Eli Lilly Abandons Another Experimental Non-Opioid Pain Reliever

By Crystal Lindell

Eli Lilly's experimental non-opioid pain medication – named LY3857210 – had lackluster results in clinical trials, the latest setback for Big Pharma in developing alternatives to opioid analgesics.  

The pharmaceutical company told Fierce Biotech that the oral medication, which is a P2X7 inhibitor, "did not meet our high internal bar for success and is being removed from the pipeline for pain."

P2X7 inhibitors are being studied for their potential to relieve chronic pain and cancer-related pain by inhibiting inflammation and nerve signaling. 

But when Lilly tested LY3857210 in Phase 2 trials on patients with osteoarthritis and diabetic neuropathic pain, it performed no better than a placebo in relieving pain. 

The company originally purchased licensing for the drug from Asahi Kasei Pharma in 2021 for $20 million. The Japanese pharmaceutical company had already put the drug through Phase 1 testing when Eli Lilly stepped in.

Although it did not prove to be helpful for pain, Lilly said they were still exploring other uses for it.

In August of this year, Lilly also halted development of mazisotine, another non-opioid pain medication it was developing. Mazisotine blocks pain signals in peripheral nerves, but also had disappointing results in Phase 2 trials.

Lilly is still focused on finding non-opioid pain treatments. In May of this year, the company acquired SiteOne Therapeutics in a deal worth as much as $1 billion. At the time, SiteOne said it was “dedicated to the development of safe and effective pain therapeutics without the significant addiction potential and side effects of opioids.”

SiteOne had been working on a new class of non-opioid medications that target sodium channels in the peripheral nervous system to treat pain and other nerve conditions. Blocking pain signals in peripheral nerves before they reach the brain means the drug theoretically is less likely to lead to addiction or overdoses.

But that approach to pain relief has had mixed results. In August, Vertex Pharmaceuticals halted development of a drug called VX-993 after disappointing results in clinical trials.VX-993 is another non-opioid that blocks pain signals in peripheral nerves, but when given to patients recovering from bunionectomy surgery, it was only slightly more effective than a placebo.

VX-993 is similar to Journavx (suzetrigine), a non-opioid developed by Vertex that also works on peripheral nerves. Journavx was approved by the FDA in January to treat moderate to severe acute pain, despite results in clinical trials that showed it was no more effective than Vicodin.

Eli Lilly Bet $1 Billion on Non-Opioids: Will Pain Patients Pay the Price?

By Crystal Lindell

Eli Lilly is investing heavily in new non-opioid pain treatments with its latest acquisition. The pharmaceutical company announced this week that it was acquiring SiteOne Therapeutics in a deal worth as much as $1 billion. 

SiteOne describes itself as “dedicated to the development of safe and effective pain therapeutics without the significant addiction potential and side effects of opioids.” 

The company has been working on a new class of non-opioid medication that targets sodium channels in the peripheral nervous system to treat pain and other nerve conditions. Blocking pain signals in peripheral nerves before they reach the brain means the drug is unlikely to lead to addiction or overdoses.

Its drug STC-004 is in Phase 2 of clinical trials. In a February 2025 press release about the medication, SiteOne said it's an oral medication that would likely be taken once a day “for acute and chronic peripheral pain.” 

Eli Lilly said it has high hopes that STC-004 “may represent a next-generation, non-opioid treatment for patients suffering from chronic pain.” 

It’s noteworthy that Lilly doesn’t even mention acute pain, which suggests the company sees the most potential for STC-004 as a chronic pain treatment.  

While any advancement in pain treatment is obviously welcome, it seems prudent to remain skeptical of any company touting a new medication because its a “non-opioid.”

Vertex Pharmaceuticals recently won FDA approval for Journavx (suzetrigine) a non-opioid that also blocks pain signals in the peripheral nervous system. The FDA approved Journavx for acute pain only, despite lackluster results in clinical trials showing that it works no better than a low dose of hydrocodone.

There’s been a gold rush over the last decade by Vertex, Lilly and other pharmaceutical companies hoping to cash in on the opioid-phobia that resulted from the 2016 CDC opioid guidelines. But it remains unclear if it will just result in fool’s gold for pain patients desperate for relief. 

Mark Mintun, VP of Neuroscience Research and Development for Lilly, admits that thus far “effective non-opioid treatment remains elusive.”

According to one estimate, the global chronic pain market was worth over $72 billion in 2024 and is projected to grow to $115 billion by 2031.

With so much money on the line for any company that even partially succeeds in developing new pain relievers, resources are going to keep pouring into these non-opioid alternatives, regardless of how effective they actually are. 

The sad fact is that there just isn’t as much money in reliable, well-researched generic opioid medications like morphine, which are vastly cheaper than the non-opioids being developed to replace them. 

For chronic pain patients, the $1 billion that Eli Lilly used to acquire SiteOne would be more beneficial if it was spent on lobbying the government and medical professionals to expand access to opioid pain relievers. 

While my hope is that these types of opioid alternatives will deliver on their promises — my fear is that patients will eventually be forced onto them, even if they don't work nearly as well as opioids.

New Non-Opioid Analgesic Gets Priority Review from FDA

By Pat Anson

The Food and Drug Administration could approve an experimental non-opioid analgesic early next year, potentially making it the first new medication for acute pain in over two decades.

Vertex Pharmaceuticals says the FDA has accepted its New Drug Application for suzetrigine, giving the drug a priority review with a target action date of January 30, 2025. Suzetrigine has previously been granted FDA Fast Track and Breakthrough Therapy designations for the treatment of moderate-to-severe acute pain.

“Today’s FDA filing acceptance for suzetrigine marks a critical milestone toward bringing this new, transformative non-opioid analgesic to the millions of patients,” Nia Tatsis, PhD, an Executive Vice President and Chief Regulatory and Quality Officer for Vertex, said in a statement.

“The FDA’s granting of a priority review further reinforces the high unmet need in treating acute pain, and the filing brings us one step closer to our objective of filling the gap between medicines with good tolerability but limited efficacy and opioid medicines with therapeutic efficacy but known risks, including addictive potential.”

Suzetrigine is designed to block pain in the peripheral nervous system, rather than the brain. That means it won’t have the “liking” effects of opioids or be as addictive.  

In Phase 3 clinical studies, suzetrigine was more effective in reducing post-operative pain than a placebo after minimally invasive surgeries.  Over 80% of patients rated suzetrigine as good or excellent in treating acute pain, but it was not more effective than a combination of the opioid hydrocodone and acetaminophen, more commonly known as Vicodin.

Vertex hopes suzetrigine will eventually be approved for a variety of pain conditions, not just post-operative pain.  The company has been studying the drug as a treatment for pain caused by diabetic peripheral neuropathy.

“In my 24 years practicing medicine, I have seen firsthand the desperate need for new non-opioid therapies for treating pain. Too many people today are either undertreated, dealing with negative side effects of currently available therapies or foregoing pain medications altogether for fear of becoming dependent on opioids,” said Scott Weiner, MD, a Vertex consultant and Associate Professor of Emergency Medicine at Harvard Medical School.

The Biden Administration has been under pressure from lobbyists, politicians and anti-opioid activists to have the FDA approve more non-opioid medications like suzetrigine. The new analgesics are expected to be far more expensive than opioids and other older pain relievers.

If the FDA approves suzetrigine in January, it will coincide with implementation of the NOPAIN Act, which will expand access to non-opioid analgesics in outpatient surgical settings by making them eligible for higher Medicare reimbursement rates.