Media Release
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`Basel, 23March 2012
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`Roche's Herceptin given by subcutaneous injection offers greater convenience to
`patients and reduces overall healthcare costs compared to standard IV infusion
`Subcutaneous administration ofHerceptin is less invasive and takes approximately 5 minutes instead of
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`30-90 minutes with currently approved IV administration
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`Roche {SIX: RO, ROG; OTCQX: RHHBY) today announced results from the Phase III HannaH study in
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`women with HER2-positive early breast cancer { eBC) showing for the first time that a new way of giving
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`Herceptin {trastuzumab) by subcutaneous {SC) injection leads to comparable efficacy (based on pathological
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`complete response (pCR); complete eradication of the tumour cells in the breast) to the current way of giving
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`the medicine by intravenous (IV) route. Herceptin SC may provide greater convenience to patients versus the
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`traditional IV method due to its less invasive administration route and quicker administration time {5
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`minutes versus 30 - 90 minutes). The HannaH study also demonstrated Herceptin SChad comparable mean
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`concentrations of Herceptin in the blood (pharmacokinetics; PK) versus the IV formulation. Th e overall
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`safety profile in both arms of the HannaH study was consistent with that expected from treatment with
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`Herceptin and standard chemotherapy in this setting. The results were presented today at the 8th European
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`Breast Cancer Conference (EBCC-8) in Vienna (Abstract # 1BA) as part of the EBCC-8 keynote symposium
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`session.
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`"The subcutaneous formulation of Herceptin provides an alternative to intravenous Herceptin and is an
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`important treatment option for patients with HER2 positive breast cancer," said Hal Barron, M.D., Chief
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`Medical Officer and Head, Global Product Development. "Because it is less invasive and takes 5 rather th an
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`30-90 minutes to administer, subcutaneous Herceptin is more convenient for patients and may reduce
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`healthcare costs relative to the standard intravenous formulation."
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`The SC administration is a less invasive administration process than the IV infusion and may allow patients
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`to spend less time in hospital receiving their Herceptin treatment compared with the IV method. Th is is
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`important in the eBC setting where Herceptin is usually given for 1 year. Herceptin SC is given as an
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`injection under the skin at a fixed dose of 600 mg. In contrast to IV Herceptin, a loading dose and weight(cid:173)
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`adjusted dosing are not required for the SC form ulation and the same dose is used irrespective of patient's
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`F. Hoffmann-La Roche Ltd
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`4070 Basel
`Switzerland
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`Group Communications
`Roche Group Media Relations
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`TeL +41 61 688 88 88
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`www.roche.com
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`CSL EXHIBIT 1056
`CSL v. Shire
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`body weight.
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`Based on the HannaH data, Roche has submitted a Line Extension Application for Herceptin SC to the
`European Medicines Agency (EMA), for the treatment of HER2-positive breast cancer.
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`The co-primary endpoints of PK and efficacy met their pre-specified criteria. The drug concentration in the
`blood measured just before surgery was at least as high for the SC as for the IV formulation (69.0 and 51.8
`μg/mL, respectively). This is important in order to demonstrate comparable efficacy. In addition, efficacy,
`determined by pCR, in patients treated in the SC arm was in the same range as in patients who received the
`IV formulation (45.4 percent and 40.7 percent, respectively).
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`All-grade adverse events (AEs) and severe AEs were comparable between arms. The most frequent AEs in
`either arm (above 25% in either arm) were alopecia, nausea, neutropenia, diarrhoea, asthenia and fatigue.
`More adverse events were reported as serious in the SC arm but no specific clinical explanation (e.g. from
`underlying patient or drug characteristics) for this finding was detected.
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`About subcutaneous delivery
`Herceptin SC is a new more convenient formulation of Herceptin that uses Enhanze™ Technology, developed
`by Halozyme Therapeutics, Inc. which contains the novel excipient (carrier for active ingredients of a
`medication), rHuPH20. rHuPH20 (recombinant human hyaluronidase) reversibly breaks down a gel-like
`substance (hyaluronan) that forms a barrier in the tissues between cells under the skin. This facilitates the
`distribution of injected volumes over a greater area and enables painless subcutaneous administration of the
`large volume of Herceptin SC (a fixed dose of 600 mg (5ml)).
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`About the HannaH study
`HannaH is a Phase III, randomised, open-label, international, multicentre study. A total of 596 patients with
`operable or locally advanced eBC were enrolled. The study investigated the efficacy, pharmacokinetics and
`safety of Herceptin SC (in a ready-to-use vial) and Herceptin IV in the neoadjuvant–adjuvant treatment
`setting (given before and after surgical intervention) of women with HER2-positive eBC. Treatment duration
`was 1 year in total for both arms.
`The co-primary endpoints were:
`• Pharmacokinetics (PK).
`• Pathologic complete response (pCR).
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`Main secondary endpoints were:
`• Safety and tolerability
`• pCR in the breast and axilla (tpCR).
`• Event free survival (EFS) and overall survival (OS).
