not sure.• Live or lived in certain parts of country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections

(histoplasmosis, coccidioidomycosis, blastomycosis). These infections may develop or become severe if you take CIMZIA. If you do not know if you have lived in these types of areas, ask your doctor.

• Have or have had hepatitis B• Have or have had any type of cancer • Have congestive heart failure• Have seizures, any numbness or tingling, or a disease that affects your nervous system such as multiple sclerosis• Are scheduled to receive a vaccine. Do not receive a live vaccine while taking CIMZIA• Are pregnant, planning to become pregnant, or breastfeeding. CIMZIA has not been studied in pregnant or nursing women.• Are allergic to any of the ingredients in CIMZIA.• Are taking any medicines, including prescription and nonprescription medicines, vitamins and herbal supplements. Your doctor will tell you if it is okay to take your other

medicines while taking CIMZIA.• Especially tell your doctor if you take: Kineret® (anakinra), Orencia® (abatacept), Rituxan® (rituximab), Tysabri® (natalizumab). You have a higher chance for serious infections when

taking CIMZIA with these medicines.• A TNF blocker Remicade® (infliximab), Humira® (adalimumab), Enbrel® (etanercept), or Simponi® (golimumab). • You should not take CIMZIA while you take one of these medicines.

Safety

Incidence taken from cancer registries. Excludes nonmelanoma skin cancer cases and cancers occurring within 30 days of first injection of study drug.During controlled and open-label portions of CIMZIA studies of Crohn's disease and other diseases, malignancies were observed at a rate (95% confidence interval) of 0.5 (0.4, 0.7) per 100 patient-years among 4650 CIMZIA-treated patients versus a rate of 0.6 (0.1, 1.7) per 100 patient-years among 1319 placebo-treated patients.2 In CIMZIA RA clinical trials, (placebo-controlled and open label), a total of 3 cases of lymphoma were observed among 2367 patients.

Formulation

PEGylation provides a protective barrier around part of the medicine

Unique properties of PEGylated proteinsPEG has several beneficial properties that transfer to the compounds to which it is covalently bound.1,2 PEG is highly water soluble as well as flexible and stable in solution.1,2 It also tightly binds to water molecules, resulting in increased hydrodynamic volume.1,2

As a result of PEGylation, a therapeutic protein becomes highly hydrated and mobile in solution and much larger than the parent protein,3 with the following advantages:Prolonged circulation time due to protection against enzymatic degradation and slower renal filtration (decreased drug clearance)2

Improved stability over a range of pH and temperature changes3

Dose / Schedule / Formulation• CIMZIA comes in 2 forms. One is a powder that is

mixed with sterile water by the physician or nurse just before being injected. This form can be given only by a doctor or nurse. The other form is the CIMZIA prefilled syringe, which is already mixed and ready to inject. The patient or a caretaker can give the shot using the CIMZIA prefilled syringe.

• Each prefilled syringe contains the right dose of medicine for one injection (200 mg).

Addressable Market: RABased on 2007-2009 data from the National Health Interview Survey (NHIS)(1), an estimated50 million (22%) of adults have self-reported doctor-diagnosed arthritis.21 million (9% of all adults) have arthritis and arthritis-attributable activity limitation. Based on 2003 NHIS data (2) a projected67 million (25%) adults aged 18 years and older will have doctor-diagnosed arthritis by the year 2030.An estimated 25 million adults (37%) of those with arthritis will report arthritis-attributable activity limitations. A newly published CDC study found that from 1997 to 2005, total expenditures among U.S. adults with arthritis increased by 22% from $252 billion in 1997 to $353 billion in 2005. Medical expenditures increased because the number of people with arthritis increased by 22% and medical expenditures for each person with arthritis increased by 15%. Prescription drug costs accounted for the biggest portion of this increase. Costs for ambulatory care also increased while hospital care costs decreased.Medical expenditures among people with arthritis are likely to continue rising as another recent CDC study projected that the number of people with arthritis would rise by 40% from 2005 to 2030.

