Hospira Shares Results From Randomised Trials Showing Biosimilar Monoclonal Antibody, Inflectra™, Demonstrates Comparable Reductions in Disease Activity to Remicade® Over One Year

- Evidence base for Inflectra (infliximab) expands as secondary endpoints from randomised, active comparator studies demonstrate comparable reductions in disease activity to Remicade (infliximab) in rheumatoid arthritis and ankylosing spondylitis.

HURLEY, England, June 13, 2014 /PRNewswire/ -- Hospira (NYSE: HSP), the world's leading provider of injectable drugs and infusion technologies, shared data this week showing that the company's biosimilar monoclonal antibody Inflectra^TM demonstrated comparable and sustained reductions in disease activity to European reference product Remicade^® over one year in patients with rheumatoid arthritis and ankylosing spondylitis. The results, shared at the European League Against Rheumatism (EULAR) congress, added to the body of evidence supporting the use of Inflectra - the first biosimilar monoclonal antibody to be approved in Europe - as an alternative to Remicade.^1,2

The data comprise secondary endpoints of two randomised active-comparator studies, the PLANETRA (Programme evaLuating the Autoimmune disease iNvEstigational drug cT-p13 in RA patients), study in rheumatoid arthritis (RA) and the PLANETAS (Programme evaLuating the Autoimmune disease iNvEstigational drug cT-p13 in AS patients) study in ankylosing spondylitis (AS). In the PLANETRA study of nearly 500 patients, Inflectra was shown to be comparable to Remicade across a range of primary and secondary efficacy endpoints in RA after 54 weeks, including mean decrease in Disease Activity Score 28 (DAS28; -2.4 in both treatment groups), Clinical Disease Activity Index (CDAI; -25.7 with Inflectra and -24.0 with Remicade), and Simplified Disease Activity Index (SDAI; -26.3 with Inflectra and -24.6 with Remicade). The effect of anti-drug antibody was also measured and the degree of change in the ADA positive versus negative populations was observed to be the same in both Inflectra and Remicade treatment group. Overall, no statistical difference in clinical responses was observed between the two treatment groups.¹ Data for these endpoints have been previously reported at week 30.³

In the PLANETAS study of approximately 250 patients, Inflectra was shown to be comparable to Remicade in terms of secondary endpoints reducing disease activity, relieving disability and improving mobility in people with AS after 54 weeks. Overall no statistical difference in clinical responses was observed between the two treatment groups.² Disease activity was measured via the Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20/ASAS40) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The study measured disability via the Bath Ankylosing Spondylitis Functional Index (BASFI) and mobility via the Bath Ankylosing Spondylitis Metrology Index (BASMI).² Data for these endpoints have been previously reported at week 30.³

Overall, the type and incidence of adverse events reported with Inflectra and Remicade in the RA and AS trials appeared generally similar to the type and incidence of adverse events reported in the European product label for Remicade.

"The additional data on reduction in disease activity from the PLANETRA and PLANETAS studies provide further evidence that Inflectra can deliver the treatment benefits of Remicade at a reduced cost to healthcare systems," said Paul Audhya, M.D., Vice President, Medical Affairs, Hospira. "This is exciting, as we are truly seeing the potential of biosimilars to make complex biologic treatments ever more accessible to the people who need them."

Biologic treatments are important therapeutic options for RA and AS but can be very expensive, and studies have shown that this can limit patient access and lead to inequalities developing across Europe.⁴ Licensed biosimilars offer a considerable opportunity to reduce healthcare spending by offering clinicians an alternative, more affordable treatment option, while maintaining the same quality, efficacy and safety of treatment. Biosimilar monoclonal antibodies are expected to deliver cost savings of between €1.8-20.4 billion across Europe by 2020.⁵

The primary endpoints from the PLANETRA and PLANETAS studies have been reported previously. PLANETRA met its primary endpoint of therapeutic equivalence between Inflectra and Remicade as measured by ACR20* at week 30 (3mg/kg both arms).¹ PLANETAS was principally a pharmacokinetics study and met its primary endpoint of demonstrating similar bioavailability between Inflectra and Remicade (5mg/kg both arms) as measured by maximum serum concentration at steady state and area under the concentration-time curve over a dosing interval of both drugs between Weeks 22 and 30.²

Inflectra is a biosimilar version of the anti-TNFα blockbuster Remicade, and is the first monoclonal antibody to be approved through the European Medicines Agency biosimilars regulatory pathway. Inflectra was approved by the European Commission on 10^th September 2013 for the treatment of rheumatoid arthritis, psoriatic arthritis, Crohn's disease, ulcerative colitis, plaque psoriasis and ankylosing spondylitis.

