Just days after their lead drug-device combination was voted down by FDA advisors, Nektar and Bayer have been hit by a phase 3 failure in another partnered program.
In the latest setback, the two companies have revealed that Amikacin Inhale (NKTR-061)—their combination of the antibiotic amikacin and a novel nebulizer delivery system—performed no better than placebo when used to treat Gram-negative pneumonia in patients on ventilators. Ahead of the news. the product had been tipped to become a $300 million-plus product by analysts.
Just last week, Nektar and Bayer’s ciprofloxacin-based Cipro Inhale combination, submitted for approval as a therapy to reduce exacerbations in adults with non-cystic fibrosis bronchiectasis and bacterial respiratory pathogens, was turned down by an FDA advisory committee on the grounds that data in trials was inconsistent and failed to show clear evidence of efficacy.
The INHALE trial in 725 patients hoped to demonstrate that layering Amikacin Inhale on top of the standard antibiotic regimens used to tackle Gram-negative pneumonia in intubated and mechanically ventilated patients would improve overall survival at 28 days compared to placebo. It failed to do so, and also failed to improve a series of secondary outcome measures including the number of days on mechanical ventilation and in intensive care.
Both the Cipro Inhale and Amikacin Inhale programs rest on the premise that using pulmonary delivery devices to achieve higher antibiotic concentrations within the lung can improve on the efficacy seen with systemically-administered antibiotics.
The device deployed in Amikacin Inhale is a vibrating mesh nebulizer that can be integrated into mechanical ventilation units or used ‘off vent’ as a hand-held device for patents who no longer need breathing assistance, according to Nektar. The combination is able to achieve lung levels of the antibiotic that are 1,000-fold higher than systemic delivery.
In the case of Cipro Inhale, which was given via a dry powder inhaler as an alternative to systemic antibiotics in trials, there was also a concern that low drug levels outside the lungs could encourage the emergence of resistance. The FDA is due to deliver a verdict on the drug.
Cipro Inhale and Amikacin Inhale were excluded from a 2008 deal in which Nektar sold off its pulmonary delivery business to Novartis for $115 million. Bayer licensed rights to the amikacin product for $175 million in 2007.
“The results of the INHALE study are disappointing, considering that morbidity and mortality remain significant in these patients. However, the study provides important clinical data for this difficult-to-treat disease,” said Bayer’s head of development Joerg Moeller.