Welcome to your weekly digest of approaching regulatory and clinical readouts. Puma's (NYSE:PBYI) breast cancer project neratinib will go before a US panel on May 24, but Roche's (OTCQX:RHHBY) rival Perjeta could soon show clinical data that render neratinib almost irrelevant, and the recent departure of a senior member of Puma's staff has fueled rumors of a negative outcome at the adcom.

On the same day Emmaus Life Sciences will go before the same FDA panel for its sickle cell disease project Endari, currently availbale as a nutraceutical. Regulators have questioned the efficacy analysis in the past, but with few options for patients approval could still ensue.

Puma becomes the prey

In just over a week a panel will discuss Puma's neratinib for use as an adjuvant treatment in Her2-overexpressing breast cancer. The filing was based on the phase III Extenet trial, in which patients received neratinib monotherapy after a year's Herceptin.

Puma has a number of hurdles in its path, the biggest of which is Perjeta. A positive result in Roche's phase III Aphinity study indicated that Perjeta could potentially be practice-changing for breast cancer, and Puma's shares dropped 14% (Aphinity all but confirms Puma's worst nightmare, March 2, 2017).

Roche's trial gave patients Perjeta plus Herceptin for a year versus Herceptin alone. Details, including the extent of Perjeta's benefit, will appear at Asco on June 5.

Other issues for Puma include the severe diarrhea seen with neratinib, questions over neratinib's marginal benefit in Extenet trial, and large numbers of patients being censored.

This week Puma shares took another tumble on the news that its senior vice-president of regulatory affairs, Dr. Robert Charnas, would step down. Speculation that the resignation could be linked with the upcoming panel meeting, rather than the health reasons cited in the company's 8-K, caused shares to fall 16%.

Neratinib sales are forecast to reach $809m by 2022, according to sellside consensus from EvaluatePharma, but just over a year ago these sat at $2bn. Neratinib's PDUFA date is set for July; a strong benefit with Perjeta could be hard for the FDA to ignore.

Lacking options

Emmaus Life Sciences' Endari, in sickle cell disease, will also face the panel on May 24, and has a PDFUA date set for July 7.

The Californian group says that if Endari is approved it will become the first treatment for pediatric patients and the first new therapy in nearly 20 years for adult patients. However, it does not treat the underlying cause of the disease, instead aiming to reduce the frequency of the episodes of pain called sickle cell crises. It has orphan drug designation in the US and EU and US fast-track designation.

Endari is said to work by reducing oxidative damage to red blood cells. It consists of the amino acid L-glutamine as a nutritional supplement - the same active ingredient as the company's Nutrestore nutraceutical, available for short bowel syndrome in combination with recombinant human growth hormone. Endari is filed as a drug under the 505(b)(2) pathway.

The phase III trial was conducted in 230 patients aged five and over. It tested 0.3g/kg of L-glutamine twice daily for 48 weeks, up to a daily limit of 30g. The powder is mixed with water or certain non-heated foods.

The placebo comparator was the food additive maltodextrin, and two thirds of patients were on background hydroxyurea treatment, an established drug used to reduce crises. The company reported a 25% reduction in the median frequency of sickle cell crises, with Endari patients having a median of three over the 48-week trial.

Initially the company reported a p value of 0.063, above the pre-specified p value of 0.045. However, using a different analysis it said the results were "highly statistically significant" at 0.005.

The FDA had raised concerns over the primary endpoint analysis after the data were initially unblinded in 2014. Emmaus provided a report by an independent statistician explaining the significant results using the modified Ridit method, adjusting for varying strata or subgroup size, which in this case was region and hydroxyurea use.

No doubt the panel meeting will pay close attention to the statistical analyses used.

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Panel Woes For Puma And Statistical Uncertainties For Emmaus - Seeking Alpha