-- Subcutaneous administration is preferred by patients, physicians and 
      healthcare providers, and is associated with a reduction in healthcare 
      costs1,2,3 
 
   -- Treatment with Phesgo is over 90% faster, administered under the skin in 
      just minutes compared to hours with intravenous (IV) infusion of Perjeta 
      plus Herceptin4,5,6 
 
   -- Approval is based on results from the pivotal phase III FeDeriCa trial, 
      which showed that Phesgo delivered non-inferior levels of Perjeta and 
      Herceptin in the blood and comparable efficacy and safety versus IV 
      formulations7 
 
   Basel, 23 December 2020 -- Roche (SIX: RO, ROG; OTCQX: RHHBY) today 
announced that the European Commission has approved Phesgo(R) , a 
fixed-dose combination of Perjeta(R) (pertuzumab) and Herceptin(R) 
(trastuzumab) with hyaluronidase, administered by subcutaneous (SC; 
under the skin) injection for the treatment of early and metastatic 
HER2-positive breast cancer. 
 
 
 
   "This approval represents a significant step forward in the treatment of 
HER2-positive breast cancer," said Levi Garraway, M.D., Ph.D., Roche's 
Chief Medical Officer and Head of Global Product Development. "The 
innovation of Phesgo significantly reduces the time people spend 
receiving standard of care therapy with Perjeta and Herceptin, helping 
to minimise the impact of treatment on their everyday lives. It also 
addresses the increasing demand across healthcare systems for faster and 
more flexible treatment solutions." 
 
 
 
   Phesgo is available as a single-dose vial for SC injection and enables 
over 90% faster treatment than IV administration of standard of care 
therapy with Perjeta and Herceptin. SC administration of Phesgo takes 
approximately eight minutes for the initial loading dose and 
approximately five minutes for each subsequent maintenance dose. This is 
compared to approximately 150 minutes for infusion of a loading dose of 
Perjeta and Herceptin using the standard IV formulations, and between 
60-150 minutes for subsequent maintenance infusions of the two 
medicines.(4,5,6) 
 
 
 
   The approval of Phesgo in Europe is based on results from the pivotal 
phase III FeDeriCa study, which showed that treatment with Phesgo 
produced non-inferior levels of Perjeta and Herceptin in the blood and 
demonstrated comparable efficacy versus IV administration of the two 
medicines. The safety profile of Phesgo with chemotherapy was comparable 
to IV administration of Perjeta plus Herceptin and chemotherapy. No new 
safety signals were identified, including no meaningful difference in 
cardiac toxicity.(7) 
 
   The development of Phesgo highlights Roche's commitment to improving 
patients' experience of cancer treatment, looking beyond efficacy 
outcomes and focusing on more flexible treatment solutions. Phesgo has 
the potential to help minimise pressure on healthcare systems by 
reducing administration time, as well as other costs associated with 
treatment, such as time spent in the infusion chair and drug 
preparation.(8,9) The COVID-19 pandemic has further highlighted the need 
to utilise novel approaches that help to manage healthcare capacity to 
free-up time and resources. 
 
   About the FeDeriCa study(7,10) 
 
   FeDeriCa is an international, multi-centre, two-arm, randomised, 
open-label, pivotal phase III study evaluating the pharmacokinetics, 
efficacy and safety of subcutaneous injection of Phesgo in combination 
with chemotherapy, compared with standard intravenous (IV) infusions of 
Perjeta and Herceptin in combination with chemotherapy, in 500 people 
with HER2-positive early breast cancer treated in the neoadjuvant 
(before surgery) and adjuvant (after surgery) settings. The primary 
endpoint of the study is minimum levels of Perjeta in the blood during a 
given dosing interval (C(trough) ), when compared to IV administration 
of Perjeta. Secondary endpoints include safety; minimum levels of 
Herceptin in the blood during a given dosing interval (C(trough) ); and 
total pathological complete response, meaning there is no tumour tissue 
detectable in the tissue removed at the time of surgery. 
 
 
 
   Data from the FeDeriCa study were presented at the San Antonio Breast 
Cancer Symposium in December 2019. The FeDeriCa study met its primary 
endpoint of non-inferior levels of Perjeta in the blood. The geometric 
mean ratio (GMR; a type of average used when assessing pharmacokinetics) 
for the primary endpoint was 1.22 (90% CI: 1.14 to 1.31), with the lower 
limit of the 90% CI of the GMR=1.14>=0.80 (the pre-specified 
non-inferiority margin). A secondary endpoint of non-inferior levels of 
Herceptin was also met, with blood concentrations for people receiving 
Phesgo non-inferior to those receiving IV Herceptin (GMR=1.33 [90% CI: 
1.24 to 1.43]; lower limit of 90% CI of GMR=1.24>=0.80). A 
non-inferiority endpoint was chosen for the study to ensure that people 
were receiving sufficient dosing with Perjeta and Herceptin as compared 
to the established IV doses at the same treatment intervals. 
 
