FDA panel rejects Nektar's opioid analgesic NKTR-181 citing safety concerns, lack of data

A panel of FDA advisors voted 27-0 Tuesday against approval of Nektar Therapeutics' opioid pain drug NKTR-181, also known as oxycodegol, sending company shares down as much as 14.5%. In response to the vote, Nektar said it has decided to withdraw the marketing application, which sought approval of the therapy to manage chronic low back pain in adults with pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative options are inadequate. 

At the meeting, the advisory committee cited concerns about the drug being misused or abused, the lack of data to determine the possible abuse when snorted or injected, and the potential for liver toxicity. "Just too much (data) was missing…I couldn't say the benefits outweighed the risks," commented panel member Lee Hoffer. Meanwhile, Sherif Zaafran voted against approval "even though I liked the idea of what they are trying to do," but he found that "the data, I don't think at the end of the day, [were] sufficient from the standpoint of efficacy and safety." 

The FDA was initially expected to decide whether to approve NKTR-181 by August 29 last year, but Nektar said a final decision was delayed as the agency conducted a review into how it evaluates new drug applications for the drug class. Nektar also announced Tuesday that it will make no further investment in the NKTR-181 programme, leading to cost savings of between $75 million and $125 million this year.

According to Nektar, NKTR-181 is the first full mu-opioid agonist molecule designed to provide potent pain relief, but "without the high levels of euphoria that can lead to abuse and addiction with standard opioids." The company added that compared to commercially available opioids, the more gradual effects of NKTR-181 may make it less tempting as a drug of abuse. It has also said that if snorted or injected, the rate of the drug's entry into the brain would be similar to when the treatments are taken orally.  

In May last year, Nektar announced the launch of its Inheris Biopharma subsidiary, a central nervous system (CNS)-focused company that would be responsible for commercialising NKTR-181, as well as developing other CNS programmes. At the time, CEO Howard Robin stated that the move would allow "Nektar to remain focused on advancing our immuno-oncology and immunology development pipeline," which includes bempegaldesleukin, a CD122-preferential IL-2 pathway agonist formerly known as NKTR-214 that the company is developing for multiple cancer types. 

For related analysis, see ViewPoints: NKTR-181 nearing round-trip from afterthought to breakthrough and back? See also ViewPoints: Nektar feeling the heat on FDA opioid crackdown.

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