Disease Analysis: HR+/HER2- Breast Cancer

Latest key takeaways

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.

TABLE OF CONTENTS

CONTENTS

OVERVIEW

• Latest key takeaways

DISEASE BACKGROUND

• Definition
• Risk factors
• Symptoms
• Diagnosis
• Determination of HER2 status
• Patient segmentation

TREATMENT

• Referral patterns
• Operable Stage I-III HER2+ breast cancer
• Inoperable Stage III HER2+ breast cancer
• Neoadjuvant/adjuvant therapy regimens
• Treatment guidelines for Stage IV or recurrent HER2+ breast cancer

EPIDEMIOLOGY

• Breast cancer subtypes

MARKETED DRUGS

PIPELINE DRUGS

KEY REGULATORY EVENTS

• Scottish HTA OKs Neratinib For Early-Stage Breast Cancer
• Updated: Multiple Biosimilars To Avastin Have Launched In EU
• Latest EU Filings Include AstraZeneca/Daiichi Sankyo's Enhertu
• Genentech Wins FDA Approval For Phesgo
• Accord Backed In EU For Trastuzumab And Apixaban
• England's NICE Says Yes To Kadcyla In Early Breast Cancer
• Seattle Genetics Wins Early US FDA Approval For Tukysa, Plans Rapid Launch
• Japan Enhertu Nod Another Boost For Daiichi's Oncology Hopes
• Ide-Cel and Enhertu Sponsors Keep Fingers Crossed For EMA Fast-Track
• India's SPARC Keeps Paclitaxel Ambition Burning For Now
• Assessment Aid Speeds FDA Review Of Nerlynx In Third-Line Breast Cancer
• Seattle Genetics' Tucatinib Moves Quickly From BTD To NDA
• Enhertu Earns Second-Fastest Review Time Of 2019
• First Filing, In Japan, For Daiichi's Lead ADC As Others Progress

PROBABILITY OF SUCCESS

LICENSING AND ASSET ACQUISITION DEALS

• Daiichi Sankyo Partners with Syneos Health for Development of Enhertu and Other Cancer Drugs

CLINICAL TRIAL LANDSCAPE

• Sponsors by status
• Sponsors by phase
• Recent events

DRUG ASSESSMENT MODEL

MARKET DYNAMICS

FUTURE TRENDS

• Launches of new targeted therapies and label expansions will drive growth in the HER2+ breast cancer market over the forecast period
• Uptake of combination regimens will drive high revenues
• Pipeline drugs will face strong competition in a saturated market
• Trastuzumab biosimilars will have a minor impact on the overall market

CONSENSUS FORECASTS

RECENT EVENTS AND ANALYST OPINION

• Tukysa for Breast Cancer (May 29, 2020)
• Kadcyla for Breast Cancer (May 13, 2020)
• Onzeald for Breast Cancer (February 27, 2020)
• Leronlimab for Breast Cancer (January 31, 2020)
• Oral Paclitaxel for Breast Cancer (December 13, 2019)
• Phesgo for Breast Cancer (December 12, 2019)
• Enhertu for Breast Cancer (December 11, 2019)
• Tukysa for Breast Cancer (December 11, 2019)
• MCLA-128 for Breast Cancer (October 23, 2019)
• Margetuximab for Breast Cancer (October 22, 2019)
• Tukysa for Breast Cancer (October 21, 2019)
• Verzenio for Breast Cancer (September 28, 2019)

KEY UPCOMING EVENTS

KEY OPINION LEADER INSIGHTS

UNMET NEEDS

BIBLIOGRAPHY

• Prescription information

APPENDIX

LIST OF FIGURES

• Figure 1: Staging of HER2+ breast cancer
• Figure 2: Trends in incident cases of breast cancer, 2018-27
• Figure 3: Overview of pipeline drugs for breast cancer in the US
• Figure 4: Pipeline drugs for breast cancer, by company
• Figure 5: Pipeline drugs for breast cancer, by drug type
• Figure 6: Pipeline drugs for breast cancer, by classification
• Figure 7: Probability of success in the breast cancer pipeline
• Figure 8: Clinical trials in breast cancer
• Figure 9: Top 10 drugs for clinical trials in breast cancer
• Figure 10: Top 10 companies for clinical trials in breast cancer
• Figure 11: Trial locations in breast cancer
• Figure 12: Breast cancer trials status
• Figure 13: Breast cancer trials sponsors, by phase
• Figure 14: Datamonitor Healthcare's drug assessment summary for HER2+ breast cancer
• Figure 15: Market dynamics for HER2+ breast cancer
• Figure 16: Future trends in HER2+ breast cancer
• Figure 17: Tukysa for Breast Cancer (May 29, 2020): Phase II - HER2CLIMB
• Figure 18: Kadcyla for Breast Cancer (May 13, 2020): Phase III - KAITLIN (w/Perjeta, HER2+)
• Figure 19: Enhertu for Breast Cancer (December 11, 2019): Phase II - DESTINY-Breast01 (HER2+)
• Figure 20: Margetuximab for Breast Cancer (October 22, 2019): Phase III - SOPHIA (HER2+)
• Figure 21: Tukysa for Breast Cancer (October 21, 2019): Phase II - HER2CLIMB
• Figure 22: Verzenio for Breast Cancer (September 28, 2019): Phase II - monarcHER
• Figure 23: Key upcoming events in breast cancer (one of two)
• Figure 24: Key upcoming events in breast cancer (two of two)
• Figure 25: Unmet needs in HER2+ breast cancer

LIST OF TABLES

• Table 1: Preferred branded treatments for HER2+ breast cancer
• Table 2: Incident cases of breast cancer, 2018-27
• Table 3: Five-year prevalent cases of breast cancer, 2018-27
• Table 4: Breast cancer subtypes
• Table 5: Marketed drugs for HER2+ breast cancer
• Table 6: Pipeline drugs for HER2+ breast cancer in the US
• Table 7: Historical global sales, by drug ($m), 2015-19
• Table 8: Forecasted global sales, by drug ($m), 2020-24
• Table 9: Tukysa for Breast Cancer (May 29, 2020)
• Table 10: Kadcyla for Breast Cancer (May 13, 2020)
• Table 11: Onzeald for Breast Cancer (February 27, 2020)
• Table 12: Leronlimab for Breast Cancer (January 31, 2020)
• Table 13: Oral Paclitaxel for Breast Cancer (December 13, 2019)
• Table 14: Phesgo for Breast Cancer (December 12, 2019)
• Table 15: Enhertu for Breast Cancer (December 11, 2019)
• Table 16: Tukysa for Breast Cancer (December 11, 2019)
• Table 17: MCLA-128 for Breast Cancer (October 23, 2019)
• Table 18: Margetuximab for Breast Cancer (October 22, 2019)
• Table 19: Tukysa for Breast Cancer (October 21, 2019)
• Table 20: Verzenio for Breast Cancer (September 28, 2019)