AstraZeneca's ADC and PARP Inhibitors Gain EU Backing for High-Risk Breast Cancer
AstraZeneca
Biopharmaceutical Manufacturer
Committee for Medicinal Products for Human Use
Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.
On June 27, according to Reuters, AstraZeneca said today that its existing Enhertu and Lynparza therapies have been recommended for the treatment of certain forms of high-risk breast cancer patients in the EU, which will boost the company's oncology portfolio.
ADCs are undoubtedly one of the most highly regarded types of drugs at present. As one of the representatives of ADCs, Enhertu has gained fame for quite some time. Over the past few years, this ADC drug, jointly developed and manufactured by Daiichi Sankyo and AstraZeneca, has become the preferred treatment option for breast cancer patients with HER2 protein overexpression.
In 2019, Enhertu was approved by the FDA for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received at least two prior anti-HER2 therapies. In 2021, it was further approved for adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received one or more anti-HER2 regimens.
Earlier in May, U.S. regulators approved Enhertu for second-line treatment, a move that could challenge Roche's long-standing dominance in the breast cancer field with its drug Perjeta (pertuzumab). Not long ago, Enhertu garnered significant attention at the 2022 ASCO Annual Meeting due to its groundbreaking breakthrough.
What made Enhertu stand out was a study named DESTINY-Breast04, which aimed to test the efficacy of Enhertu in patients with very low HER2 expression in tumors.
As is known to all, HER2 is a protein crucial for the growth of cells such as those in breast cancer. Accurately determining HER2 status is an essential principle in the molecular subtyping diagnosis of breast cancer, and HER2-targeted therapy represents a key treatment option for patients with HER2-positive breast cancer.
Previous HER2-targeted drugs were effective for HER2-positive patients overall but showed limited efficacy in the 80% of patients who were HER2-negative. However, it should be noted that 75% of these patients were not completely devoid of HER2 protein—they were simply "HER2-low." Due to the lack of treatment options, previous treatment regimens (chemotherapy) did not differentiate in this regard.
According to the introduction, Enhertu is designed using proprietary technology and does not need to function by inhibiting HER2 activity; HER2 expressed on tumor cells merely serves as a signal to guide the ADC in delivering cytotoxic drugs into the cell. Because of this, Enhertu can effectively target tumor cells with low HER2 expression and further kill nearby HER2-expressing cancer cells through the "bystander effect."
But according to the latest research published by AstraZeneca at the 2022 ASCO Annual Meeting, the treatment effect of Enhertu in breast cancer patients with "HER2-low expression" is significantly better than the current standard therapy. Specifically, Enhertu increased the overall median progression-free survival from 5.1 months to 9.9 months and the median overall survival from 16.8 months to 23.4 months. This means that precision treatment for breast cancer is expected to be further improved.
Reuters reported that the EMA has approved Enhertu for the treatment of aggressive breast cancer characterized by high HER2 expression. In addition, another drug named Lynparza has also received support from European regulators, either as a monotherapy or in combination with endocrine therapy, to be offered to adults with an early form of breast cancer carrying a specific genetic mutation.
By type, Lynparza is the world's first approved PARP inhibitor, currently capturing nearly 10 indications. This is partly due to the mechanism of PARP, which exploits the defect in the tumor DNA damage repair (DDR) pathway to preferentially kill cancer cells, giving Lynparza the potential to treat a wide range of tumors with DNA damage repair defects (such as BRCA1 and/or BRCA2 mutations).
In March, AstraZeneca and Merck announced additional positive results from the Phase III OlympiA trial (NCT02032823) of Lynparza at the 2022 ESMO Online Meeting.
The trial was conducted in adult patients with high-risk early breast cancer (eBC) who were HER2-negative, carried a germline BRCA mutation (gBRCAm), and had received neoadjuvant (pre-surgery) or adjuvant (post-surgery) chemotherapy. Data showed that, compared to placebo, Lynparza adjuvant treatment demonstrated a statistically significant improvement in overall survival (OS). OS was a key secondary endpoint of the trial.
Lynparza is the first and only PARP inhibitor to show an overall survival benefit in certain patients with early breast cancer. Specifically, compared with placebo, adjuvant treatment with Lynparza reduced the risk of death by 32%. The 3-year survival rate was 92.8% in the Lynparza group and 89.1% in the placebo group. The 4-year survival rate was 89.8% in the Lynparza group and 86.4% in the placebo group.
In other words, Lynparza can significantly reduce the risk of recurrence and improve survival in patients with high-risk early-stage breast cancer, which has the potential to alter the course of early-stage breast cancer and offer hope of a cure for patients.
Lynparza's compound patent will expire in March 2024, the formulation patent will expire in October 2029, and the use patent will expire in November 2024. However, AstraZeneca is also developing the next-generation PARP therapy AZD5305. Unlike the marketed PARP1/2 inhibitor Lynparza, AZD5305 has high selectivity for the PARP1 subtype, giving it the potential to overcome the side effects of currently marketed PARP inhibitors.
According to Evaluate Pharma's analysis, by 2028, Lynparza's annual sales are expected to double between 2021 and 2028. Clarivate analysts have also predicted that Enhertu’s global sales will exceed $6 billion by 2026. As these two blockbuster products expand into more markets, AstraZeneca's oncology business will undoubtedly be further strengthened.
Editor: Eight Corners
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