Hospira has many years of experience in the development, manufacturing, distribution and commercialisation of biologic medicines, and has one of the largest biosimilar pipelines in the industry. It is the only North American-based company with biosimilars on the European market, including Retacrit™ (epoetin zeta) which was launched in Europe in early 2008 and Nivestim™(filgrastim), which entered the European market in 2010 and the Australian market in 2011. Inflectra received European approval in 2013 and is being introduced in select European markets.

View the results of the two studies at the following links:

https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=196212

https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=196038

Three other studies on CT-P13 were also presented at EULAR. They are available at the following links:

https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=195681

https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=195613

https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=194947

About Inflectra
Inflectra (infliximab) is a chimeric human‑murine monoclonal antibody that binds with high affinity to both soluble and transmembrane forms of TNFα but not to lymphotoxin α (TNFβ). Inflectra is indicated for:

Rheumatoid arthritis
Inflectra, in combination with methotrexate, is indicated for the reduction of signs and symptoms as well as the improvement in physical function in:

• Adult patients with active disease when the response to disease‑modifying antirheumatic drugs (DMARDs), including methotrexate, has been inadequate.
• Adult patients with severe, active and progressive disease not previously treated with methotrexate or other DMARDs.

In these patient populations, a reduction in the rate of the progression of joint damage, as measured by X‑ray, has been demonstrated.

Adult Crohn's disease
Inflectra is indicated for:

• Treatment of moderately to severely active Crohn's disease, in adult patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.
• Treatment of fistulising, active Crohn's disease, in adult patients who have not responded despite a full and adequate course of therapy with conventional treatment (including antibiotics, drainage and immunosuppressive therapy).

Paediatric Crohn's disease
Inflectra is indicated for treatment of severe, active Crohn's disease in children and adolescents aged 6 to 17 years, who have not responded to conventional therapy including a corticosteroid, an immunomodulator and primary nutrition therapy; or who are intolerant to or have contraindications for such therapies. Infliximab has been studied only in combination with conventional immunosuppressive therapy.

Ulcerative colitis
Inflectra is indicated for treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6‑mercaptopurine (6‑MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.

Paediatric ulcerative colitis
Inflectra is indicated for treatment of severely active ulcerative colitis in children and adolescents aged 6 to 17 years, who have had an inadequate response to conventional therapy including corticosteroids and 6‑MP or AZA, or who are intolerant to or have medical contraindications for such therapies.

Ankylosing spondylitis
Inflectra is indicated for treatment of severe, active ankylosing spondylitis, in adult patients who have responded inadequately to conventional therapy.

Psoriatic arthritis
Inflectra is indicated for treatment of active and progressive psoriatic arthritis in adult patients when the response to previous DMARD therapy has been inadequate.

Inflectra should be administered:

• In combination with methotrexate
• Or alone in patients who show intolerance to methotrexate or for whom methotrexate is contraindicated.

Infliximab has been shown to improve physical function in patients with psoriatic arthritis, and to reduce the rate of progression of peripheral joint damage as measured by X‑ray in patients with polyarticular symmetrical subtypes of the disease.

Psoriasis
Inflectra is indicated for treatment of moderate to severe plaque psoriasis in adult patients who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or psoralen ultra-violet A (PUVA).

Important Safety Information
There are reports of serious infections, including tuberculosis (TB), sepsis and pneumonia, in patients taking INFLECTRA. Some of these infections have been fatal. Patients should tell their doctors if they have had recent or past exposure to people with TB. Their doctors will evaluate them for TB and may perform tests for TB. If patients have latent (inactive) TB, their doctors should begin TB treatment before they start INFLECTRA. INFLECTRA can lower patients' ability to fight infections, so if they are prone to or have a history of infections, or develop any signs of an infection such as fever, fatigue, cough, flu-like symptoms or warm, red or painful skin while taking INFLECTRA, patients should tell their doctors right away. Also, patients should tell their doctors if they are scheduled to receive a vaccine or if they have lived in a region where histoplasmosis, blastomycosis or coccidioidomycosis are common.

