Nature: Breast Cancer Therapies And Market Forecast

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Nature: Breast Cancer Therapies And Market Forecast Breast cancer is the most common cancer among women, and it is also the cancer with the most cancer-related deaths among women worldwide. According to the latest global cancer burden data released by the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO) in 2020, the number of new breast cancer cases worldwide reached 2.26 million in 2020, surpassing lung cancer (2.21 million cases) for the first time to become the world's largest cancer. China is a major breast cancer country.

In 2020, about 420,000 new cases of breast cancer occured and nearly 120,000 deaths caused.

Breast cancer is a heterogeneous malignant tumor, according to estrogen receptor (ER) and progesterone receptor (PR)(collectively called hormone receptor HRs) and human epidermal growth factor receptor 2 (HER2, also called ERBB2) ) is divided into different subtypes. HR and HER2 status determine the medicine regimen.

Current Therapies 1. HER2-positive breast cancer About 20% of breast cancers are HER2 positive breast cancer. Trastuzumab (Herceptin, Roche) was the first HER2 targeted drug approved (1998). Since then, a large number of HER2 targeted drugs have been approved, including pertuzumab (Perjeta, Roche), trastuzumab emtansine (T-DM1; Kadcyla, Roche), lapatinib (Tykerb/Tyverb, Novartis), neratinib (Nerlynx, Puma) , Trastuzumab deruxtecan (Enhertu, Daiichi Sankyo/AstraZeneca), tucatinib (Tukysa, Seagen/Pfizer) and margetuximab (Margenza, MacroGenics).

Trastuzumab plus chemotherapy, with or without pertuzumab is the standard of adjuvant or neoadjuvant treatment for early disease.

Trastuzumab emtansine and neratinib are adjuvant treatment options. Pertuzumab plus trastuzumab combined with chemotherapy is the first-line standard treatment for metastatic disease, and trastuzumab emtansine is the second-line standard treatment for metastatic disease.

However, trastuzumab-drutecan (approved in 2019), tucatinib plus trastuzumab and capecitabine, neratinib plus capecitabine and magituximab plus chemotherapy (all approved in 2020) began to preempt the prescriptions of trastuzumab-entaxine and trastuzumab for the treatment of recurrent diseases.

Trastuzumab-druxicam is also being tested as a neoadjuvant therapy, and tucatinib

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combined with trastuzumab-entanine is also being used for trastuzumab treatment and taxane treatment for late or patients with metastatic disease.

2. HR positive/HER2 negative breast cancer Early disease is treated with hormones, usually takes 5-10 years. Patients with intermediate and high-risk diseases can also receive chemotherapy before hormone therapy.

CDK4/6 inhibitors: palbociclib (Ibrance, Pfizer), ribociclib (Kisqali, Novartis) or abemaciclib (Verzenio/Verzenios/Virginio, Eli Lilly) combined with endocrine therapy is the first-line treatment standard for metastatic breast cancer.

PI3K inhibitors: In 2019, the FDA approved the PI3K inhibitor alpelisib (Piqray, Novartis) to treat advanced or metastatic breast cancer with PIK3CA mutations (about 40% of patients).

Everolimus (Afinitor, Novartis) combined with exemestane is also a treatment option for HR-positive/HER2-negative recurrent breast cancer.

3. Triple negative breast cancer PDL1 inhibitors: In 2019, the PDL1 inhibitor atezolizumab (Tecentriq, Roche) combined with nano-paclitaxel (Abraxane, Celgene) for the treatment of PDL1-positive (about 40% of patients) advanced or metastatic disease received accelerated FDA approval.

In November 2020, the FDA approved the PD1 inhibitor pembrolizumab (Keytruda, Merck & Co.) combined with chemotherapy to treat patients with locally recurrent unresectable or metastatic triple-negative breast cancer expressing PDL1.

PARP inhibitors: Two PARP inhibitors are approved for advanced or metastatic breast cancer with BRCA1/2 mutation and HER2-negative after chemotherapy. The prevalence of BRCA1/2 mutations in triple-negative (15%) and HR-positive/HER2-negative (3–4%) breast cancers is low. Olapali (Lynparza, AstraZeneca) was the first to be marketed, followed by Talzenna (Pfizer) (both drugs were approved by the FDA in 2018).

TROP2 inhibitor: Sacituzumab-govitecan (Trodelvy, Immunomedics) is an ADC drug targeting TROP2, which received accelerated FDA approval in 2020.

