Six months af­ter Puma Biotech­nol­o­gy won an FDA OK for its can­cer ther­a­py ner­a­tinib, the EMA looks like its prepar­ing to throw up a big road­block in­to Eu­rope over con­cerns its reg­u­la­tors have about the drug. And the news im­me­di­ate­ly trig­gered an­oth­er sharp turn for the biotech’s stock $PBYI, which plunged 27% in af­ter-mar­ket trad­ing.

An­a­lysts have been fret­ting over the Eu­ro­pean de­ci­sion for months now, not­ing that a sci­en­tif­ic ad­vi­so­ry group meet­ing called by the EMA sug­gest­ed that Puma faced some broad chal­lenges that ex­tend­ed be­yond the ev­i­dence of se­vere di­ar­rhea linked to the drug.

Alan Auer­bach, Puma CEO

To­day Puma an­nounced that the CHMP no­ti­fied the com­pa­ny of a neg­a­tive trend vote, which loose­ly trans­lat­ed means that they are high­ly un­like­ly to get a green light in Eu­rope any­time soon to sell ner­a­tinib for the ex­tend­ed ad­ju­vant treat­ment of ear­ly stage HER2-pos­i­tive breast can­cer.

The com­pa­ny’s state­ment not­ed:

CHMP in­di­cat­ed that, in its opin­ion, the ben­e­fit risk as­sess­ment is neg­a­tive as the study re­sults are based on ev­i­dence from a sin­gle piv­otal tri­al and the 2- and 5-year in­va­sive dis­ease free sur­vival (iDFS) ben­e­fits ob­served to-date may lack suf­fi­cient clin­i­cal rel­e­vance.

That will like­ly make Puma’s jour­ney in search of an ap­proval in Eu­rope much, much longer, while it’s free to sell the drug in the US.

Leerink’s Michael Schmidt not­ed:

CHMP’s opin­ion was based on the re­sults from both the Phase III Ex­teNET tri­al in ex­tend­ed ad­ju­vant ear­ly stage HER2-pos­i­tive breast can­cer and the Phase II CON­TROL tri­al in ex­tend­ed ad­ju­vant ear­ly stage HER2-pos­i­tive breast can­cer ac­cord­ing to PBYI. In con­trast to that, the US FDA On­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee (ODAC) vot­ed 12:4 in fa­vor of FDA ap­proval in­di­cat­ing that the risk-ben­e­fit pro­file of Ner­l­ynx was fa­vor­able. The FDA sub­se­quent­ly ap­proved Ner­l­ynx with a broad la­bel in the US which is not lim­it­ed to cer­tain pa­tient sub-pop­u­la­tions.

The de­bate over grade 3 di­ar­rhea seen in clin­i­cal tri­als ex­cit­ed con­sid­er­able short in­ter­est in the stock, but the FDA’s ad­vis­ers bare­ly hes­i­tat­ed in urg­ing an ap­proval, with a track record that has long fa­vored adding new op­tions for on­col­o­gists and patents when­ev­er pos­si­ble.

Puma’s shares — al­ways volatile in the back-and-forth de­bate over the drug’s side ef­fects and its ef­fi­ca­cy — dived 27% in­stant­ly.

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

A California judge will allow a plaintiff in a state court case to introduce expert testimony connecting a potential carcinogen in former blockbuster medicine Zantac to cancer.

The order was handed down on Thursday from state judge Evelio Grillo, who is now allowing both parties to introduce expert testimony in an upcoming trial after what’s known as a Sargon hearing, where a judge determines the admissibility of expert witnesses and expert opinions.