With the urgency rising for abuse-deterrent opioids in an overdose-ridden world, Inspirion Delivery Sciences LLC gained a key approval and Antibe Therapeutics Inc. began work that CEO Dan Legault told BioWorld Today could help "solve this elusive problem" by providing a safer nonsteroidal inflammatory drug (NSAID) that many doctors likely would rather prescribe.
Opioids "have their own uses for neurological pain," Legault said, although "we, along with most of the world, think they are prescribed way too commonly. Part of that reason is that doctors don't have a good alternative. Not for all of their opioid prescriptions, but for a great number of them, this is a better solution."
First, the approval. Basking Ridge, N.J.-based Inspirion won the FDA's nod for oral Roxybond (oxycodone hydrochloride) tablets to treat severe pain. The abuse-deterrent formulation uses physical and chemical barriers to deter abuse without aversive agents or opioid antagonists, and represents the first immediate-release opioid analgesic cleared with labeling that describes its properties in that regard. The compound is OK'd for marketing in 5-mg, 15-mg and 30-mg dosage strengths.
Designed with Inspirion's Sentrybond technology, Roxybond includes inactive ingredients that make the tablet more difficult to manipulate for misuse and abuse even if it's subjected to physical manipulation and/or attempts at chemical extraction. Lab test data showed that, compared to another approved oxycodone immediate-release tablet, Roxybond was hard to cut, crush, grind or break using selected tools. Intact and manipulated Roxybond resisted extraction in selected household and laboratory solvents under various conditions, Inspirion said. The drug forms a viscous material that resists passage through a needle, and proves tougher to prepare for intravenous injection. Although in vitro data prove that Roxybond brings physicochemical properties expected to make abuse by injection far from easy, abuse by the intranasal, oral and I.V. routes is still possible, Inspirion conceded.
Antibe's Legault called abuse-proofing measures in general "a stop-gap, but I've never in any field of life seen some solution that smart people will get around. 'You can't crush it this way, well, crush it that way.' I'm not going to say anything bad about this approval or [about] opioids. We just think that alternative is having a safe NSAID. Doctors would clearly love that. There's room for both of these products."
Lead candidate for Antibe is ATB-346, a hydrogen sulfide (H2S)-releasing derivative of naproxen, sold as Aleve by Leverkusen, Germany-based Bayer AG. It's among the more commonly used and more cardiovascular-safe of the NSAID class.
Making news for Antibe Wednesday, though, was ATB-352, an H2S-releasing derivative of ketoprofen, a potent NSAID that also can cause trouble in the gastrointestinal (GI) system. The Toronto-based firm said it has formally commenced investigational new drug application-enabling preclinical studies. "We were into [this research] very early," Legault said. "My partner [John Wallace] first discovered how NSAIDs cause GI damage some 30 years ago. We were the first to write about the dangers of Vioxx [rofecoxib, Merck & Co. Inc.]. The world needs a safer NSAID; it has nothing to do with opioids," he said, adding that more people die because of NSAIDs than car accidents.
"We've always wanted a stronger one," he said. "We've been encouraged to do that by our medical advisers and even people in government [asking], 'Can you move faster with your second drug and help us with this opioid crisis?'" Antibe's chief scientific officer, Wallace, he added, "is one of the main guys if not the main guy" in the space. "We don't make the claim lightly" that Antibe may have cracked the NSAID code, he said, adding that he and Wallace were the "first to discover how NSAIDs cause GI damage," he said.
Kenilworth, N.J.-based Merck's Cox-2 inhibitor Vioxx for osteoarthritis and rheumatoid arthritis was voluntarily withdrawn from the market by the pharma giant. (See BioWorld Today, Oct. 28, 2004.)
WATERS NOT EASILY NAVIGATED: ANALYST
Antibe's approach, based on more than 10 years of academic and company research, allows for the linking of an NSAID molecule to a molecule releasing H2S, which is endogenously produced and functions throughout the body as an anti-inflammatory agent and signaling molecule. "We're not trying to supplant opioids when the indication clearly requires [them]," Legault said. "Our lead drug is for the general purpose market and osteoarthritis. We have extensive data, certainly the most ever published, including [data published by] all of pharma," which turned up "dramatically good" results.
The field of addiction as it relates to pain drugs is "complex," noted Piper Jaffray analyst Joshua Schimmer, whose firm hosted a conference call with an expert and issued a report Monday. Schimmer covers San Francisco-based Nektar Therapeutics Inc., which landed a phase III win in March with NKTR-181, its mu-opioid agonist tested in more than 600 patients with moderate to severe chronic low back pain who were new to opioid therapy. The trial met the primary efficacy endpoint in the SUMMIT-07 study, showing improved relief with the drug compared to placebo (p=0.0019). Key secondary endpoints of the study also were met with high statistical significance. (See BioWorld Today, March 21, 2017.)
Piper Jaffray's call "covered the various paths towards opioid addiction/abuse, the degree to which long-acting opioids have contributed to the problem (or not), and the extent to which tamper-resistant or less likeable extended-release options are able to address the unmet need," Schimmer wrote in a research report Monday. "Clearly, novel formulations/opioids are just a small part of the solution, which will require greater health care infrastructure to prevent abuse and deal with it once it emerges. Furthermore, the complexity makes measuring the real-world impact of novel formulations challenging, even as they are increasing share (led by the latest Oxycontin [oxycodone, Purdue Pharma LP] formulation)."
Nektar's NKTR-181 "might offer 'best-in-class' tamper resistance, [and] its potentially lower likeability and theoretically less addiction potential may be equally important," he said. "But claims and proof are different things." Getting a stand-out label and market perception that pushes sales "isn't easy to navigate. Add to that the complexity of managed care obstacles and it's clear that Nektar needs a highly capable partner to maximize the value of the product," in his view.