- Insys Therapeutics said Friday that the Food and Drug Administration issued it a Complete Response Letter rejecting the company’s New Drug Application for Buvaya. The product is a sublingual spray form of buprenorphine, an opioid analgesic.
- The FDA ruling, as well as the findings of two FDA advisory committees in May, cited lack of efficacy as well concerns about side effects and safety as the reasons for the drug’s rejection.
- The rejection of Buvaya was just the latest problem for Insys, which has been accused of bribing doctors into prescribing Subsys, the company’s sublingual fentanyl spray. Insys founder John Kapoor and six other former executives have been criminally charged in the case.
At the joint meeting of the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee and its Drug Safety and Risk Management Advisory Committee in May, advisers voted 18-1 against approval of Buvaya. In the pivotal trial of the sublingual spray, the shortest median time to pain relief was 92 minutes at the highest dose of .5 mg. This delay in pain relief could cause patients to take another dose of the drug, or they might reach for another opioid to obtain pain relief, advisers said. As a result, patients could be in danger of unintentionally misusing the drug, and suffering an overdose.
The FDA panel was also concerned about adverse events with the drug — particularly potentially deadly hypoxia, or oxygen deficiency. Along with hypoxia, side effects of nausea and vomiting caused some participants in the clinical trials of Buvaya to discontinue the drug. Compared to standard pain therapies, Buvaya produced double the rate of nausea and four times the rate of vomiting.
Panel members commented that the high rate of vomiting could lead to more pain for patients and poor compliance with treatment.
Insys argued in its presentation that Buvaya, a Schedule III drug, had a reduced risk for addiction, overdose and death compared to other opioids. Scientific literature indicates that buprenorphine is not known as a popular drug for recreational use, Insys’ representatives said.
But at least one adviser at the FDA committee noted that data does show some people abuse buprenorphine for its euphoric effect.
In a statement about the CRL, Insys said it continues to value the new proprietary buprenorphine formulation as a means for relieving pain effectively and will assess next steps in the coming months.