Novel Therapies The treatment pathways for advanced breast cancer are diverse, spanning approved drug categories and new mechanisms of action (including AKT and CXCR4 inhibitors) in

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different treatment environments.

1. HER2-ADC drug: Trastuzumab duocarmazine (Byondis) is a HER2-targeted ADC that is currently being evaluated for advanced or metastatic HER2-positive breast cancer (TULIP trial).

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2. PD1 inhibitor: nivolumab (Opdivo, Bristol-Myers Squibb/Ono) is being developed for early, previously untreated, ER-positive/negative high-risk breast cancer (CheckMate 7FL trial).

3. AKT inhibitors: Two AKT inhibitors are under development for advanced and metastatic breast cancer. One of them, ipatazitib (Roche) plus chemotherapy is being evaluated as a first-line treatment for triple-negative disease with atezolizumab (ipatinib).

However, the preliminary results of the IPATunity130 trial failed to prove the clinical efficacy of ipatasertib combined with paclitaxel.

4. CXCR4 inhibitor: Balixafortide (Polyphor) is a CXCR4 inhibitor. It is being combined with eribulin (Halaven, Eisai) to treat HER2-negative recurrent or metastatic breast cancer.

Veliparib (AbbVie) has also been developed for patients with HER2-negative but BRCA1/2 mutated tumors. Unlike the approved PARP inhibitors, Veliparib is undergoing clinical evaluation of combination chemotherapy.

5. Hormone therapy: elacestrant (Radius Health) and lasofoxifene (Sermonix Pharmaceuticals) are in key trials for the treatment of ER-positive/HER2-negative metastatic breast cancer.

6. Others: including two oral taxanes, a PI3K inhibitor and a vaccine against globoh are also in the experiment.

Market Forecast In 2019, the breast cancer market totaled $20.2 billion, mainly from HER2 or CDK4/6 therapeutic drugs (68% of sales). Despite increasing competition from generics and biosimilars, we predict that the breast cancer market is expected to grow by 9% annually to reach $47.7 billion in 2019-2029(Figure 1). The continued use and expansion of CDK4/6 inhibitors, as well as the entry of 14 high-priced drugs, will drive continued sales growth.

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Major market sales of key breast cancer therapiess estimated by drug category The chart shows the forecast for the seven major markets of the USA, France, Germany, Italy, Spain, the UK and Japan for 2019-2029.

By 2029, CDK4/6 and HER2 targeted drugs are expected to maintain their share of breast cancer sales (73%), approximately $20 billion and $15 billion, respectively.

Trastuzumab-deruxtecan is expected to become the best-selling HER2 targeted drug due to its wide application and long treatment time for HER2-positive, HR-positive/HER2-negative and triple-negative tumors.

Sales of two CDK4/6 inhibitors (abemaciclib and ribociclib) for early HR-positive/HER2-negative breast cancer will also continue to grow, and we predict that they will increase to $14 billion in 2029 (accounting for 69% of drug sales) , Abemaciclib will contribute $13 billion (94%).

It is expected that new drugs will enter the breast cancer market, providing diversified treatment options for triple-negative and HR-positive/HER2-negative patients. However, the sales of some therapies will be restricted by the population defined by their biomarkers, approval of smaller advanced populations, and strong competition between existing and emerging therapies.

As a world leading supplier of PEG derivatives, pharmaceutical intermediates and research chemicals, Huateng Pharma provides anti-cancer intermediate products for

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some drugs, such as Palbociclib and Ribociclib which used for the treatment of certain kinds of breast cancer. Both Palbociclib and Ribociclib are inhibitors of CDK4 and CDK6. Sacituzumab Govitecan (IMMU-132) is an ADC drug approved in 2020 which used to treat adults triple-negative breast cancer. We are able to supply product 2-((Azido-PEG8-carbamoyl)methoxy)acetic acid, CAS NO.: 846549-37-9 with variety quantities based on customers’ demand, it is a fragment of IMMU-132.

References: The breast cancer drug market Related Articles: [1] CDK4/6 Inhibitors for Treatment of Advanced Breast Cancer [2] Palbociclib Combined With Paclitaxel Shows Effective For The Treatment Of ER Positive Breast Cancer [3] CDK4/6 Inhibitors: How Do They Work against Breast Cancer?