`Participants in the Herceptin SC arm received:
`• 600 mg (fixed dose) of Herceptin SC plus chemotherapy for 8 cycles before surgery.
`• Herceptin SC alone for 10 cycles after surgery.
`Participants in the Herceptin IV arm received:
`• An initial 8 mg/kg body weight loading dose of Herceptin IV followed by 6 mg/kg maintenance dose
`both in combination with chemotherapy for a total of 8 cycles before surgery, as per the standard IV
`regimen.
`• Herceptin IV alone for 10 cycles after surgery.
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`Adverse Events (AEs) in the study were consistent with the known Herceptin safety profile. No new safety
`signals were identified. Overall, the incidence of most common AEs (above 10% in either arm) was
`comparable. Severe AEs (grade >3) occurred at a similar incidence between arms (52 percent for Herceptin
`IV and 51.9 percent for Herceptin SC). Cardiac adverse events were similar in both treatment arms: 12.1
`percent vs. 11.4 percent in the IV and SC arms respectively. 11 percent of patients who received the SC
`injection experienced an injection site reaction (most commonly pain at the site of injection) which was mild
`in intensity in 95 percent of patients.
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`Clinical trials – SC
`Two additional Herceptin SC studies are currently ongoing. PrefHer is a randomised, multi-centre,
`multinational cross-over study to evaluate patient preference and healthcare professional satisfaction with SC
`administration of Herceptin as an adjuvant therapy in patients with HER2-positive eBC. PrefHer is a two
`cohort study (involving 400 patients in total) comparing Herceptin SC administration, via vial or an
`innovative ready-to-use device, with Herceptin IV administration. The ready-to-use injection device is an
`important advance as it could eventually allow patients to self-administer Herceptin. Data is expected in
`2013.
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`SafeHer is a two-cohort multinational and open label study to assess the safety of assisted- and self-
`administered SC Herceptin as an adjuvant therapy in patients with operable HER2-positive eBC. The study
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`allows the use of both vial administration and administration via the ready-to-use device with the option of
`self-administration.
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`Roche are also investigating the use of MabThera (rituximab) for subcutaneous injection in non-Hodgkin’s
`lymphoma and chronic lymphocytic leukaemia. MabThera for subcutaneous injection is not currently
`licensed or approved in any market. Roche anticipates an initial EU filing in late 2012.
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`About breast cancer
`Breast cancer is the most common cancer among women worldwide.1 Each year about 1.4 million new cases
`of breast cancer are diagnosed worldwide, and over 450,000 women will die of the disease annually.1 In
`HER2-positive breast cancer, increased quantities of the human epidermal growth factor receptor 2 (HER2)
`are present on the surface of the tumour cells. This is known as “HER2 positivity” and affects approximately
`15-20 percent of women with breast cancer.2 HER2-positive cancer is a particularly aggressive form of breast
`cancer.3
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`About Herceptin
`Herceptin (trastuzumab) is a humanised monoclonal antibody, designed to target and block the function of
`HER2, a protein produced by a specific gene with cancer-causing potential when it is overexpressed. The
`mode of action of Herceptin is unique in that it activates the body’s immune system and suppresses HER2
`signalling to target and destroy the tumour. Herceptin has demonstrated unprecedented efficacy in treating
`both early and advanced (metastatic) HER2-positive breast cancer. Given on its own as monotherapy as well
`as in combination with or following standard chemotherapy, Herceptin has been shown to improve overall
`survival, response rates and disease-free survival while maintaining quality of life in women with HER2-
`positive breast cancer. Herceptin is marketed in the United States by Genentech, in Japan by Chugai and
`internationally by Roche. Since 1998, Herceptin has been used to treat almost 1 million people with HER2-
`positive breast cancer worldwide.
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`About Roche
`Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined
`strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly
`differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world
`leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s
`personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible
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`improvements in the health, quality of life and survival of patients. In 2010, Roche had over 80’000
`employees worldwide and invested over 9 billion Swiss francs in R&D. The Group posted sales of 47.5 billion
`Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority
`stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.
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`All trademarks used or mentioned in this release are protected by law.
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`Additional information
`Roche in Oncology: www.roche.com/de/media/media backgrounder/media oncology.htm
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`Roche Group Media Relations
`Phone: +41 61 688 8888 / e-mail: basel.mediaoffice@roche.com
`- Alexander Klauser (Head)
`- Silvia Dobry
`- Daniel Grotzky
`- Claudia Schmitt
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`References
`1) Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM GLOBOCAN 2008, Cancer Incidence and Mortality
`Worldwide: IARC Cancer Base No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available
`from: http://globocan.iarc.fr.
`2) Wolff A.C et al. American Society of Clinical Oncology/ College of American Pathologists Guideline Recommendations for
`Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Arch Pathol Lab Med—Vol 131, January 2007.
`3) Slamon D et al. Adjuvant Trastuzumab in HER2-Positive Breast Cancer. N Engl J Med 2011; 365:1273-83.
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