Another opioid pain drug, really? FDA staff sound sour on Nektar analgesic
The crisis of opioid abuse, misuse, and overdose in the United States has made the FDA a tough critic of any opioid painkiller up for review. Nektar’s analgesic, NKTR-181, is no exception.
The drug is a reduced form of the widely-abused oxycodone — it is formulated in a way that increases the half-life and diminishes the rate of entry into the brain, according to Nektar, which believes that NKTR-181’s 16 times slower entry into the brain versus oxycodone will help deter abuse — but in briefing documents posted on Friday, FDA staff did not sound convinced, highlighting that the formulation is not engineered to facilitate abuse deterrence from physical manipulation.
In particular, agency reviewers underscored that NKTR-181 demonstrates an oral abuse potential comparable to oxycodone and that there was insufficient data to determine the abuse potential of the analgesic to allow a determination of abuse potential for NKTR-181 via the intravenous and intranasal route of administration.
Nektar — which spun the drug, once touted as a blockbuster, off into subsidiary operation, after initially seeking a partner — is looking for approval in patients with chronic low back pain. It tested the efficacy and safety of the analgesic in one late-stage trial and submitted safety data on patients with other chronic noncancer pain.
FDA reviewers asked the independent panel of advisors who will deliberate on the drug on Tuesday to ponder whether the one pivotal study backing the drug’s efficacy and safety was enough — considering Nektar was advised to conduct two trials.
Liver safety appeared to be another concern — FDA reviewers asked panelists to discuss whether any additional safety data are needed, considering patients may use NKTR-181 at doses higher than those tested.
In addition, reviewers appeared to ask panelists to deliberate whether the drug was necessary at all, given that opioids should not be used as the initial therapy for patients with chronic low back pain or those that have not responded adequately to non-opioid and non-pharmacologic therapies.
“Briefing documents released…read negatively to us, with language reflecting a lack of FDA comfort regarding the efficacy and safety of -181 and its potential for abuse. Consistent with the low expectations we had for program, we anticipate a majority vote against approval,” SVB Leerink’s Daina Graybosch wrote on Friday.
“We expect a tough reception for any opioid application given the ongoing public health crisis. There is nothing in the briefing docs to suggest that FDA sees anything in NKTR-181 to justify the safety risk of approving a new opioid to market. There are four draft questions up for debate, which the FDA framed, in our opinion, to lead to a very critical discussion of -181’s merits.”
The advisory panel will convene on Tuesday. The FDA is not bound by the recommendations of the panel but tend to follow them.
Social image: Nektar