Basel, 23 March 2012
Roche's Herceptin given by subcutaneous injection
offers greater convenience to patients and reduces overall
healthcare costs compared to standard IV infusion
Subcutaneous administration of Herceptin is less invasive
and takes approximately 5 minutes instead of 30-90 minutes
with currently approved IV administration
Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results
from the Phase III HannaH study in women with HER2-positive
early breast cancer (eBC) showing for the first time that a
new way of giving Herceptin (trastuzumab) by subcutaneous
(SC) injection leads to comparable efficacy (based on
pathological complete response (pCR); complete eradication
of the tumour cells in the breast) to the current way of
giving the medicine by intravenous (IV) route. Herceptin SC
may provide greater convenience to patients versus the
traditional IV method due to its less invasive
administration route and quicker administration time (5
minutes versus 30 - 90 minutes). The HannaH study also
demonstrated Herceptin SC had comparable mean
concentrations of Herceptin in the blood (pharmacokinetics;
PK) versus the IV formulation. The overall safety profile
in both arms of the HannaH study was consistent with that
expected from treatment with Herceptin and standard
chemotherapy in this setting. The results were presented
today at the 8th European Breast Cancer Conference (EBCC-8)
in Vienna (Abstract # 1BA) as part of the EBCC-8
keynote symposium session.
"The subcutaneous formulation of Herceptin provides an
alternative to intravenous Herceptin and is an important
treatment option for patients with HER2 positive breast
cancer," said Hal Barron, M.D., Chief Medical Officer and
Head, Global Product Development. "Because it is less
invasive and takes 5 rather than 30-90 minutes to
administer, subcutaneous Herceptin is more convenient for
patients and may reduce healthcare costs relative to the
standard intravenous formulation."
The SC administration is a less invasive administration
process than the IV infusion and may allow patients to
spend less time in hospital receiving their Herceptin
treatment compared with the IV method. This is important in
the eBC setting where Herceptin is usually given for 1
year. Herceptin SC is given as an injection under the skin
at a fixed dose of 600 mg. In contrast to IV Herceptin, a
loading dose and weight-adjusted dosing are not required
for the SC formulation and the same dose is used
irrespective of patient's body weight.
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
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).
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.
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)).
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:
Pathologic complete response (pCR).
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.
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.
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.
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 allows the use of both vial
administration and administration via the ready-to-use
device with the option of self-administration.
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.
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
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.
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 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.