A US Food and Drug Administration advisory panel is set to convene later today to decide whether to back Chiron’s lung transplant drug, Pulminiq (cyclosporine), for approval. However, briefing documents released ahead of the meeting suggested that the agency does not believe the treatment made a difference.
In its pre-meeting papers, the agency said that a small Phase II clinical trial designed to “show a treatment difference in terms of acute rejection… failed to achieve that objective.” Furthermore, the documents suggest that any survival benefit seen with Chiron’s drug may be due to patient imbalances across treatment groups in the pivotal study. Randomisation in the trial “was not stratified by single versus double lung transplant, or other baseline donor/recipient characteristics known to influence long term survival,” the agency’s briefing document stated. In the study, 58% of Pulminiq patients had a single transplant versus 80% of patients on placebo, while 42% of Pulminiq patients had a double transplant, versus 20% on placebo. Although the imbalances might not pose a serious problem, the FDA said that it would be a potential issue when evaluating patient survival. “These imbalances would be expected to predict worse patient long-term survival in the placebo group,” the FDA said, adding that patients with single lung transplant have a worse prognosis than patients with double lung transplant one year after transplant and beyond.
The agency is also expected to question the safety of the drug as an aerosolised agent. It noted that the safety database for aerosolised cyclosporine is small in the lung transplant population and that the vehicle being proposed for the final product (propylene glycol) was not used in the studies. Preclinical studies with propylene glycol show that dogs given the vehicle over 28 days develop lung inflammation. Overall, Pulminiq patients had more respiratory system adverse events than placebo patients in the trials.
