[Updated 1/15/2020, 8:51 a.m. See below.] As the nation grapples with the ongoing opioid crisis, an FDA advisory panel on Tuesday unanimously voted against recommending approval of a Nektar Therapeutics painkiller that would add a new compound to the drug class—even though it was designed to reduce the risk of abuse.
Some members of the panel, which was comprised mainly of physicians and pharmacists, said Nektar (NASDAQ: NKTR) did not provide enough data to support its claims. Others expressed concern that an approval could send the message that the San Francisco company’s drug is a “safer opioid.” Overall, panelists said that they want more clinical data. At the end of the daylong meeting, the vote tally was 27-0 opposing approval.
The FDA is not obligated to follow advisory panel recommendations, but these comments are considered in the agency’s drug decisions. Nektar isn’t waiting to see what the FDA decides. Late Tuesday, the company announced it is withdrawing its application and will make no further investment in the program. [Paragraph updated with Nektar statement.]
The Nektar drug, oxycodegol (formerly known as NKTR-181), is an opioid that, similar to other drugs in the class, binds to the mu-opioid receptor to provide its analgesic effect. Nektar designed its drug so that the compound crosses the blood brain barrier more slowly compared to oxycodone. The company adds that its drug more slowly activates receptors compared to other opioids.
In documents submitted to the FDA, Nektar says these features reduce the euphoric effect a patient would experience compared to other opioids. The company adds that, unlike currently available opioids, oxycodegol’s abuse-deterrent features cannot be compromised because they are “inherent properties of the NKTR-181 molecule.”
Nektar has applied for approval of oxycodegol as a treatment for moderate-to-severe chronic low back pain in adults who need daily, around the clock pain management. The company is seeking approval for that use even though previous advisory committees have raised concerns about approving an opioid to treat patients for whom opioids are not currently a main treatment, according to FDA documents. That’s not the only red flag. Nektar submitted its drug application based on data from a single Phase 3 study despite FDA recommendations that the company conduct a second study to confirm the drug’s efficacy.
In the single Phase 3 study, which enrolled 1,190 patients, the Nektar drug met the main goal of reducing average pain compared to a placebo. But some panel members questioned whether that was enough. Laura Block, a clinical pharmacist at Usagi Medical Group in Cary, NC, said oxycodegol is “potentially very promising” but she wants to see more data from a large Phase 3 study testing the drug in a variety of pain patients, not just those who have low back pain. Martin Garcia-Bunuel, deputy chief of staff at the Veterans Affairs Maryland Health Care System, questioned whether the study was strong enough to support the case that the drug was effective. He added that he’s concerned about approving another opioid without more robust data.
In addition to more efficacy data, Kevin Zacharoff, a professor at the State University of New York’s Stony Brook School of Medicine, said he wants more information about what happens if someone tries to inject or inhale oxycodegol. He also said that more than patient safety, any decision about the drug must weigh the drug’s impact on other members of a household, the community, and society overall. But Zacharoff also said that designing a molecule to reach the brain more slowly is a promising approach for a new opioid. “With the right data and the right amount of information, it could have been a yes from me,” he said.
Steven Meisel of Fairview Health Services in Minneapolis, expressed concern that approval of oxycodegol could convey that the drug is a safer opioid—a potentially dangerous public health message. He added that the marketing of a new opioid painkiller could turn it into a blockbuster drug without sufficient data to show that its benefits outweigh the risks.
“We can’t approve a blockbuster drug in the middle of a public health crisis based on speculation,” Meisel said.