病情分析：HR + / HER2-乳腺癌
Disease Analysis: HR+/HER2- Breast Cancer
|出版日期||內容資訊||英文 92 Pages
|病情分析：HR + / HER2-乳腺癌 Disease Analysis: HR+/HER2- Breast Cancer|
|出版日期: 2020年06月19日||內容資訊: 英文 92 Pages|
Datamonitor Healthcare估計，2018年全球乳腺癌患者人數為210萬，五年內為860萬。到2027年，這一數位預計將增長到230萬和930萬。預計在未來十年中，美國，日本和五個歐洲國家（法國，德國，意大利，西班牙和英國）的HER2 +乳腺癌藥物市場將穩定增長。這種增長的主要驅動力是疾病的流行，批准新的靶向療法以及隨後的採用。 HER2 +乳腺癌市場變得越來越擁擠，在已批准的和正在接受的治療之間產生了激烈的競爭。
Human epidermal growth factor 2-positive (HER2+) breast cancer is characterized by amplification of the HER2/neu oncogene. Datamonitor Healthcare estimates that in 2018, there were 2.1 million incident cases and 8.6 million five-year prevalent cases of breast cancer worldwide. By 2027, incident and five-year prevalent cases of breast cancer are expected to increase to 2.3 million and 9.3 million cases, respectively.
The market for drugs for HER2+ breast cancer will experience steady growth over the next 10 years across the US, Japan, and five major European markets (France, Germany, Italy, Spain, and the UK). The primary drivers for this growth are the rising disease prevalence as well as the approval and subsequent uptake of new targeted therapies. The market for HER2+ breast cancer is also becoming increasingly crowded, creating fierce competition among approved and pipeline therapies.
High prices for combination regimens will translate to high revenues, despite the introduction of trastuzumab biosimilars. The increased use of combination regimens, in conjunction with the continued uptake of other branded therapies and rising disease prevalence, will offset the decrease in revenues caused by these biosimilars.
Herceptin is the current standard-of-care therapy, and is used in every line of treatment, primarily as part of a combination regimen. However, it is forecast to steadily lose market share following the introduction of trastuzumab biosimilars in 2019.
Since its approval in 2013, Kadcyla has become the standard of care both for HER2+ breast cancer patients who have residual invasive disease after neoadjuvant taxane- and Herceptin-based treatment, and for patients with metastatic disease who have progressed on a trastuzumab-containing regimen.
Despite initially encountering reimbursement challenges, Perjeta in combination with Herceptin has become the standard of care for both neoadjuvant and first-line treatment of HER2+ breast cancer after demonstrating an overall survival benefit in the Phase III CLEOPATRA and APHINITY studies.
Nerlynx, which is approved for the extended adjuvant setting, has experienced limited commercial success due to a lack of an overall survival benefit, high rates of diarrhea, and high prices. Although Puma Biotechnology is positioning Nerlynx as a third-line treatment, the drug may struggle to gain market share in the increasingly crowded third-line market.
Tykerb's unfavorable clinical results and the success of Kadcyla in later lines of therapy have limited the tyrosine kinase inhibitor's (TKI's) commercial potential. The introduction of Enhertu and other expected third-line treatments will further limit Tykerb's future commercial potential.
Enhertu received accelerated approval in the US as a third-line treatment for locally advanced or metastatic patients after demonstrating strong efficacy results in the pivotal Phase II DESTINY-Breast01 study. Enhertu is currently being tested against investigator's choice of treatment in the confirmatory Phase III DESTINY-Breast02 study. Daiichi Sankyo and AstraZeneca are also testing Enhertu in a head-to-head trial against Kadcyla in the Phase III DESTINY-Breast03 study, which could support a label expansion for Enhertu as a second-line treatment.
Tukysa, which was recently approved in the US, will likely be the treatment of choice in third-line patients with brain metastases after demonstrating positive efficacy results in the pivotal Phase II HER2CLIMB study. However, Tukysa's overall commercial potential will be limited by the small size of the heavily pretreated patient population with brain metastases.
Margetuximab is also under regulatory review for this setting, but has a limited commercial outlook given it will face significant competition from both approved and late-phase competitors in an increasingly crowded market. Although margetuximab demonstrated a progression-free survival benefit and a trend toward an overall survival benefit in the Phase III SOPHIA study, both Tukysa and Enhertu have shown better efficacy results.
The $6.9bn agreement signed in March 2019 between AstraZeneca and Daiichi Sankyo regarding the development and commercialization of Enhertu is the largest deal for a breast cancer therapy.
Key recent events include pivotal trial read-outs, such as Kadcyla's failure as an adjuvant therapy in combination with Perjeta in the Phase III KAITLIN study, as well as Tukysa's Phase II success as a third-line therapy in HER2CLIMB. Key recent regulatory events include the US approval of Tukysa.
Key upcoming catalysts for 2020 include the anticipated US approvals of margetuximab and the Perjeta/Herceptin subcutaneous fixed-dose combination. Additionally, results from the registrational Phase III TULIP study of (vic-)trastuzumab duocarmazine are also expected in 2020.
The overall likelihood of approval of a Phase I breast cancer asset is 8.7%, and the average probability a drug advances from Phase III is 58.8%. Breast cancer drugs, on average, take 9.8 years from Phase I to approval, compared to 9.3 years in the overall oncology space.