Nektar Therapeutics has been hit with a unanimous FDA panel rejection of its opioid painkiller, over concerns of drug abuse and lack of data.
The application for the drug – NKTR-181 – was submitted as a treatment for chronic lower back pain. However, an FDA panel comprised of independent advisers voted 27-0 against approval of the drug, taking issue with the drug misuse and the risks of addiction.
The panelists also cited concerns that a lack of data made it difficult to determine the possible abuse of the oral drug if it were to be snorted or injected, as well as its potential for liver toxicity.
According to Nektar, NKTR-181 provides the same levels of pain relief as standard opioid products, but with reduced central nervous system (CNS) side-effects, namely euphoria.
High levels of euphoric side-effects from opioid medications have lead to abuse and addiction, which has caused a healthcare crisis to erupt across the US.
Nektar’s drug avoids these side-effects because – according to the company – its molecular structure is designed to have low permeability across the blood-brain barrier, which causes a slow release into the brain and reduces the dopamine release that causes euphoria.
However, the FDA has disagreed with this notion, saying in a briefing document that it has “heard concerns that the approval of new opioid analgesics contributes to the prescription opioid crisis in the US by increasing the prescribing and availability of these products in the community”.
The panel also wanted to know if liver damage could occur at the higher doses of the drug, but a clinical study of NKTR-181 contained too few patients at the higher dose of 600mg twice daily to determine if this dose would lead to liver damage.
Although the rejection is a blow to Nektar, the opioid painkiller had already been somewhat sidelined because of its other promising pipeline immuno-oncology candidate.
The Bristol-Myers Squibb-partnered CD122-biased agonist NKTR-214 is due to start two new phase 3 studies soon, with the partners working on investigating the drug in 20 indications across a number of cancer types.
This includes studies, either underway or planned, in small cell lung cancer, breast cancer, colorectal cancer, gastric cancer, triple-negative breast cancer, sarcoma, melanoma, renal cell carcinoma, bladder cancer and non-small cell lung cancer.