Withdrawal of Application for a Change to the EU Marketing Authorisation for Nivolumab

It was expected to be used to treat also gastric cancer, including gastro-oesophageal junction cancer

On 27 June 2018, Bristol-Myers Squibb Pharma EEIG officially notified the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for a new use of nivolumab (Opdivo) for the treatment of stomach cancer. 

Opdivo is a cancer medicine currently authorised to treat melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, squamous cell cancer of the head and neck, and urothelial cancer. 

Opdivo has been authorised since June 2015 and contains the active substance nivolumab. 

Opdivo was expected to be used to treat also gastric cancer, including gastro-oesophageal junction cancer. 

The active substance in Opdivo, nivolumab, is a monoclonal antibody. Nivolumab attaches to a PD-1 receptor which is found on T cells. Cancer cells can produce proteins (PD-L1 and PD-L2) that attach to this receptor and switch off the activity of the T cells, preventing them from attacking the cancer. By attaching to the receptor, nivolumab prevents PD-L1 and PD-L2 from switching off the T cells, thereby increasing the ability of the immune system to kill cancer cells. 

What did the company present to support its application?

The company presented data from a main study comparing Opdivo with placebo in 493 patients with gastric cancer gastro-oesophageal junction cancer. All patients were Japanese, Korean or Taiwanese and had recurring cancer that could not be surgically removed or treated with standard therapy. The study looked at how long the patients lived while taking Opdivo. 

How far into the evaluation was the application when it was withdrawn? 

The application was withdrawn after the CHMP had evaluated the documentation provided by the company and formulated lists of questions. After the CHMP had assessed the company’s responses to the questions, there were still some unresolved issues. 

What was the recommendation of the CHMP at that time? 

Based on the review of the data and the company’s response to the CHMP lists of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Opdivo could not have been approved for the treatment of stomach cancer. 

The CHMP noted that in the main study Opdivo treatment led to a limited improvement in survival (around 1 month). Furthermore, it was not clear that even this benefit would be seen in European patients, as the patients in the study were from populations who are known to be affected differently by stomach cancer. In the absence of further data, it was

not possible to establish that the benefits of Opdivo outweighed its risks for European patients. Therefore, at the time of the withdrawal, the CHMP was of the opinion that a benefit of Opdivo in the treatment of stomach cancer had not been demonstrated. 

What were the reasons given by the company for withdrawing the application? 

In its letter notifying the Agency of the withdrawal of application, the company stated that it was withdrawing because of the remaining uncertainties which would not allow the CHMP to conclude that the benefits outweighed the risks at the present time. 

The company informed the CHMP that there are no consequences for patients currently included in clinical trials using Opdivo. 

There are no consequences for Opdivo in its authorised uses.