Addressable Market: IBD• IBD is one of the five most prevalent gastrointestinal disease burdens in the

United States, with an overall health care cost of more than $1.7 billion. This chronic condition is without a medical cure and commonly requires a lifetime of care. Each year in the United States, IBD accounts for more than 700,000 physician visits, 100,000 hospitalizations, and disability in 119,000 patients. Over the long term, up to 75% of patients with Crohn’s disease and 25% of those with ulcerative colitis will require surgery.3

• Although the incidence and prevalence of ulcerative colitis and Crohn's disease are beginning to stabilize in high-incidence areas such as northern Europe and North America, they continue to rise in low-incidence areas such as southern Europe, Asia, and much of the developing world. As many as 1.4 million persons in the United States and 2.2 million persons in Europe suffer from these diseases. Previously noted racial and ethnic differences seem to be narrowing.

• Recent trends indicate a change in the epidemiology of IBD with previously low incidence areas now reporting a progressive rise in the incidence, while in West European and North American countries the figures have stabilized or slightly increased

Economics / Reimbursement climate

Cimzia, UCB's rheumatoid arthritis treatment. NICE just accepted it--after the company agreed to offer the drug for free during each patient's first 12 weeks of treatment. That's a significant price break. According to The Telegraph, Cimzia will cost £5,005 (roughly $8,000) for the first year's treatment rather than £8,580 (about $13,900). And NICE will start picking up the tab only if patients respond to that first 12 weeks' worth.

Product / Market support

Product / Market support• toll-free number, 1-866-4-CIMZIA, for questions

about rheumatoid arthritis and Crohn’s, including product administration and needle disposal.

Summary Features: Benefits

• Designed specifically for end market users

Summary Features: Limits

Advertising Message• Novelty & Competitive Advantage• Cimzia is the only drug in the TNF class that touts

being less poisonous to cells because of its chemical properties. In addition, compared to other TNF blockers, Cimzia reportedly has a higher affinity for human TNF.

• Flexible dosing schedule 2 or 4 wk• “First-In-Class” vs “Best-In-Class

http://www.healthline.com/health-blogs/healthline-connects/ucbs-cimzia-approved-crohns-disease

CIMZIA is the only PEGylated anti-TNFThere has been increasing interest in the use of antibodies and antibody fragments as the basis for new therapies to combat chronic disease.

Expanded Applications

• Excess TNF-alpha production by the body has been linked to several diseases and conditions

competition• According to a press release dated September 2010, Johnson & Johnson

filed a supplemental BLA (sBLA) to the FDA to expand Simponi’s rheumatoid arthritis label to include the following (www.investor.jnj.com):

• inhibiting the progression of structural damage• inducing major clinical response• maintenance of reducing signs and symptoms and improving physical

function.• This is a necessary step in Simponi’s lifecycle and will give it an

advantage over Cimzia (certolizumab), the US label of which is currently the same as Simponi’s. Datamonitor assumes a positive outcome, and that the FDA will approve these label changes by September 2011. The resulting label change will not have a dramatically positive impact on Simponi’s sales, but Datamonitor holds the view that it will certainly allow the drug to gain a moderately increased market share from its competitors as a consequence.

Future Directions

• Innovative antibody therapeutic developers can take heart from the example of Fresenius/Trion’s trifunctional antibody Removab (catumaxomab) which, through strong liaison with the European regulatory body, was granted marketing authorization last year for the niche indication of malignant ascites.

• The development of smaller antibody therapeutics brings about discussion of new routes of administration, with Ablynx’s nanobodies and GSK’s (through Domantis’s) domain antibody technology.

• Niche, product cross marketing• New Formulations (oral)

International Penetration• Acquisitions of domestic players with expertise in the autoimmune

therapeutic area represent one strategy by which multinational companies can penetrate the highly genericized Indian autoimmune market. This will enable companies to leverage established sales forces and existing relationships with key prescribers. Prospective and existing players also stand to benefit from forging links with the Indian government and health organizations in order to deliver disease awareness and patient education campaigns with a view to improving the presentation and diagnosis of autoimmune conditions.

• Datamonitor forecasts that prevalent autoimmune cases (which include rheumatoid arthritis, psoriasis, and inflammatory bowel disease) will grow from 12 million cases in 2010 to 14 million cases in 2020, providing a large market opportunity for multinational companies looking to establish a presence in the Indian autoimmune market.

Key Points

• Impact: Growing Treatment Need– Rheumatoid Arthritis– IBD

• Novelty– Stability– Efficacy

• Ease of Use• Delivery

– Consumer– Health Care Providers– International Partnerships

References