Reports of a type of blood cancer called lymphoma in patients on INFLECTRA or other TNF blockers are rare, but occur more often than expected for people in general. People who have been treated for rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, or psoriatic arthritis for a long time, particularly those with highly active disease may be more prone to develop lymphoma. Cancers, other than lymphoma, have also been reported. Rarely, children and young adults who have been treated for Crohn's disease or ulcerative colitis with INFLECTRA in combination with azathioprine or 6-mercaptopurine have developed a rare type of lymphoma, hepatosplenic T cell lymphoma (HSTCL) that often results in death. Patients taking INFLECTRA or other TNF blockers may be at an increased risk for developing lymphoma or other cancers. Patients should also tell their doctors if they have had or develop lymphoma or other cancers or if they have a lung disease called chronic obstructive pulmonary disease (COPD).

Many people with heart failure should not take INFLECTRA; so prior to treatment they should discuss any heart condition with their doctors. Patients should tell their doctors right away if they develop new or worsening symptoms of heart failure (such as shortness of breath, swelling of ankles or feet, or sudden weight gain).

Reactivation of hepatitis B virus has been reported in patients who are carriers of this virus and are taking TNF blockers, such as INFLECTRA. Some of these cases have been fatal. All patients should be screened for signs of an infection and a hepatitis B expert should be consulted if a patient tests positive for hepatitis B surface antigen.

There have been rare cases of serious liver injury in people taking infliximab, some fatal. Patients should tell their doctors if they have liver problems and contact their doctors immediately if they develop symptoms such as jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe fatigue.

Blood disorders in people taking INFLECTRA have been reported, some fatal. Patients should tell their doctors if they develop possible signs of blood disorders such as persistent fever, bruising, bleeding, or paleness while taking INFLECTRA. Nervous system disorders have also been reported. Patients should tell their doctors if they have or have had a disease that affects the nervous system, or if they experience any numbness, weakness, tingling, visual disturbances or seizures while taking INFLECTRA.

Allergic reactions, some severe have been reported during or after infusions with infliximab. Signs of an allergic reaction include hives, difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, and fever or chills. INFLECTRA should not be administered to patients with known hypersensitivity to INFLECTRA or any component of INFLECTRA. Patients should tell their doctors if they have experienced a severe allergic reaction. The most common side effects of INFLECTRA are: viral infections, headache, upper respiratory-tract infection, sinusitis, nausea, abdominal pain, infusion-related reactions and pain.

See the Summary of Product Characteristics (also part of the EPAR) for full details.

About Hospira
Hospira, Inc. is the world's leading provider of injectable drugs and infusion technologies, and a global leader in biosimilars. Through its broad, integrated portfolio, Hospira is uniquely positioned to Advance Wellness™ by improving patient and caregiver safety while reducing healthcare costs. The company is headquartered in Lake Forest, Ill., and has approximately 17,000 employees. Learn more at www.hospira.com.

The head office for Hospira in Europe, Middle East and Africa is in Hurley, UK.

Private Securities Litigation Reform Act of 1995 –

A Caution Concerning Forward-Looking Statements
This press release contains, or may contain, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding Hospira's biosimilars program and study results related to Inflectra. Hospira cautions that these forward-looking statements are subject to risks and uncertainties, including adequate and sustained progress on the company's quality initiatives and device strategy that may cause actual results to differ materially from those indicated in the forward-looking statements. Economic, competitive, governmental, regulatory, legal, technological, manufacturing, supply, quality, modernizing and streamlining activities, and other factors that may affect Hospira's operations and may cause actual results to be materially different from expectations include the risks, uncertainties and other factors discussed under the headings "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in Hospira's latest Annual Report on Form 10-K and subsequent Forms 10-Q filed with the Securities and Exchange Commission, are incorporated by reference. Hospira undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References
*ACR score is a standard measure of improvement in RA symptoms. An ACR20 score indicates a 20% improvement in defined signs and symptoms of RA. ACR50 and ACR70 scores refer to a 50% and 70% improvement respectively.
¹ Yoo DH et al. Disease activity assessment using the DAS28, CDAI and SDAI and effect of anti-drug antibody on clinical response in a randomised, double-blind, comparative trial of CT-P13 and the innovator infliximab: PLANETRA study. Abstract presented at EULAR 2014. EULAR14-SCIE-3707. Presented June 2014
² Park W et al. Clinical response of disease activity, disability and mobility indices in relation to anti-drug antibody in the PLANETAS. Abstract presented at EULAR 2014. EULAR14-SCIE-3804. Presented June 2014
³ Inflectra. European Public Assessment Report. October 2013.
⁴ Putrik P, Ramiro S, Kvien TK, et al. Inequities in access, to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis 2014 73(1):198-206
⁵ Haustein R. et al. Saving money in the European healthcare systems with biosimilars. Generics and Biosimilars Initiative Journal. 2012;1(3-4):120-6.