EMA Recommends Granting a Marketing Authorisation for Trastuzumab Biosimilar

Ontruzant is intended for the treatment of early and metastatic breast cancer, and metastatic gastric cancer

On 14 September 2017, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending granting a marketing authorisation for the biosimilar medicinal product trastuzumab (Ontruzant), intended for the treatment of early and metastatic breast cancer, and metastatic gastric cancer.

The applicant for this medicinal product is Samsung Bioepis UK Limited (SBUK).

Ontruzant will be available as a 150 mg powder for concentrate for solution for infusion. The active substance of Ontruzant is trastuzumab, a monoclonal antibody (ATC code: L01XC03) that binds with high affinity and specificity to HER2 leading to the inhibition of the proliferation of tumour cells that overexpress HER2.

Ontruzant is a biosimilar medicinal product. It is highly similar to the reference product Herceptin (trastuzumab), which was authorised in the EU on 28 August 2000. Data show that Ontruzant has comparable quality, safety and efficacy to Herceptin (trastuzumab).

The full indication is:

"Metastatic breast cancer

Ontruzant is indicated for the treatment of adult patients with HER2 positive metastatic breast cancer (MBC):

  • as monotherapy for the treatment of those patients who have received at least two chemotherapy regimens for their metastatic disease. Prior chemotherapy must have included at least an anthracycline and a taxane unless patients are unsuitable for these treatments. Hormone receptor positive patients must also have failed hormonal therapy, unless patients are unsuitable for these treatments.
  • in combination with paclitaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease and for whom an anthracycline is not suitable.
  • in combination with docetaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease.
  • in combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive MBC, not previously treated with trastuzumab.

Early breast cancer

Ontruzant is indicated for the treatment of adult patients with HER2 positive early breast cancer (EBC).

  • following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable).
  • following adjuvant chemotherapy with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel.
  • in combination with adjuvant chemotherapy consisting of docetaxel and carboplatin.
  • in combination with neoadjuvant chemotherapy followed by adjuvant Ontruzant therapy, for locally advanced (including inflammatory) disease or tumours >2 cm in diameter.

Ontruzant should only be used in patients with metastatic or early breast cancer whose tumours have either HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay.

Metastatic gastric cancer

Ontruzant in combination with capecitabine or 5-fluorouracil and cisplatin is indicated for the treatment of adult patients with HER2 positive metastatic adenocarcinoma of the stomach or gastro-oesophageal junction who have not received prior anti-cancer treatment for their metastatic disease.

Ontruzant should only be used in patients with metastatic gastric cancer (MGC) whose tumours have HER2 overexpression as defined by IHC2+ and a confirmatory SISH or FISH result, or by an IHC 3+ result. Accurate and validated assay methods should be used."

It is proposed that Ontruzant should only be initiated by a physician experienced in the administration of cytotoxic chemotherapy, and should be administered by a healthcare professional only.

Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.

Summaries of positive opinion are published without prejudice to the Commission decision, which will normally be issued 67 days from adoption of the opinion.

Withdrawal of the marketing authorisation application for biosimilar trastuzumab (Ogivri)

On 3 August 2017, Mylan S.A.S. officially notified the CHMP that it wishes to withdraw its application for a marketing authorisation for Ogivri, for the treatment of breast cancer and gastric cancer.

Ogivri is a medicine that contains the active substance trastuzumab. It was to be available as a powder to be made up into a solution for infusion into a vein.

Ogivri was developed as a biosimilar medicine. It was intended to be highly similar to a biological medicine (the reference medicine) already authorised in the European Union as Herceptin.

Ogivri was expected to be used to treat early and metastatic breast cancer and metastatic gastric cancer. Ogivri was to be used only when the cancer has been shown to overexpress HER2. HER2 is overexpressed in about a quarter of breast cancers and a fifth of gastric cancers.

The active substance in Ogivri and Herceptin, trastuzumab, is a monoclonal antibody. A monoclonal antibody is an antibody that has been designed to recognise and attach to an antigen that is found on certain cells in the body. Trastuzumab has been designed to attach to HER2. By attaching to HER2, trastuzumab activates cells of the immune system, which then kill the tumour cells. Trastuzumab also stops HER2 producing signals that cause the tumour cells to grow.

The company presented results of studies on the quality, safety and effectiveness of the medicine. Two studies were carried out in healthy volunteers to investigate whether Ogivri produces the same levels of the active substance in the body as the reference medicine Herceptin and therefore has the same effect. In a third study, Ogivri in combination with a taxane was compared with Herceptin used in combination with a taxane in 500 patients with metastatic breast cancer whose tumour cells overexpressed HER2. The study measured the number of patients who responded to treatment.

The application was withdrawn after the CHMP had evaluated the documentation provided by the company and formulated lists of questions. The company had not responded to the last round of questions at the time of the withdrawal.

Based on the review of the data at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Ogivri could not have been approved for the treatment of breast cancer and gastric cancer.

The CHMP’s main concern was the lack of a valid certificate confirming that the manufacturing facility of the product complies with good manufacturing practice (GMP) requirements. Therefore, at the time of the withdrawal, the CHMP was of the opinion that the company had not provided enough documentation to support the application for Ogivri.

In its letter notifying the Agency of the withdrawal of the application, the company stated that it was withdrawing the application because a GMP certificate for the manufacturing site of the product could not be obtained in the time available.

The company informed the CHMP that the withdrawal does not impact ongoing clinical trials with Ogivri.

If you are in a clinical trial and need more information about your treatment, contact the doctor who is giving it to you.