I recently wrote how Antibe's experimental analgesic/anti-inflammatory drug, otenaproxesul, something that would represent a quantum leap in chronic pain management, ran into quite a snag (See A Bad Day For Antibe, And Pain Patients). After earlier trials showed an intriguing safety and efficacy profile – NSAID-like pain relief without the associated GI and kidney toxicity –an unexpected problem showed up: Liver toxicity. While this is a well-known and serious safety concern for Tylenol, it is rarely seen with NSAID use. But, Antibe got an unfortunate lesson that those of us with experience in drug discovery research know all too well: something always screws up, in this case, elevated liver enzymes, something you do not want to see in a drug that is meant to be taken chronically.
The company must have decided that there was no fixing this because it just announced that it was changing course, something that is rarely a good sign. Antibe will now attempt to develop otenaproxesul to treat acute short-term postoperative pain, something that opioid analgesics handle well in most cases.
"Otenaproxesul targets urgent need to reduce opioid prescriptions"
Uh oh. Having failed to develop a badly needed drug for safe, long-term relief from pain and inflammation, the company seems to be hopping on the anti-opioid bandwagon, something I have written extensively about (1). This is not to say that otenaproxesul will necessarily go to the giant pharmacy in the sky, but this announcement is not good news.
It is not terribly surprising that otenaproxesul hit the wall. Since heroin and aspirin were invented in the 19th century, there has been very little progress in pain control, and not from the lack of effort; this is a tough nut to crack. Still, Antibe continues to be (or act) optimistic about otenaproxesul's potential:
“In our comprehensive review, it became apparent that otenaproxesul’s remarkable potency, GI protection and overall safety profile should be leveraged for acute pain use”
I wish them well. Not everyone can tolerate opioids, which, despite their unmatched potential to control severe pain, do have side effects, primarily nausea and vomiting (2). And based on the number of studies that still aim to replace post-op opioid treatment – something that is still all the rage these days – patients can hardly be assured of getting adequate pain relief in the hospital (3). So, if Antibe succeeds with its new plan, otenaproxesul's utility will still be substantial, just not the miracle that all of us with aches and pain were hoping for.
"Lead drug, otenaproxesul, ideally suited for US$13 billion post-operative pain market."
Wishful thinking? We shall see.
DISCLAIMER: My IRA contains an embarrassing (bordering on pitifully) small amount of Antibe stock. Jeff Bezos has little to worry about.
NOTES
(1) See 'Advil As A Substitute For Opioids? NY Times' Gina Kolata 'Busts' One Myth With Another,' and 'Tylenol Isn't So Safe, But At Least It Works, Right?' Also, see 'The Opioid Crisis (Updated): 100 Articles & Published Op-Eds .'
(2) Note that I have not included addiction. The chance of a surgery patient becoming addicted from a few days worth of oxycodone following an operation is close to zero.
(3) See 'Florida Officials Successfully Withheld Pain Meds From Surgical Patients. Aren't They Special?'
Josh Bloom
Director of Chemical and Pharmaceutical Science
Dr. Josh Bloom, the Director of Chemical and Pharmaceutical Science, comes from the world of drug discovery, where he did research for more than 20 years. He holds a Ph.D. in chemistry.
