PH FDC SC key clinical data: An overview of the data supporting approval and use of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection

[Audio] Good morning today I will be discussing the key clinical data that supports the approval and use of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection which is summarized in the Medical Education Deck of September 2021. This data provides an overview of the information needed to make an informed decision when choosing the appropriate treatment for a patient. We will be looking at efficacy safety pharmacology and more to give us a comprehensive look at this treatment option..

INTRODUCTION.

[Audio] I would like to examine the data that supports the use of a combined fixed-dose of pertuzumab and trastuzumab for subcutaneous injection. This is the initial mAb combination in oncology that is packaged in one vial. The humanized anti-human hyaluronidase antibody rHuPH20 allows higher drug volumes to be administered by SC injection. Before the infusion the patient will receive a bolus injection that consists of 10% IgG solution. Afterwards the patient can use the PH FDC SC which contains the same antibodies as the IV versions of pertuzumab and trastuzumab however with a different route of administration. This ready-to-use PH FDC SC only needs to be injected over 5-8 minutes..

[Audio] The data supporting the approval and use of a fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection is supported by a Phase I-I-I pivotal non-inferiority Pharmacokinetic study named FeDeriCa (WO40324). This study provides important information on the safe and effective use of this combination..

[Audio] FeDeriCA studied the pharmacokinetics efficacy and safety of PHESGO in comparison to the intravenous administration of perjeta and trastuzumab. The outcomes were detailed in the Medical Education Deck published in September 2021 which suggested that PHESGO is an ideal fixed-dose combination of pertuzumab and trastuzumab for subcutaneous administration..

[Audio] Data on this slide presents the outcomes of a pharmacokinetic study that examined the concentrations of pertuzumab and trastuzumab in PHESGO compared to intravenous perjeta and trastuzumab. The results demonstrate that the fixed-dose combination of pertuzumab and trastuzumab in subcutaneous form is authorized for use with positive outcomes..

[Audio] Data for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection indicates that the most frequent adverse reactions affecting more than 15% of patients are diarrhoea fatigue nausea rash infusion-related reactions and fever. Such reactions typically have mild to moderate severity and can be addressed through supportive care..

[Audio] According to a study that was conducted in September 2021 the results of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection when compared to the pertuzumab and trastuzumab intravenous injection were found to be non-inferior in terms of pharmacokinetics efficacy and safety. It was also established that the tumour complete response rate of the FDC SC injection was nearly identical to that of pertuzumab plus trastuzumab IV and consistent with previous studies from trials with pertuzumab plus trastuzumab IV plus chemotherapy. Additionally the safety profile of PH FDC SC was found to be comparable to that of pertuzumab plus trastuzumab IV and no new safety signals were identified..

[Audio] The PHranceSCa trial sought to examine patient preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection. The trial evaluated efficacy safety and quality of life outcomes in 375 Her2-positive metastatic breast cancer patients who were randomized to either SC FDC or the standard IV infusions of both drugs. The results showed that overall patients preferred the SC FDC option. The vast majority of patients in the SC FDC arm selected it as their preferred method of administration and those in this arm had higher quality of life scores than those in the IV arm. Furthermore outcomes were comparable between the two arms in terms of efficacy and safety. This further supports the approval and use of the SC FDC of pertuzumab and trastuzumab..

[Audio] A recent study PHranceSCa evaluated patient preference of PHESGO compared to intravenous perjeta plus trastuzumab and the findings were encouraging. These findings suggest that a fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection may be a promising choice for patients..

[Audio] Based on the data from our Medical Education Deck of September 2021 the evidence strongly indicates that the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection should be approved and used. A review of patient preferences showed that more than 85% chose PHESGO citing shorter time spent in the clinic as the main reason..

[Audio] A study involving 160 patients who received a fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection tested over two cycles of 3 and 6 months revealed the most common adverse reactions experienced by the patients. In the first cycle of treatment 25% of the patients experienced radiation skin injury 15% had injection site reaction 6.3% had diarrhea 7.5% experienced fatigue and 77.5% had hot flushes. In the second cycle of treatment 8.8% of patients experienced radiation skin injury 15% injection site reaction 8.8 % diarrhea 5% fatigue and 72.5% hot flushes. In total 43 cases of radiation skin injury 36 injection site reactions 25 diarrhea 15 fatigue and 140 hot flushes were reported..

[Audio] The data shows that the fixed-dose combination (F-D-C--) of pertuzumab and trastuzumab for subcutaneous injection is the preferred option among patients and healthcare professionals for several reasons. Patients reported that administration was more comfortable and they were more satisfied with this option in comparison with the intravenous (I-V---) administration. There was also no impact on the amount of time they had to talk to their nurse/doctor and they had more than enough time to do so. A survey of 160 patients revealed that 85% preferred the F-D-C while only 14% preferred the IV. Healthcare professionals also reported that the F-D-C option required fewer resources and resulted in marked time savings. Overall the data presented in this study strongly supports the approval and use of the F-D-C of pertuzumab and trastuzumab for subcutaneous injection..

[Audio] Data in this slide provides a comprehensive overview of the practical benefits of the fixed-dose combination of pertuzumab and trastuzumab that is administered via subcutaneous injection. This combination has been approved for use by the F-D-A and evidence-based benefits include lower rates of infusion reactions with higher patient tolerability. Additionally it offers an improved treatment experience with fewer clinic visits making it more convenient and stress-free for those receiving the treatment..

[Audio] The slide shows the advantages of using the fixed-dose combination of pertuzumab and trastuzumab administered subcutaneously instead of intravenously. The maintenance dose would only take 38 minutes to administer compared to 570 minutes which is a reduction of over 14 times. Furthermore for the loading dose the time needed to administer it is 20 minutes versus 270 minutes a reduction of over 13 times. These major time savings would give healthcare providers more time to offer other chemotherapy treatments..

[Audio] Pertuzumab and trastuzumab given together in a fixed dose combination for subcutaneous injection has been approved by both the F-D-A and the E-M-A for use in the same conditions as the intravenous version. These conditions include high-risk Her2-positive locally advanced inflammatory or early-stage breast cancer for neo-adjuvant therapy and for first-line treatment of metastatic breast cancer. The National Comprehensive Cancer Network (N-C-C-N-) Guidelines recommend that the intravenous version be substituted with the subcutaneous version in treatments for Her2-positive early-stage and metastatic breast cancer..

[Audio] The data confirms that the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection is an effective and safe treatment for advanced-stage Her2-positive breast cancer. The treatment requires less invasive administration methods has Cycle 7 trough concentrations on par with IV methods and does not affect the tpCR rate or increase adverse events making it a worthy addition to the treatment arsenal. " Today I'm here to discuss the data supporting the approval and use of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection. We can see that this treatment requires less invasive methods of administration and has Cycle 7 trough concentrations comparable to intravenous methods. Additionally the tpCR rate and adverse event rate are not impacted by body mass index or even when switching formulations. All of this taken together makes this a new and viable option for treating advanced-stage Her2-positive breast cancer..

[Audio] This presentation summarises data in favour of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection. Most patients choose this combination over P plus H IV irrespective of sequencing and patients and healthcare professionals both acknowledge that this choice has no effect on patient–HCP speaking time. The F-D-A and E-M-A have approved this combination for the same indications as P plus H IV and H-C-P-s believe that switching to SC injections would simplify preparation procedures for most patients..

Thank you.