EU cancer drugs rejection shows contrasts with FDA

Europe’s expert medicines panel has rejected Puma Biotechnology’s breast cancer drug neratinib, citing limitations in its efficacy and safety concerns.

The rejection of neratinib on Friday by the European Medicines Agency’s CHMP didn’t come as a surprise, as Puma had warned in January that this was the likely outcome, and saw its share price plunge at the time.

But the decision is most notable because it is a rare contrast with the FDA – which approved the drug under the brand name Nerlyx last year.

The drug was in fact one of three the CHMP voted against, also rejecting expanding indications of two other cancer drugs – Gilead’s Zydelig and Pfizer’s Sutent – because of similar doubts about their benefit/risk profiles.




Nerlynx is the first extended adjuvant therapy, a form of therapy for women with HER2+ breast cancer.  This means it is taken after an initial treatment with Herceptin to further lower the risk of the cancer coming back.

Puma’s data shows that its benefits over placebo are narrow – 94% of women in its pivotal study lived for 2 years without their disease coming back, compared to 92% on placebo.

The CHMP said it was “uncertain that this difference in benefit would be seen in clinical practice.” Furthermore, it pointed out that the drug causes side effects in the digestive system, particularly diarrhoea, which affected most patients and which it said could be difficult to manage.

Puma now has the chance to seek a re-examination of the opinion, and the company says it will take up this opportunity by submitting a request for this second review shortly.

The decision raises the question of whether the US FDA and Europe’s EMA are diverging in their general approach to benefit/risk profiles. Last year saw the FDA approve a record 46 novel drugs approved in 2017.

Market analysts had been doubtful about the drug’s chances of FDA approval, based on its less-than-compelling efficacy data and the sometimes very serious diarrohea it causes in a large proportion of patients. Its approval sparked debate in the US, particularly as it came just months after the Trump-appointed Scott Gottlieb took the helm at the FDA.

The US regulator instructed that the drug should be co-administered with given loperamide and additional diarrohea treatments to manage the side-effects.

The Nerlynx approval was one of the most scrutinised by FDA observers for signs of a weakening in its oversight. Some US oncologists made it clear they saw a very limited role for the drug in the market, and this may well be reflected in limited sales in the US in 2018.

Concerns that Gottlieb would oversee a dangerous lowering of the FDA’s standards have now receded, but the CHMP’s decisions suggest it is taking a more conservative line than its US counterpart, especially in treatments for patients with advanced cancer where benefits might be limited.

This trend isn’t entirely new – another example is the US approval of Roche’s Avastin in glioblastoma, which was refused approval in Europe in 2014.

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