EMA Recommends Refusal of the Marketing Authorisation for Neratinib

It was intended for the treatment of patients with HER2-positive early breast cancer who had already received trastuzumab, but who were at high risk of cancer recurrence

On 22 February 2018, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorisation for the medicinal product neratinib (Nerlynx), intended for the treatment of breast cancer. 

The company that applied for authorisation is Puma Biotechnology Ltd. It may request a re-examination of the opinion within 15 days of receipt of notification of this negative opinion. 

Nerlynx is a medicine that contains the active substance neratinib. It was to be available as tablets. 

Nerlynx was expected to be used to treat adults with HER2-positive early breast cancer who had already had treatment that included trastuzumab, but who were at high risk of cancer recurrence.   

The active substance in Nerlynx, neratinib, is a tyrosine kinase inhibitor. It attaches to the HER2 protein on the cancer cells, and so blocks its action. Because HER2 helps cancer cells to grow and divide, blocking it helps to stop them growing and prevent the cancer coming back. 

The company provided the results from one main study involving 2,840 women with HER2-positive early breast cancer who had already received treatment that included trastuzumab. In these women, daily treatment with Nerlynx for a year was compared with placebo. The main measure of effectiveness was the proportion of women who had lived without the cancer coming back at the end of the 2-year study. 

The CHMP considered that a greater proportion of women given Nerlynx in the study lived for 2 years without their disease coming back than women given placebo (around 94% versus 92% respectively). However, it is uncertain that this difference in benefit would be seen in clinical practice. Furthermore, Nerlynx causes side effects in the digestive system, particularly diarrhoea, which affected most patients and might be difficult to manage. 

The Committee therefore concluded that the benefits were not enough to outweigh the risk of side effects and recommended that Nerlynx be refused marketing authorisation. 

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