   About Phesgo 
 
   Phesgo combines the same monoclonal antibodies as Perjeta and Herceptin 
with Halozyme Therapeutics' Enhanze(R) drug delivery technology in a 
novel formulation for subcutaneous (SC) use.(4,11) This is the first 
time that Roche has combined two monoclonal antibodies that can be 
administered by a single SC injection. 
 
 
 
   Halozyme's Enhanze drug delivery technology may enable and optimise SC 
drug delivery for appropriate co-administered therapeutics. The 
technology is based on a proprietary recombinant human hyaluronidase 
PH20 (rHuPH20), an enzyme that temporarily degrades hyaluronan -- a 
glycosaminoglycan or chain of natural sugars in the body -- to aid in 
the dispersion and absorption of other injected therapeutic drugs.(11) 
 
 
 
   Pertuzumab in Phesgo is the same monoclonal antibody as in intravenous 
(IV) Perjeta, and trastuzumab in Phesgo is the same monoclonal antibody 
as in IV Herceptin. The mechanisms of action of Perjeta and Herceptin 
are believed to complement each other as both bind to the HER2 receptor, 
but in different locations. The combination of Perjeta and Herceptin is 
thought to provide a more comprehensive, dual blockade of the HER 
signalling pathways.(12,13) 
 
 
 
   Phesgo is approved in the US for the treatment of early and metastatic 
HER2-positive breast cancer. The approved indications for Phesgo mirror 
those of Perjeta. 
 
 
 
   The standard IV formulation of Perjeta in combination with IV Herceptin 
and chemotherapy (the Perjeta-based regimen) is approved in more than 
100 countries for the treatment of both early and metastatic 
HER2-positive breast cancer. In the neoadjuvant (before surgery) early 
breast cancer (eBC) setting, the Perjeta-based regimen has been shown to 
almost double the rate of pathological complete response compared to 
Herceptin and chemotherapy.(14) Additionally, the combination has been 
shown to significantly reduce the risk of recurrence of invasive disease 
or death in the adjuvant (after surgery) eBC setting.(15) In the 
metastatic setting, the combination has shown an unprecedented survival 
benefit in previously untreated (first-line) patients with HER2-positive 
metastatic breast cancer.(16) 
 
 
 
 
 
   About Roche's medicines for HER2-positive breast cancer 
 
   Roche has been leading research into the HER2 pathway for more than 30 
years and is committed to improving the health, quality of life and 
survival of people with both early and metastatic HER2-positive disease. 
HER2-positive breast cancer is a particularly aggressive form of the 
disease that affects approximately 25-30% of patients.(17) Roche has 
developed three innovative medicines that have helped transform the 
treatment of HER2-positive breast cancer: Herceptin, Perjeta and 
Kadcyla(R) (trastuzumab emtansine). Eligibility for treatment with 
Roche's HER2-targeted medicines is determined via a diagnostic test 
which identifies people who will likely benefit from these medicines at 
the onset of their disease. 
 
 
 
   About Roche 
 
   Roche is a global pioneer in pharmaceuticals and diagnostics focused on 
advancing science to improve people's lives. The combined strengths of 
pharmaceuticals and diagnostics under one roof have made Roche the 
leader in personalised healthcare -- a strategy that aims to fit the 
right treatment to each patient in the best way possible. 
 
 
 
   Roche is the world's largest biotech company, with truly differentiated 
medicines in oncology, immunology, infectious diseases, ophthalmology 
and diseases of the central nervous system. Roche is also the world 
leader in in vitro diagnostics and tissue-based cancer diagnostics, and 
a frontrunner in diabetes management. 
 
 
 
   Founded in 1896, Roche continues to search for better ways to prevent, 
diagnose and treat diseases and make a sustainable contribution to 
society. The company also aims to improve patient access to medical 
innovations by working with all relevant stakeholders. More than thirty 
medicines developed by Roche are included in the World Health 
Organization Model Lists of Essential Medicines, among them life-saving 
antibiotics, antimalarials and cancer medicines. Moreover, for the 
twelfth consecutive year, Roche has been recognised as one of the most 
sustainable companies in the Pharmaceuticals Industry by the Dow Jones 
Sustainability Indices (DJSI). 
 
 
 
   The Roche Group, headquartered in Basel, Switzerland, is active in over 
100 countries and in 2019 employed about 98,000 people worldwide. In 
2019, Roche invested CHF 11.7 billion in R&D and posted sales of CHF 
61.5 billion. Genentech, in the United States, is a wholly owned member 
of the Roche Group. Roche is the majority shareholder in Chugai 
Pharmaceutical, Japan. For more information, please visit 
https://www.globenewswire.com/Tracker?data=-JLHvy1j3GpoJJi4DUAogAV7lVKT074Rgltg0lQaVm9emAyDjYhZQdqdPXCkHm-gmo8Wmcx_JFIbKeEMxg2x2Q== 
www.roche.com. 
 
 
 
   All trademarks used or mentioned in this release are protected by law. 
 
 
 
   References

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December 23, 2020 01:00 ET (06:00 GMT)