EU regulators reject Puma's Nerlynx breast cancer drug

Radiology technician examens mammography test on location

European regulators have rejected Puma’s breast cancer drug Nerlynx (neratinib) – diverging from the FDA, which opted to grant the drug a licence last year.

Safety had been a concern for the FDA, but its expert advisers still said that on balance the drug’s benefits outweighed its risks in a meeting last May.

The FDA went on to approve Nerlynx in July last year in the extended adjuvant treatment of adults with early-stage HER2 positive breast cancer after Herceptin-based therapy.

Not so Europe’s CHMP regulatory committee, which based on the same clinical data noted that a greater proportion of women (94%) were alive in a trial arm treated with Nerlynx than with placebo (92%).

But the committee said this marginal benefit was outweighed by the side effects Nerlynx causes with the digestive system, particularly diarrhoea, which affected most patients and might be difficult to manage.

Roche has also applied for an extended label for its cancer drug Perjeta (pertuzumab) in combination with Herceptin (trastuzumab) in the same indication in Europe.

The FDA has approved Roche’s combination, which also produce a very marginal survival benefit, but with a more favourable side-effect profile and much lower occurrence of diarrhoea.

Puma had already signalled that the CHMP was unlikely to give a positive opinion on Nerlynx, which would have almost certainly have led to a European licence within the next few months.

But Puma said it plans to ask the CHMP to re-examine the dossier on Nerlynx, within the 15-day timeframe required under European regulations.

The CHMP’s vote was based on the results from both the phase 3 ExteNET trial in extended adjuvant early stage HER2-positive breast cancer and the phase 2 CONTROL trial in extended adjuvant early stage HER2-positive breast cancer.

An oral medicine, Nerlynx is a tyrosine kinase inhibitor that was originally developed by Wyeth, but dumped by Pfizer after the companies merged in 2009. Puma bought the rights to Nerlynx in 2011.